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Purpose: Insulinomas are the most common functioning neuroendocrine neoplasms of the pancreas, typically diagnosed due to characteristic symptoms. In the vast majority, the treatment is surgical and curative, requiring accurate localization of the tumour; conventional imaging, including somatostatin receptor molecular imaging, is negative in up to 10 % of cases. Recently, labelled glucagon-like peptide receptor (GLP-1R) analogues were introduced as a sensitive diagnostic method for localization of insulinomas. The aim of this study was to assess the diagnostic accuracy of a Tc-99m-labelled GLP-1R agonist [Lys 40 (AhxHYNIC-[ 99m Tc]EDDA)NH 2 ]-exendin-4 for localization of occult insulinoma., Procedures: Eight patients (all females; age range 35-75 years) with biochemically proven insulinoma and with negative or inconclusive conventional imaging (consisting of somatostatin receptor scintigraphy, computed tomography, endoscopic ultrasound and magnetic resonance imaging) were enrolled. Whole-body single-photon emission tomography/computed tomography (SPECT/CT) imaging was performed 4 h post-injection of 740 MBq of [Lys 40 (AhxHYNIC-[ 99m Tc]EDDA)NH 2 ]-exendin-4. Surgical treatment was performed based on imaging findings. Histology of the removed lesions and biochemical and clinical symptom resolution was considered as the gold standard for analysis of the imaging results., Results: Focal uptake of [Lys 40 (AhxHYNIC-[ 99m Tc]EDDA)NH 2 ]-exendin-4 was found in all patients, leading to successful removal of the offending lesion and complete biochemical and symptomatic resolution. Histological analysis confirmed insulinoma in all included patients., Conclusions: [Lys 40 (AhxHYNIC-[ 99m Tc]EDDA)NH 2 ]-exendin-4 SPECT/CT appears to be an excellent molecular imaging method for preoperative localization of an occult insulinoma, surpassing conventional imaging methods. If routinely available, it could be considered as a method of choice due to its favorable combination of imaging characteristics.

Five thiosemicarbazones (H 2 L n ) derived from 4,6-diacetylresorcinol (n = 1-4) and salicylaldehyde (n = 5) have been synthesized and spectroscopically characterized. Single crystal X-ray diffraction studies on some of them show that the molecular structure is dominated by intramolecular hydrogen bonds involving the O(1)-H group of the resorcinol/salicylaldehyde group and the azomethinic nitrogen atom and sulfur atom of the thiosemicarbazone arm. All of the ligands react with fac-[ReBr(CO) 3 (CH 3 CN) 2 ] in the presence of NEt 3 to form the stable anionic complexes [NHEt 3 ][fac-[Re(L n )(CO) 3 ] (1-5). The thiosemicarbazonate ligand, as suggested by spectroscopic data and confirmed by X-ray diffraction, acts as a tridentate S,N,O system. The complexes are stable in solution for weeks, although other dimeric species were also detected by X-ray diffraction analysis. The reaction of fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + with the appropriate ligand at 100 °C for 30 min yielded the complexes [fac-[ 99m Tc(L n )(CO) 3 ] - (Tc1-Tc5). The radiochemical yield and purity were determined by HPLC and their chemical identity was ascertained by comparing their radiochromatogram with the chromatogram of the rhenium congeners (1-5). The results of biodistribution studies in mice on the five technetium compounds showed rapid blood clearance and fast liver uptake that slowly cleared into the intestines, a finding that indicates the hepatobiliary tract as the major excretory pathway. HPLC analysis of urine and blood serum samples from mice injected with the 99m Tc complexes confirmed their in vivo stability since the predominant radiochemical species had the same retention time as the corresponding injected compound., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Despite recent technological advances allowing for quantitative single-photon emission computed tomography (SPECT), quantitative SPECT has not been widely used in the clinical practice of osteoporosis. The aim of this study is to evaluate the feasibility of quantitative bone SPECT/CT for measuring lumbar standard uptake value (SUV) in patients with different bone-mineral density (BMD), and investigate the correlation between SUV measured with 99m Tc-methylene diphosphonate (MDP) SPECT/CT and BMD assessment by dual-energy X-ray absorptiometry (DXA)., Methods: A retrospective analysis of 62 cases 99m Tc-MDP whole-body bone imaging and local lumbar SPECT/CT tomography were performed. According to the results of dual-energy X-ray bone density examination, they were divided into normal group, osteopenic group, and osteoporosis group. The raw SPECT data were reconstructed using flash3D which includes attenuation correction, scatter compensation, and collimator resolution recovery, SPECT images from this algorithm were calibrated for SUV analysis. Comparing difference of lumbar SUV in different BMD subjects, and investigating the correlation between lumbar SUV and BMD. Data were analyzed by one-way ANOVA and Pearson regression analysis using SPSS 17.0 software., Results: The maximum SUV (SUV max ) and mean SUV (SUV mean ) of L1-L4 vertebral in 62 subjects were 7.39 ± 1.84 and 4.90 ± 1.27, respectively. The average BMD was 0.85 ± 0.15 (g/cm 2 ), and the average CT value was 145.88 ± 53.99 (HU). The SUV max , SUV mean , BMD, and CT values of the lumbar spine were statistically significantly different among the three groups (F = 24.089, 30.501, 94.847, 30.241, all p < 0.001), and the osteopenic group was significantly lower than the normal group (all p < 0.001), the osteoporosis group was significantly lower than the normal group and the osteopenic group (all p < 0.001). Lumbar SUV max , SUV mean , and BMD were significantly negatively correlated with age (r = - 0.328 to - 0.442, all p < 0.05), and positively correlated with body weight and CT value (r = 0.299-0.737, all p < 0.05), but no significant correlation with height (r = 0.006-0.175, all p > 0.05). Lumbar SUV max and SUV mean increased significantly with the increase of BMD (r = 0.638, 0.632, p < 0.001)., Conclusion: The SUV of lumbar spine in 99m Tc-MDP bone SPECT/CT was significantly different among subjects with different BMD, and the SUV was positively correlated with BMD. These findings justify that quantitative bone SPECT/CT is an applicable tool for clinical quantification of bone metabolism in osteoporosis patients.

Purposes: Senescence is an inevitable and irreversible process, which may lead to loss in muscle and bone density, decline in brain volume and loss in renal clearance. Although aging is a well-known process, few studies on the consumption of nanodrugs by elderly people were performed., Methods: We evaluated three different nanosystems: i) carbon based nanosystem (Graphene Quantum Dots, GQD), ii) polymeric nanoparticles and mesoporous silica (magnetic core mesoporous silica, MMSN). In previous studies, our group has already characterized GQD and MMSN nanoparticles by dynamic light scattering analysis, atomic force microscopy, transmission electron microscopy, X-ray diffraction, Raman analysis, fluorescence and absorbance. The polymeric nanoparticle has been characterized by AFM and DLS. All the nanosystems were radiolabeled with 99 m-Tc by. The in vivo biodistribution/tissue deposition analysis evaluation was done using elder (PN270) and young (PN90) mice injected with radioactive nanosystems., Results: The nanosystems used in this study were well-formed as the radiolabeling processes were stable. Biodistribution analysis showed that there is a decrease in the uptake of the nanoparticles in elder mice when compared to young mice, showing that is necessary to increase the initial dose in elder people to achieve the same concentration when compared to young animals., Conclusion: The discrepancy on tissue distribution of nanosystems between young and elder individuals must be monitored, as the therapeutic effect will be different in the groups. Noteworthy, this data is an alarm that some specific conditions must be evaluated before commercialization of nano-drugs. Graphical Abstract Changes between younger and elderly individuals are undoubtedly, especially in drug tissue deposition, biodistribution and pharmacokinetics. The same thought should be applied to nanoparticles. A comprehensive analysis on how age discrepancy change the biological behavior of nanoparticles has been performed.

Recent developments in sentinel lymph node (SLN) and radio occult lesion localization (ROLL) highlight the need for a multimodal contrast agent, providing better presurgical PET imaging and improved intraoperative mapping thanks to fluorescence detection. For this reason, we have studied a trimodal SLN/ROLL targeting agent ( 99m Tc- 68 Ga-ICG) with commercially available kits of macroaggregated or nanocolloidal albumin (MA/NC-HSA). 68 Ga PET imaging does provide better spatial resolution and makes it possible to predict signal intensity during surgery. The presence of 99m Tc assesses the efficacy of these compounds in vitro and also during the surgery procedure. The aim of this study was to optimise the labelling and tagging of these two radiopharmaceuticals and assess their yields and stability. Kits of MA/NC-HSA particles (Pulmocis® and NanoAlbumon®) were used for sequential radiolabelling with 99m Tc and 68 Ga. Fluorescent tagging was performed using indocyanine green, a tricarbocyanine dye. The ITLC radiochemical purity of the trilabelled MA/NC-HSA was >95%. Fluorescent purity was measured by scanning the strips with a PhotoDynamicEye probe. Finally, in vitro stability tests, performed with DTPA and human serum solutions, assessed the efficacy of fluorescent tagging and radiolabelling., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Marco Giovanni Persico et al.)

Since its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)-ligand PET has demonstrated great potential. PSMA-ligand imaging is increasingly influencing therapeutic decision making, although its impact on patient outcomes still needs to be defined. One relatively new application, enabled through chemical and engineering efforts, is PSMA-guided surgery. This review highlights the potential of PSMA-guided surgery and discusses its implications in lymph node dissection in primary and recurrent prostate cancer., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Radiation-induced DNA damage occurs from direct and indirect effects. The induction is influenced by the physical characteristics of the radionuclide, especially its linear energy transfer. Hypoxia reduces the effect of irradiation treatment in tumor cells and leads to poor patient outcomes. High linear energy transfer emitters can overcome this obstacle. Our aim is to demonstrate the influence of hypoxia on the interaction of different radiation qualities with isolated DNA., Methods: PuC19 Plasmid DNA was irradiated with 223 Ra, 188 Re, 99m Tc and 99m Tc-labeled pyrene with and without DMSO under hypoxia or normoxic conditions. DNA damages in form of single-(SSB) and double-strand breaks (DSB) were analyzed by gel electrophoresis., Results: Radiation doses up to 200 Gy of 223 Ra, 188 Re and 99m Tc led to maximal yields of 80% SSB and 30%, 28% and 32% DSB, respectively. Hypoxia had minor effects on damages from 223 Ra, but caused a small enhancement in DSB for 188 Re and 99m Tc. DMSO prevented DSB completely and reduced SSB from the "free" radionuclides to comparable levels. DNA-binding 99m Tc-labeled pyrene induced less SSB and DSB compared to [ 99m Tc]TcO 4 - . However, the incubation with DMSO could prevent the SSB and DSB induction only to a minor extent., Conclusions: Hypoxia does not limit DNA damage induced by 223 Ra, 188 Re, 99m Tc and 99m Tc-labeled pyrene. Dose-dependent radiation effects were comparable for alpha-emitters and both high- and low-energy electron emitters. The radioprotection by DMSO was not influenced by hypoxia. The results indicate the contribution of mainly indirect radiation effects for 99m Tc, 188 Re and 223 Ra. 99m Tc-labeled pyrene caused direct DNA damages and Auger-electrons from 99m Tc-labeled pyrene are more effective than high-energy electrons or alpha particles., Advances in Knowledge: Without the consideration of DNA repair mechanisms, oxygen has no direct influence in radiation-induced DNA damages by different radiation qualities., Implications for Patient Care: The short-time stimulation with oxygen during patient radiation could have minor influence compared to constant oxygen flooding to overcome hypoxic barriers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The quantitative accuracy and image quality of multi-isotope SPECT is affected by various hardware-related perturbations. The present study evaluates the simultaneous acquisition of multiple isotopes using a multiplexed multi-pinhole SPECT system, assesses the extent of different error sources, and proposes experimental procedures for its objective characterization. Methods: Phantom measurements with single-, dual- and triple-isotope combinations of 99m Tc, 111 In, 123 I, 177 Lu, and 201 Tl were performed with the NanoSPECT/CT PLUS to evaluate system energy resolution, count rate performance, sensitivity, collimator penetration, hardware versus object scatter, spectral crosstalk, spatial resolution, spatial registration accuracy, image uniformity, image noise, and image quality. Results: The intrinsic detector properties were suitable for the simultaneous acquisition of up to 3 isotopes with limitations for count rates exceeding 104 kcps and γ-energies lower than 75 keV. Spectral crosstalk between isotopes was more likely mediated by hardware than by source scatter and was strongly dependent on the isotope combination. Simultaneous multi-isotope acquisitions slightly degraded spatial resolution and image uniformity for spatially superimposed but not for spatially separated activity distributions while the background noise level was increased for all multi-isotope studies. For particular isotopes, collimator penetration and x-ray fluorescence contributed a significant portion of error. Conclusion: The NanoSPECT/CT PLUS enables the simultaneous acquisition of 3 radioisotopes with high quantitative accuracy and only little loss of image quality when the activity ratio is adapted to isotope-specific count rate sensitivities and when the system calibration is performed with phantoms of appropriate size., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Lung cancer is among the most common cancers worldwide, responsible for 13% of all new cancer cases. Also, it is the leading cause of cancer death among both men and women. In this scenario, an effective and efficient treatment is required., Objective: Production of two gold nanoparticles: 198Au and 99mTc-Au. The first one has been produced from irradiation of the 197Au in order to produce a beta-emitter gold nanoparticle for cancer therapy. The second one has been produced from the radiolabeling of gold nanoparticles with technetium 99 metastable in order to produce imaging nanoagent., Methods: The 198Au nanoparticles were produced by irradiation and identified by hyper-purity germanium (HPGe). They were then evaluated in vitro in order to confirm the behavior on cell proliferation of lung cancer cell lines by the MTT methodology using A549 cells. The 99mTc-Au nanoparticles were produced by directradiolabeling with 99mTc and evaluated in vivo as intralesional nanoagent., Results: The results showed that in both cases, all the nanoparticles have performed their duties with excellence. The 198Au nanoparticles were capable to kill lung cancer cells, while 99mTc-Au was capable to image the tumor after intralesional injection. In addition, 99mTc-Au nanoparticles were useful for biodistribution assay imaging, showing the main organs responsible for the nanoparticle uptake in healthy animals., Conclusion: Both gold nanoparticles showed to be a highly efficient nanoagent for both: therapy and diagnosing of lung cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Few nuclear reactors in the world producing high specific activity (HSA) 99Mo using enriched 235U (HEU), are aging and are planned for shut down in the near future. Further, HEU will not be freely available, due to safeguards, and the technology for 99Mo from low-enriched 235U (LEU) is not yet widely accepted since 239Pu contamination in the product is an issue. Production of 99mTc from low specific activity (LSA) 99Mo obtained from 98Mo(n,)99Mo reaction in research reactor and 100Mo(,n)99Mo reaction in accelerator or directly from 100Mo(p,2n)99mTc nuclear reaction in cyclotron, has been explored [1]. The methyl ethyl ketone (MEK) based solvent extraction technique is n well known method for the separation of 99mTc from low specific activity 99Mo. The 99Mo/99mTc autosolex generator [2], a computer controlled automated module, utilizes the conventional MEK solvent extraction method for extraction of 99mTc. Herein, we have validated the usage of autosolex for preparation of pharmacopoeia grade 99mTcO4- from 7.40-27.5 GBq of LSA 99Mo-SodiumMolybdate (99MoO42-) solution and validated the quality of the 99mTcO4- by preparing wide range of 99mTc-radiopharmaceuticals (99mTc-RP)., Materials and Methods: The 99mTcO4- was extracted from the autosolex as described in [2] starting from 7.40-27.5 GBq of LSA 99MoO42- and subjected to the required physico-chemical and biological quality control (QC) tests. The eluted 99mTcO4- labeled various fourth generation 99mTc radiopharmaceuticals cold kits (99mTc-cold kits) apart from regular 99mTc-cold kits in our centre. Various 99mTc-RP extracted 99mTcO4- using standard procedures [3] were prepared and subjected to required QC as Indian Pharmacopeia monograph [4] and used in scintigraphic imaging in patients. The radiation exposure dose to the operator were compared between autosolex and manual MEK based solvent extraction generator., Results: The extracted 99mTcO4- from autosolex is a clear and colorless solution with pH between 5.0-6.5. The elemental molybdenum (Mo) and aluminum (Al) content <10µg/mL, MEK levels <0.1%, 99Mo breakthrough <0.030% and radiochemical purity (RCP) >98%. All the extracted 99mTcO4- batches complies sterility test, endotoxin limit (EL) <5EU/mL. The RCP of all the labeled 99mTc-RP >95%. The autosolex delivers much less radiation dose to the operator than the convention manually handled MEK based solvent extraction generator., Conclusions: Autosolex Generator was successfully used to obtain pharmaceutical grade 99mTcO4- from LSA 99MoO42- and generator is safe in radiological and pharmacological point of view. The suitability of the autosolex for use in hospital radiopharmacy was shown by using the 99mTcO4- to prepare various 99mTc-RP and using these 99mTc-RP for scintigraphic imaging in patients.

Introduction: Prostate cancer is a serious threat to men's health so it is necessary to develop technics for early detection of this malignancy. The purpose of this research was the evaluation of a new 99m Tc-labeled GnRH analogue as an imaging probe for tumor targeting of prostate cancer., Methods: 99m Tc-labeled-DLys6-GnRH analogue was prepared based on HYNIC as a chelating agent and tricine/ EDDA as coligands for labeling with 99m Tc. HYNIC was coupled to epsilon amino group of DLys6 through aminobutyric acid (GABA) as a linker. Radiochemical purity and stability in normal saline and serum, were determined by TLC and HPLC methods. Furthermore, calculation of protein-binding and partition coefficient constant were carried out for 99m Tc labeled peptide. The cellular experiments including receptor binding specificity and affinity were studied using three prostate cancer cell lines LN-CaP, DU-145 and PC-3. Finally, the animal assessment and SPECT imaging of radiolabeled GnRH analogue were evaluated on normal mice and nude mice bearing LN-CaP tumor., Results: The GnRH conjugate was labeled with high radiochemical purity (~97%). The radiolabeled peptide showed efficient stability in the presence of normal saline and human serum. The in vitro cellular assays on three prostate cancer cell lines indicated that the radiotracer was bound to LN-CaP cells with higher affinity compared to DU-145 and PC-3 cells. The Kd values of 99m Tc- HYNIC (tricine/ EDDA)-Gaba-D-Lys6GnRH were 89.39±26.71, 93.57±30.49 and107.3±18.82 in LN-CaP, PC-3 and DU-145 cells respectively. The biodistribution studies in normal mice and LN-CaP tumor-bearing nude mice showed similar results including rapid blood clearance and low radioactivity accumulation in non-target organs. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor uptake was 1.72±0.45 %ID/g at 1h p.i. decreasing to 0.70±0.06%ID/g at 4h p.i. for 99m Tc-HYNIC-Gaba-D-Lys6GnRH. The maximum tumor/ muscle ratio was 2.30 at 1h p.i. Pre-saturation of receptor using an excess of unlabeled peptide revealed that the tumor uptake was receptor mediated. The results of the SPECT image of LN-CaP tumor were in agreement with the biodistribution data., Conclusion: Based on this study, we suggest LN-CaP as a favorable cell line for in vivo studies on GnRH analogues. Moreover, this report shows that 99m Tc-HYNIC (tricine/EDDA)-Gaba-D-Lys6GnRH may be a suitable candidate for further evaluation of prostate cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It has been reported that dysregulation of microRNA-155 expression and function is associated with tumorigenesis, growth, tumor subtypes, invasion, and poor survival rates. Peptide nucleic acid (PNA), an artificially synthesized nucleic acid mimic, has been applied for molecular diagnosis. In this study, a PNA sequence that undergoes complementary binding to miR-155 was labeled with 99m Tc to evaluate whether the tracer could visualize the expression of miR-155 in breast cancer. Both antisense PNA (anti-PNA, fully complementary bound to human mature miR-155 , referred to as "anti-PNA-155") and mismatched PNA (referred to as "mis-PNA") single strands containing 23-mer were synthesized. The relative expression of miR-155 in MCF-7 cells and tumors was higher than that in MDA-MB-231 cells and tumors. Single-photon emission computed tomography (SPECT) scan showed that radioactivity mainly accumulated in kidney. MCF-7 tumors, but not MDA-MB-231 tumors, were clearly visualized after [ 99m Tc]anti-PNA-155 injection. MCF-7 tumors were less visible when coinjected with 100-fold excess of anti-PNA-155 or injected with [ 99m Tc]mis-PNA, which suggested specific binding. Biodistribution study results were consistent with SPECT imaging. We successfully demonstrated that [ 99m Tc]anti-PNA-155 could visualize miR-155 expression in vivo, suggesting it may be a promising probe applied in breast cancer.

Development of a complex based on iron oxide nanoparticles (IONPs) for diagnosis and dual magnetic hyperthermia/radionuclide cancer therapy accomplishing high yields of radiolabeling and great magnetic heat induction is still a challenge. We report here the synthesis of citric acid, poly(acrylic acid) (PAA) and poly(ethylene glycol) coated IONPs and their labeling with three radionuclides, namely, technetium ( 99m Tc), yttrium ( 90 Y), and lutetium ( 177 Lu), aiming at potential use in cancer diagnosis and therapy. Polyol-synthesized IONPs are a flowerlike structure with 13.5 nm spherically shaped cores and 24.8 nm diameter. PAA-coated nanoparticles (PAA@IONP) showed the best characteristics such as easy radiolabeling with very high yields (>97.5%) with all three radionuclides, and excellent in vitro stabilities with less than 10% of radionuclides detaching after 24 h. Heating ability of PAA@IONP in an alternating external magnetic field showed intrinsic loss power value of 7.3 nH m 2 /kg, which is one of higher reported values. Additionally, PAA@IONP itself presented no significant cytotoxicity to the CT-26 cancer cells, reaching IC50 at 60 μg/mL. However, under the external magnetic field, they show hyperthermia-mediated cells killing, which correlated with the magnetic field strength and time of exposure. Since PAA@IONP are easy to prepare, biocompatible, and with excellent magnetic heat induction, these nanoparticles radiolabeled with high-energy beta emitters 90 Y and 177 Lu have valuable potential as agent for dual magnetic hyperthermia/radionuclide therapy, while radiolabeled with 99m Tc could be used in diagnostic imaging.

The clinical impact and accessibility of 99m Tc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5-Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5-Fluorouracil was synthesized as (1-[{1'-(1''-deoxy-2'',3'':4'',5''-di-O-isopropylidene-β-D-fructopyranose-1''-yl)-1'H-1',2', 3'-triazol-4'-yl}methyl]-5-fluorouracil) (E) and radiolabeled with 99m Tc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell-binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF-5 cells. The radiochemical purity of the [ 99m Tc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF-7 cells than HaCaT cells. IC 50 values of E were found 31.5 ± 3.4 μM and 20.7 ± 2.77 μM for MCF-7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99m Tc has selective for breast cancer cells., (© 2019 John Wiley & Sons, Ltd.)

Objective: Differentiation of infection from aseptic inflammation represents a major clinical issue. None of the commercially available compounds (labeled granulocytes, antigranulocyte antibodies, Ga-citrate, labeled immunoglobulin G, F-FDG) is capable of this differentiation, producing a nonnegligible false-positive rate. Recently, our group reported on a reliable labeling procedure of the antimicrobial peptide human β-defensin 3 (HBD-3) with Tc. The aim of this study was to evaluate in vivo Tc-HBD-3 uptake in a rat model of infection., Methods: Recombinant HBD-3 was radiolabeled with Tc. Radiolabeling yield and specific activity of the compound were calculated. Chromatographic behavior and biological activity of Tc-HBD-3 were also assessed. An experimental model involving Staphylococcus aureus-induced infection and carrageenan-induced aseptic inflammation was performed in 5 Wistar rats. Serial planar scintigraphic acquisitions were performed from 15 to 180 minutes after Tc-HBD-3 intravenous administration. Radiotracer uptake was evaluated qualitatively and semiquantitatively as a target-to-nontarget ratio., Results: Radiolabeling yield of Tc-HBD-3 was 70% with a specific activity of 6 to 8 MBq/μg. A significant and progressive Tc-HBD-3 uptake was observed in the site of S. aureus-induced infection, with a maximum average target-to-nontarget ratio of 5.7-fold higher in the infection site compared with an inflammation site observed at 140 minutes., Conclusions: In vivo imaging with Tc-HBD-3 in a rat model of S. aureus-induced infection demonstrated favorable uptake in the infection site compared with sterile inflammation and background. These promising results, together with previous ex vivo uptake and toxicity assessment, suggest the potential of Tc-HBD-3 as a novel agent for specific infection imaging.

Objectives: The epidermal growth factor receptor (EGFR) signaling pathway is widely recognized to play an important role in development and progression of many malignant tumors, including lung cancer. The aim of this study was to produce a useful technetium-99m ( 99m Tc) complex for early detection and staging of EGFR-positive tumors. Methods: The authors labeled quinazoline derivative (3-iodinephenyl) quinazoline-4, 6-diamine with 99m Tc using S-acetylmercaptoacetyltriglyglycinate (MAG 3 ) conjugated to quinazoline derivative through 4-[(2-aminoethyl)amino]-4-oxobut-2-enoic acid because it is a bifunctional chelator with an average yield of 93.9% ± 2.5% and radiochemical purity of >98%. Results: In vitro studies indicate that the [ 99m Tc]-complex 13 has high stability in physiological conditions and binds the HCC 827 cells and shows HCC 827 internalization. The biodistribution of the [ 99m Tc]-complex 13 in healthy Institute of Cancer Research mice indicates the rather fast blood clearance through the hepatobiliary system. Conclusion: These preliminary results pave the road for estimating the status of EGFR and monitoring the response to EGFR tyrosine kinase inhibitors as a personalized cancer therapy regimen.

Development of tumor dual mode contrast agents is still a great challenge due to the relative low accumulation at tumor site, which result in the poor imaging efficiency. In this study, we constructed functional technetium-99m ( 99m Tc) labeled polyethylenimine (PEI)-entrapped gold nanoparticles (Au PENs) with pH-responsive charge conversion property for enhanced single photon emission computed tomography (SPECT)/computed tomography (CT) dual mode imaging of cancer cells. PEI with amine functional groups (PEI.NH 2 ) was successively modified with monomethyl ether and carboxyl functionalized polyethylene glycol ( m PEG-COOH), maleimide and succinimidyl valerate functionalized PEG (MAL-PEG-SVA), diethylenetriaminepentaacetic dianhydride (DTPA), and fluorescein isothiocyanate (FI), and used to entrapped gold nanoparticles inside, followed by conjugation with the alkoxyphenyl acylsulfonamide (APAS) through the PEG maleimide, acetylation of the PEI leftover surface amines and 99m Tc labeling. The created nanosystem with the mean Au core diameter of 3.3 nm and with a narrow size distribution displays an excellent colloidal stability and desired cytocompatibility in the investigated Au concentration range. Due to the fact that the attached APAS moieties are responsive to pH, the functionalized Au PENs with a neutral surface charge can switch to be positively charged under slightly acidic pH condition, which could improve the cellular uptake by cancer cells. With these properties, the developed functionalized Au PENs could achieve enhanced dual mode SPECT/CT imaging of cancer cells in vitro. The constructed PEI-based nanodevices may be adopted as an excellent dual mode contrast agent for SPECT/CT imaging of cancer cells of different types.

Background: 99m Tc-Rituximab is a new specific radiopharmaceutical that binds to the CD20 receptor which is highly expressed on the surface of B cells. We conducted a study in which 99m Tc-Rituximab was compared with filtered 99m Tc-sulfur colloid (fTcSC) for sentinel lymph node (SLN) detection in patients with breast cancer., Method: The study is divided into three parts. 1. Initially, 25 patients were selected for an internal controlled trial to received both 99m Tc-Rituximab and fTcSC, the interval time is separated by ≥2 days. 2. Then, 91 patients were selected for a randomized controlled trial (41 and 50 patients in the 99m Tc-Rituximab and fTcSC groups, respectively). All patients were administered either agent at the 6- and 12-o' clock positions by subareolar injection technique. SLN mapping was then performed 2 h after injection. 3. Serial dynamic images were further acquired for 2 h in 31 patients (22 and 9 patients from 99m Tc-Rituximab and fTcSC cohorts, respectively)., Results: The identification rate of lymphoscintigraphy and SLNB in all and axilla regions for 99m Tc-Rituximab and 99m Tc-SC were 98.5% vs 98.7, 100% vs 98.4%, respectively. The mean number of SLNs identified by 99m Tc-Rituximab and fTcSC was respectively 2.72 and 3.28, with a significant difference of P = 0.013 (paired sample t-test). The difference exists in the internal mammary and clavicular area, not in the axillary. The mean number of axillary sentinel lymph node biopsy (SLNB) for 99m Tc-Rituximab and fTcSC was 2.95 vs 3.14, respectively, and no significant difference existed. 99m Tc-Rituximab also exhibited a significantly faster injection site clearance rate when compared with fTcSC (0.193 ± 0.057 h - 1 vs 0.021 ± 0.007 h - 1 , respectively)., Conclusion: No significant difference was observed in identification rate and number of axillary SLN imaging and SLNB, between the two tracers. Compared to fTcSC, 99m Tc-Rituximab based imaging demonstrated a fewer number of secondary lymph nodes and had faster injection site clearance rate., Trial Registration: www.chictr.org.cn, ChiCTR1900024990 (retrospectively registered August 6, 2019).

More than 10% of all men will be given the diagnosis "prostate cancer" during their lifetime. Most of the current radio-diagnostic vehicles involve both expensive and localized production with cyclotrons as well as the use of bulky chelators for the radiometal. We report the use of a new multifunctional cyclopentadiene (Cp) platform to prepare difunctional and monofunctional, PSMA-targeting rhenium and technetium-99m complexes. The Cp-complexes and the free ligands are prepared by straightforward functionalization with either one or two Lys-urea-Glu (LuG) PSMA binding motifs. Cell binding assays revealed that the difunctional rhenium complex displays a dissociation constant (KD = 2.1 nM) that is an order of magnitude lower than the monofunctional compound (KD = 24.2 nM). The 99mTc complexes can be prepared in one step and ≤15 min in high yields. These difunctional Cp-Re(i)/99mTc(i) complexes represent a new class of imaging agents with binding affinities comparable to clinically evaluated compounds. Additionally, this study demonstrates that the Cp-platform can readily be derivatized with amine-containing biomolecules. Extending this work to incorporate both targeting and therapeutic moieties could lead to theranostic systems with Re/99mTc.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m ( 99m Tc) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent α4β2-nAChR agonist, we prepared A85380 derivatives labeled with 99m Tc using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a 99m Tc analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at α4β2-nAChR in both the docking simulation (-19.3 kcal/mol) and binding assay (Ki = 0.4 ± 0.04 nM). Further, 99m Tc-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that 99m Tc-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Bio-based synthesis of Nano-Ceria (NC) was performed in Linum usitatissimum L. (Lu) seeds extract as capping agent. Obtained gel was calcined at 400, 500, and 600 °C to investigate the effect of temperature on the size and morphology of the particles. All samples had spherical morphology which their crystallite size was decreased in higher temperature. Products were characterized by TGA/DTA, UV-vis, FESEM, FTIR and XRD. The band gap of the prepared samples was calculated through Tauc plot in the range of 3.2-3.4 eV. The results of MTT assay confirmed that NC has been shown no significant toxicity on A549 cell line. 2',7'-dichlorofluorescin diacetate (DCFDA) was used to determine antioxidant properties of NC on A549 cell and the results showed that all concentrations of NC could reduce reactive oxygen species (ROS). NC was labeled with technetium ( 99m Tc) for in vivo bio-distribution study in Wistar rat. Radiolabeled NC was stable in different environments of PBS buffer and human serum with radiochemical purity of more than 95% according to the instant thin layer chromatography (ITLC) method. DLS analysis showed radiolabeled particles had small size and pleasant colloidal stability. Bio-distribution of radiolabeled NC illustrated the highest accumulation in kidneys (1 h: 5.94 ± 0.77%ID/g, 4 h: 10.95 ± 5.99%ID/g, 24 h 7.94 ± 0.36%ID/g). Moreover, low uptake of 99m Tc-NC in stomach confirmed the in vivo stability of 99m Tc-NC. Accordingly, NC could be a worthy candidate for biological purposes and in vivo studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Graphene is one of the crystalline forms of carbon, along with diamond, graphite, carbon nanotubes, and fullerenes, and is considered as a revolutionary and innovating product. The use of a graphene-based nanolabels is one of the latest and most prominent application of graphene, especially in the field of diagnosis and, recently, in loco radiotherapy when coupled with radioisotopes. However, its biological behavior and mutagenicity in different cell or animal models, as well as the in vivo functional activities, are still unrevealed. In this study we have developed by a green route of synthesizing graphene quantum dots (GQDs) and characterized them. We have also developed a methodology for direct radiolabeling of GQDs with radioisotopes.Finally; we have evaluated in vivo biological behavior of GQDs using two different mice models and tested in vitro mutagenicity of GQDs. The results have shown that GQDs were formed with a size range of 160-280 nm, which was confirmed by DRX and Raman spectroscopy analysis, corroborating that the green synthesis is an alternative, environmentally friendly way to produce graphene. The radiolabeling test has shown that stable radiolabeled GQDs can be produced with a high yield (>90%). The in vivo test has demonstrated a ubiquitous behavior when administered to healthy animals, with a high uptake by liver (>26%) and small intestine (>25%). Otherwise, in an inflammation/VEGF hyperexpression animal model (endometriosis), a very peculiar behavior of GQDs was observed, with a high uptake by kidneys (over 85%). The mutagenicity test has demonstrated A:T to G:C substitutions suggesting that GQDs exhibits mutagenic activity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Immunotherapy with checkpoint inhibitor programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies demonstrates improvements in treatment of advanced non-small cell lung cancer. Treatment stratification depends on immunohistochemical PD-L1 measurement of biopsy material, an invasive method that does not account for spatiotemporal heterogeneity. Using a single-domain antibody, NM-01, against PD-L1, radiolabeled site-specifically with 99m Tc for SPECT imaging, we aimed to assess the safety, radiation dosimetry, and imaging characteristics of this radiopharmaceutical and correlate tumor uptake with PD-L1 immunohistochemistry results. Methods: Sixteen patients (mean age, 61.7 y; 11 men) with non-small cell lung cancer were recruited. Primary tumor PD-L1 expression was measured by immunohistochemistry. NM-01 was radiolabeled with [ 99m Tc(OH 2 ) 3 (CO) 3 ] + complex binding to its C-terminal hexahistidine tag. Administered activity was 3.8-10.4 MBq/kg, corresponding to 100 μg or 400 μg of NM-01. Whole-body planar and thoracic SPECT/CT scans were obtained at 1 and 2 h after injection in all patients, and 5 patients underwent additional imaging at 10 min, 3 h, and 24 h for radiation dosimetry calculations. All patients were monitored for adverse events. Results: No drug-related adverse events occurred in this study. The mean effective dose was 8.84 × 10 -3 ± 9.33 × 10 -4 mSv/MBq (3.59 ± 0.74 mSv per patient). Tracer uptake was observed in the kidneys, spleen, liver, and bone marrow. SPECT primary tumor-to-blood-pool ratios (T:BP) varied from 1.24 to 2.3 (mean, 1.79) at 1 h and 1.24 to 3.53 (mean, 2.22) at 2 h ( P = 0.005). Two-hour primary T:BP ratios correlated with PD-L1 immunohistochemistry results ( r = 0.68, P = 0.014). Two-hour T:BP was lower in tumors with ≤1% PD-L1 expression (1.89 vs. 2.49, P = 0.048). Nodal and bone metastases showed tracer uptake. Heterogeneity (>20%) between primary tumor and nodal T:BP was present in 4 of 13 patients. Conclusion: This first-in-human study demonstrates that 99m Tc-labeled anti-PD-L1-single-domain antibody SPECT/CT imaging is safe and associated with acceptable dosimetry. Tumor uptake is readily visible against background tissues, particularly at 2 h when the T:BP ratio correlates with PD-L1 immunohistochemistry results., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

The human epidermal growth factor receptor 2 (HER2) represents one of the most studied tumor-associated antigens for cancer immunotherapy. The receptors for HER2 are overexpressed in various human cancers, such as breast and ovarian cancer. The relatively low expression of this antigen on normal tissues makes it a clinically useful molecular target for tumor imaging and targeted therapy. HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcomes. Thus, HER2 has become an important prognostic and predictive factor, as well as a potential molecular target. Due to the heterogeneity of breast cancer and possible discordance in HER2 status between primary tumors and distant metastases, assessment of HER2 expression by noninvasive imaging is important. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in the selection of an optimal therapy. Another tumor-specific antigen is MUC1, which is silent on normal tissues, but overexpressed in almost all human epithelial cell cancers, including >90% of human breast, ovarian, pancreatic, colorectal, lung, prostate, and gastric cancers and is a promising tumor antigen with diagnostic as well as the therapeutic potential of cancer. Radiolabeled small peptide ligands are attractive as probes for molecular imaging, as they reach and bind the target receptor efficiently and clear from blood and non-target organs faster than bulky antibodies. In this study, HER2 and MUC1-based peptides were synthesized and preclinically evaluated in an effort to develop peptide-based SPECT radiopharmaceuticals derived from tumor-associated antigens for the detection of breast cancer. Our findings demonstrate that the tumor antigen peptides radiolabeled efficiently with 99m Tc and showed high metabolic stability in human plasma in vitro. The data from breast tumor cell binding confirmed the high affinity (in low nanomolar range) towards respective breast cancer cell lines. In healthy mice, 99m Tc-labeled peptides displayed favorable pharmacokinetics, with high excretion by the renal system. In tumor xenografts nude mice models, good uptake by the SKBR3, MCF7, and T47D tumors were found, with good tumor-to-blood and tumor to muscle ratios. Additionally, tumor lesions can be seen in γ-camera imaging. Our data suggest that based on its ability to detect HER2- and MUC1-positive breast cancer cells in vivo, 99m Tc-HER2 and 99m Tc-MUC1-targeted peptides may be promising tumor imaging probes and warrant further investigation.

Purpose: Pancreatic Polypeptide-secreting tumor of the distal pancreas (PPoma) is a rare, difficult and indolent type of cancer with a survival rate of 5-year in only 10% of all cases. The PPoma is classified as a neuroendocrine tumor (NET) not functioning that overexpresses SSTR 2 (somatostatin receptor subtype 2). Thus, in order to improve the diagnosis of this type of tumor, we developed nanoparticulate drug carriers based on poly-lactic acid (PLA) polymer loaded with octreotide and radiolabeled with Technetium-99 m ( 99m Tc)., Methods: PLA/PVA octreotide nanoparticles were developed by double-emulsion technique. These nanoparticles were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and radiolabeled with 99mTc by the direct via forming 99m Tc-PLA/PVA octreotide nanoparticles. The safety of these nanosystems was evaluated by the MTT cell toxicity assay and their in vivo biodistribution was evaluated in xenografted inducted animals., Results: The results showed that a 189 nm sized nanoparticle were formed with a PDI of 0,097, corroborating the monodispersive behavior. These nanoparticles were successfully radiolabeled with 99mTc showing uptake by the inducted tumor. The MTT assay corroborated the safety of the nanosystem for the cells., Conclusion: The results support the use of this nanosystem ( 99m Tc-PLA/PVA octreotide nanoparticles) as imaging agent for PPoma. Graphical Abstract Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma) Radiolabeled Nanoparticles for Imaging.

Purpose: Noninvasive imaging of treatment-induced necrosis is important to distinguish early responders from patients resistant to the treatment plan, enabling the tailored-made therapeutic intervention. The purpose of this study was to explore the feasibility of [ 99m Tc]EDDA-HYNIC-2C-rhein for early assessment of tumor response to treatment., Procedures: In vitro necrosis avidity of [ 99m Tc]EDDA-HYNIC-2C-rhein was evaluated in human lung cancer A549 cells treated with hyperthermia. Single photon emission-computed tomography/X-ray-computed tomography (SPECT/CT) imaging was performed in rats bearing subcutaneous W256 tumor treated with combretastatin A-4 disodium phosphate (CA4P) and rats bearing orthotopic liver W256 tumor treated with a single microwave ablation. All rats were euthanized immediately after the imaging session for biodistribution and histology studies. The mechanism of necrosis avidity for the tracer was further explored by in vivo blocking experiment and in vitro histochemistry and fluorescence staining., Results: The uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in necrotic cells was significantly higher than that in viable cells (p < 0.05). SPECT/CT imaging showed that an obvious "hot spot" was observed in the CA4P-treated tumor while not in the control tumor at 5 h after tracer injection. Ex vivo γ-counting revealed that the uptake of [ 99m Tc]EDDA-HYNIC-2C-rhein in tumor was increased 3.5-fold in rats treated with CA4P compared with rats treated with vehicle. Autoradiography and corresponding H&E staining suggested that the higher overall radiotracer uptake in the treated tumors was attributed to the increased necrosis. Blocking with unlabeled HYNIC-2C-rhein demonstrated the specific binding of the radiotracer to necrotic tissues. The perfect match of autoradiograph and histochemistry staining and PI fluorescence staining revealed that necrosis avidity of the tracer may be attributable to intercalation with exposed DNA in necrotic tissues., Conclusion: [ 99m Tc]EDDA-HYNIC-2C-rhein can image necrosis induced by anticancer therapy and holds potential for early assessment of treatment response.

The present study describes modification of asparagine-glycine-arginine (NGR) peptide at N-terminally and C-terminally by introduction of a tridentate chelating scaffold via click chemistry reaction. The N-terminal and C-terminal modified peptides were radiometalated with [ 99m Tc(CO) 3 ] + precursor. The influence of these moieties at the two termini on the targeting properties of NGR peptide was determined by in vitro cell uptake studies and in vivo biodistribution studies. The two radiolabeled constructs did not exhibit any significant variation in uptake in murine melanoma B16F10 cells during in vitro studies. In vivo studies revealed nearly similar tumor uptake of N-terminally modified peptide construct 5 and C-terminally construct 6 at 2 h p.i. (1.9 ± 0.1 vs 2.4 ± 0.2% ID/g, respectively). The tumor-to-blood (T/B) and tumor-to-liver (T/L) ratios of the two radiometalated peptides were also quite similar. The two constructs cleared from all the major organs (heart, lungs, spleen, stomach, and blood) at 4 h p.i. (<1% ID/g). Blocking studies carried out by coinjection of cCNGRC peptide led to approximately 50% reduction in the tumor uptake at 2 h p.i. This work thus illustrates the possibility of convenient modification/radiometalation of NGR peptide at either N- or C-terminus without hampering tumor targeting and pharmacokinetics., (© 2019 European Peptide Society and John Wiley & Sons, Ltd.)

Radionuclide molecular imaging of HER2 expression in disseminated cancer enables stratification of patients for HER2-targeted therapies. DARPin G3, a small (14 kDa) engineered scaffold protein, is a promising probe for imaging of HER2. We hypothesized that position (C- or N-terminus) and composition (hexahistidine or (HE) 3 ) of histidine-containing tags would influence the biodistribution of [ 99m Tc]Tc(CO) 3 -labeled DARPin G3. To test the hypothesis, G3 variants containing tags at N-terminus (H 6 -G3 and (HE) 3 -G3) or at C-terminus (G3-H 6 and G3-(HE) 3 ) were labeled with [ 99m Tc]Tc(CO) 3 . Labeling yield, label stability, specificity and affinity of the binding to HER2, biodistribution and tumor targeting properties of these variants were compared side-by-side. There was no substantial influence of position and composition of the tags on binding of [ 99m Tc]Tc(CO) 3 -labeled variants to HER2. The specificity of HER2 targeting in vivo was confirmed. The tumor uptake in BALB/c nu/nu mice bearing SKOV3 xenografts was similar for all variants. On the opposite, there was a strong influence of the tags on uptake in normal tissues. The tumor-to-liver ratio for [ 99m Tc]Tc(CO) 3 -(HE) 3 -G3 was three-fold higher compared to the hexahistidine-tag containing variants. Overall, [ 99m Tc]Tc(CO) 3 -(HE) 3 -G3 variant provided the highest tumor-to-lung, tumor-to-liver, tumor-to-bone and tumor-to-muscle ratios, which should improve sensitivity of HER2 imaging in these common metastatic sites.

99 Mo is an essential medical isotope that comprises of at least 70% of radioactive procedures globally. Currently an essential component of 99 Mo manufacturing is the uranium target from which 99 Mo is produced by fission. As the world moves towards low enriched uranium (LEU) targets due to non-proliferation concerns it is becoming of interest to find methods to increase the efficiency of the LEU targets in order to reduce the ever increasing nuclear waste levels of which a long term solution for disposal or treatment has yet to be satisfactorily found. Advantages and disadvantages of various target designs are investigated and discussed along current disposal and reprocessing methods. The idea of a reusable target is introduced as a way forward in reducing the nuclear waste burden for future generations., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Roxithromycin is a second-generation macrolide antibiotic derived from erythromycin. In the current study, roxithromycin (ROX) was successfully labeled with technetium-99m for early diagnosis of bacterial infection and discrimination between septic and aseptic inflammation. The highest radiochemical purity of ≥95% was achieved by investigating different labeling parameters such as pH, ligand/reducing agent concentration, temperature, and amount of stabilizing agent. For this purpose, 0.3-0.5 mg ligand, 2-6 μg SnCl 2 ·2H 2 O as a reducing agent at basic pH (8-10 pH) and 2 mg mannitol used as a stabilizing agent, in the end, 370 MBq 99m Tc added into the reaction vials and incubated for a wide range of temperature (-4 to 65°C). The percent radiochemical purity of 99m Tc-roxithromycin was assessed with the help of the radio-thin-layer chromatography technique. The characterization studies were carried out using electrophoresis and Radio-HPLC techniques as well as saline stability and serum stability studies were also performed. Furthermore, biodistribution study was also performed in an inflamed animal model to discriminate between septic (heat-killed Staphylococcus aureus) and aseptic (turpentine oil) inflammatory lesions. The results were elaborated that 99m Tc-roxithromycin ( 99m Tc-ROX) was clearly bounded at the septic inflammation site (T/NT ratio of 7.08 ± 1.14) at 30 min postadministration, and maximum accumulation was seen in heart, lungs, liver, stomach, kidneys, and intestine. The results were suggested that 99m Tc-ROX might be used to discriminate between septic and aseptic inflammatory lesions at an early stage., (© 2018 John Wiley & Sons A/S.)

Background: The evolution of nanoparticles has gained prominence as platforms for developing diagnostic and/or therapeutic radiotracers. This study aims to develop a novel technique for fabricating a tumor diagnostic probe based on iron oxide nanoparticles excluding the utilization of chelating ligands., Methods: Tc-99 m radionuclide was loaded into magnetic iron oxide nanoparticles platform (MIONPs) by sonication. 99m Tc-encapsulated MIONPs were fully characterized concerning particles size, charge, radiochemical purity, encapsulation efficiency, in-vitro stability and cytotoxicity. These merits were biologically evaluated in normal and solid tumor bearing mice via different delivery approaches., Results: 99m Tc-encapsulated MIONPs probe was synthesized with average particle size 24.08 ± 7.9 nm, hydrodynamic size 52 nm, zeta potential -28 mV, radiolabeling yield 96 ± 0.83%, high in-vitro physiological stability, and appropriate cytotoxicity behavior. The in-vivo evaluation in solid tumor bearing mice revealed that the maximum tumor radioactivity accumulation (25.39 ± 0.57, 36.40 ± 0.59 and 72.61 ± 0.82%ID/g) was accomplished at 60, 60 and 30 min p.i. for intravenous, intravenous with physical magnet targeting and intratumoral delivery, respectively. The optimum T/NT ratios of 57.70, 65.00 and 87.48 were demonstrated at 60 min post I.V., I.V. with physical magnet targeting and I.T. delivery, respectively. These chemical and biological characteristics of our prepared nano-probe demonstrate highly advanced merits over the previously reported chelator mediated radiolabeled nano-formulations which reported maximum tumor uptakes in the scope of 3.65 ± 0.19 to 16.21 ± 2.56%ID/g., Conclusion: Stabilized encapsulation of 99m Tc radionuclide into MIONPs elucidates a novel strategy for developing an advanced nano-sized radiopharmaceutical for tumor diagnosis. Graphical abstract 99m Tc-encapsulated MIONPs nanosized-radiopharmaceutical as molecular imaging probe for tumor diagnosis.

Use of both patent blue and a radioisotope to locate, and reduce the risk of sentinel lymph node (SLN) detection failure in breast cancer is recommended, but drawbacks commonly lead to using only a radioisotope. An alternative method would therefore be valuable. This randomized, controlled study in 99 patients compared SLN detection using 99m technetium (Tc) alone versus Tc combined with indocyanine green (ICG). The primary endpoint was the SLN identification rate. The primary outcome measure was the number of patients with <2 SLN detected. One SLN was detected in 44.0% of patients in the dual detection group and 40.8% in the 99m Tc alone group (RR = 1.08 (95% CI 0.68; 1.72), p = 0.84). A mean (±SD) of 2.14 ± 1.23 SLN were identified in the dual detection group vs. 1.77 ± 0.85 using Tc alone (p = 0.09). Eight-five (78.7%) SLN were both ICG+ and TC+, 15 (13.9%) ICG+ and Tc-, and 7 (6.5%) ICG- and Tc+. SLN detected were ICG-positive in 92.6% of patients and 99m Tc-positive in 85.2% with. No adverse event related to ICG injection was recorded. Dual detection of SLN using ICG and radioisotope is reliable and sensitive but was not superior to isotope alone in successfully locating SLN in our pilot randomized trial.

Purpose: Technetium-99m ( 99m Tc) is the radioisotope most widely used in diagnostic nuclear medicine. It is readily available from 99 Mo/ 99m Tc generators as the β - decay product of the 99 Mo (T &frac12;  = 66 h) parent nuclide. This latter is obtained as a fission product in nuclear reactors by neutron-induced reactions on highly enriched uranium. Alternative production routes, such as direct reactions using proton beams on specific target materials [ 100 Mo(p,2n) 99m Tc], have the potential to be both reliable and relatively cost-effective. However, results showed that the 99m Tc extracted from proton-bombarded 100 Mo-enriched targets contains small quantities of several Tc radioisotopes ( 93m Tc, 93 Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc, and 97m Tc). The aim of this work was to estimate the dose increase (DI) due to the contribution of Tc radioisotopes generated as impurities, after the intravenous injection of four radiopharmaceuticals prepared with cyclotron-produced 99m Tc (CP- 99m Tc) using 99.05% 100 Mo-enriched metallic targets., Methods: Four 99m Tc radiopharmaceuticals (pertechnetate, sestamibi (MIBI), hexamethylpropylene-amine oxime (HMPAO) and disodium etidronate (HEDP)) were considered in this study. The biokinetic models reported by the International Commission on Radiological Protection (ICRP) for each radiopharmaceutical were used to define the main source organs and to calculate the number of disintegrations per MBq that occurred in each source organ (N source ) for each Tc radioisotope present in the CP- 99m Tc solution. Then, target organ equivalent doses and effective dose were calculated for each Tc radioisotope with the OLINDA/EXM software versions 1.1 and 2.0, using the calculated N source values and the adult male phantom as program inputs. Total effective dose produced by all Tc isotopes impurities present in the CP- 99m Tc solution was calculated using the fraction of total activity corresponding to each radioisotope and compared with the effective dose delivered by the generator-produced 99m Tc., Results: In all cases, the total effective DI of CP- 99m Tc radiopharmaceuticals calculated with either versions of the OLINDA software was less than 10% from 6 up to 12 h after EOB. 94m Tc and 93m Tc are the Tc radioisotopes with the highest concentration in the CP- 99m Tc solution at EOB. However, their contribution to DI 6 h after EOB is minimal, due to their short half-lives. The radioisotopes with the largest contribution to the effective DI are 96 Tc, followed by 95 Tc and 94 Tc. This is due to the types of their emissions and relatively long half-lives, although their concentration in the CP- 99m Tc solution is five times lower than that of 94m Tc and 93m Tc at the EOB., Conclusions: The increase in the radiation dose caused by other Tc radioisotopes contained in CP- 99m Tc produced as described here is quite low. Even though the concentrations of the 94 Tc and 95 Tc radioisotopes in the CP- 99m Tc solution exceed the limits established by the European Pharmacopoeia, CP- 99m Tc radiopharmaceuticals could be used in routine nuclear medicine diagnostic studies if administered from 6 to 12 h after the EOB, thus maintaining the effective DI within the 10% limit., (© 2019 American Association of Physicists in Medicine.)

Past and prospective shortages of medical radioisotopes have driven recent developments in the direct production of 99m Tc via the 100 Mo(p,2n) 99m Tc reaction. The cyclotron-based production method has been shown to successfully produce 99m Tc, however trace impurities present in the enriched molybdenum target can also lead to the unintended creation of other radioisotopes which constitute waste. The isotopic composition of the waste has to be investigated in order to determine how it can be handled, transported and safely stored. In this article, we report which waste radioisotopes are created alongside 99m Tc during target irradiation. Results are based on the gamma spectroscopy of waste produced. Significant complexities in the emission spectra made automated identification of radioisotopes inaccurate; complexities were resolved using a manual radioisotope identification procedure. The impact of target composition, integrated beam current and duration of target irradiation on the waste produced was studied. Results indicate that an average of 0.059  ±  0.003 GBq of waste is generated per 1 GBq of 99m Tc produced. Two-thirds of the total waste activity produced was attributed to 99 Mo (T 1/2   =  66 h) alone, while a total of fifty radioisotopes were found in the waste. Long-lived isotopes (T 1/2   >  2 months) constituted only 1% of the total waste activity at end of beam (EOB). In conclusion, it was determined that the waste generated during cyclotron-based 99m Tc production was acceptably low for routine clinical production.

Iron nanoparticles are a promising new technology to treat contaminated groundwater, particularly as they can be engineered to optimise their transport properties. Technetium is a common contaminant at nuclear sites and can be reductively scavenged from groundwater by iron(II). Here we investigated the potential for a range of optimised iron nanoparticles to remove technetium from contaminated groundwater, and groundwater/sediment systems. Nano zero-valent iron and Carbo-iron stimulated the development of anoxic conditions while generating Fe(II) which reduced soluble Tc(VII) to sparingly soluble Tc(IV). Similar results were observed for Fe(II)-bearing biomagnetite, albeit at a slower rate. Tc(VII) remained in solution in the presence of the Fe(III) mineral nano-goethite, until acetate was added to stimulate microbial Fe(III)-reduction after which Tc(VII) concentrations decreased concomitant with Fe(II) ingrowth. The addition of iron nanoparticles to sediment microcosms caused an increase in the relative abundance of Firmicutes, consistent with fermentative/anoxic metabolisms. Residual bacteria from the synthesis of the biomagnetite nanoparticles were out-competed by the sediment microbial community. Overall the results showed that iron nanoparticles were highly effective in removing Tc(VII) from groundwater in sediment systems, and generated sustained anoxic conditions via the stimulation of beneficial microbial processes including Fe(III)-reduction and sulfate reduction., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Niosomes are nonionic surfactant-based vesicles that exhibit certain unique features which make them favorable nanocarriers for sustained drug delivery in cancer therapy. Biodistribution studies are critical in assessing if a nanocarrier system has preferential accumulation in a tumor by enhanced permeability and retention effect. Radiolabeling of nanocarriers with radioisotopes such as Technetium-99m ( 99m Tc) will allow for the tracking of the nanocarrier noninvasively via nuclear imaging. The purpose of this study was to formulate, characterize, and optimize 99m Tc-labeled niosomes., Methods: Niosomes were prepared from a mixture of sorbitan monostearate 60, cholesterol, and synthesized D-α-tocopherol polyethylene glycol 1000 succinate-diethylenetriaminepentaacetic acid (synthesis confirmed by 1 H and 13 C nuclear magnetic resonance spectroscopy). Niosomes were radiolabeled by surface chelation with reduced 99m Tc. Parameters affecting the radiolabeling efficiency such as concentration of stannous chloride (SnCl 2 ·H 2 O), pH, and incubation time were evaluated. In vitro stability of radiolabeled niosomes was studied in 0.9% saline and human serum at 37°C for up to 8 hours., Results: Niosomes had an average particle size of 110.2±0.7 nm, polydispersity index of 0.229±0.008, and zeta potential of -64.8±1.2 mV. Experimental data revealed that 30 µg/mL of SnCl 2 ·H 2 O was the optimal concentration of reducing agent required for the radiolabeling process. The pH and incubation time required to obtain high radiolabeling efficiency was pH 5 and 15 minutes, respectively. 99m Tc-labeled niosomes exhibited high radiolabeling efficiency (>90%) and showed good in vitro stability for up to 8 hours., Conclusion: To our knowledge, this is the first study published on the surface chelation of niosomes with 99m Tc. The formulated 99m Tc-labeled niosomes possessed high radiolabeling efficacy, good stability in vitro, and show good promise for potential use in nuclear imaging in the future., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

In this study, we developed, characterized, and tested in vivo polymeric nanoparticle of ethambutol labeled with 99mTc as nanoradiopharmaceutical for early diagnosis of tuberculosis by single-photon emission computed tomography, also as a therapeutic choice. Nanoparticles were developed by double emulsification. All characterization tests were performed, as scanning electron microscopy and dynamic light scattering. The labeling process with 99mTc was performed using the direct labeling process. In vitro and in vivo assays were performed with animals and cells. The results showed that a spherical ethambutol nanoparticle with a size range of 280-300 nm was obtained. The stability test showed that the nanoparticles were well labeled with 99mTc (> 99.1%) and keep labeled over 24 h. The biodistribution assay showed that almost 18% of the nanoparticles were uptake by the lung in infected mice (male C57Bl/6) with Mycobacterium bovis BCG (4 × 10 5  CFU/cavity), corroborating its use as a nanodrug for tuberculosis imaging. The results for the cell assay corroborate its therapeutical effect. We developed and efficiently tested a new nanodrug that can be used for both imaging and therapy of tuberculosis, acting as a novel nanotheranostic.

The somatostatin receptor subtype 2 (SSTR2) is often highly expressed on neuroendocrine tumors (NETs), making it a popular in vivo target for diagnostic and therapeutic approaches aimed toward management of NETs. In this work, an antagonist peptide (sst 2 -ANT) with high affinity for SSTR2 was modified at the N-terminus with a novel [N,S,O] bifunctional chelator (2) designed for tridentate chelation of rhenium(I) and technetium(I) tricarbonyl cores, [Re(CO) 3 ] + and [ 99m Tc][Tc(CO) 3 ] + . The chelator-peptide conjugation was performed via a Cu(I)-assisted click reaction of the alkyne-bearing chelator (2) with an azide-functionalized sst 2 -ANT peptide (3), to yield NSO-sst 2 -ANT (4). Two synthetic methods were used to prepare Re-4 at the macroscopic scale, which differed based on the relative timing of the click conjugation to the [Re(CO) 3 ] + complexation by 2. The resulting products demonstrated the expected molecular mass and nanomolar in vitro SSTR2 affinity (IC 50 values under 30 nM, AR42J cells, [ 125 I]iodo-Tyr 11 -somatostatin-14 radioligand standard). However, a difference in their HPLC retention times suggested a difference in metal coordination modes, which was attributed to a competing N-triazole donor ligand formed during click conjugation. Surprisingly, the radiotracer scale reaction of [ 99m Tc][Tc(OH 2 ) 3 (CO) 3 ] + ( 99m Tc; t ½  = 6 h, 141 keV γ) with 4 formed a third product, distinct from the Re analogues, making this one of the unusual cases in which Re and Tc chemistries are not well matched. Nevertheless, the [ 99m Tc]Tc-4 product demonstrated excellent in vitro stability to challenges by cysteine and histidine (≥98% intact through 24 h), along with 75% stability in mouse serum through 4 h. In vivo biodistribution and microSPECT/CT imaging studies performed in AR42J tumor-bearing mice revealed improved clearance of this radiotracer in comparison to a similar [ 99m Tc][Tc(CO) 3 ]-labeled sst 2 -ANT derivative previously studied. Yet despite having adequate tumor uptake at 1 h (4.9% ID/g), tumor uptake was not blocked by co-administration of a receptor-saturating dose of SS-14. Aimed toward realignment of the Re and Tc product structures, future efforts should include distancing the alkyne group from the intended donor atoms of the chelator, to reduce the coordination options available to the [M(CO) 3 ] + core (M = Re, 99m Tc) by disfavoring involvement of the N-triazole., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In the field of angiogenesis, small cyclic pentapeptides containing the RGD motif are playing a relevant role for their high affinity and specificity for integrin receptors and for the possibility to act at both therapeutic and diagnostic level by inhibiting pathological angiogenesis and by serving as shuttles to deliver imaging-probe including SPECT/PET radionuclides to specific tissues. In the last decade, several new protocols were reported in literature for the direct synthesis of cyclic RDG either in solution or by SPPS. Here, we have elaborated and tested some alternative approaches using different resins and different protective groups. The introduction of the dithiocarbamate function, useful to complex radio-metals suitable for nuclear medicine applications, has also been considered and achieved., (© 2019 European Peptide Society and John Wiley & Sons, Ltd.)

Objectives: This study was designed to investigate the efficacy of 99m technetium-three polyethylene glycol spacers-arginine-glycine-aspartic acid ([ 99m Tc]3PRGD 2 ) in the evaluation of patients with esophageal cancer., Methods: Twenty-nine patients with a suspected esophageal lesion and for whom definite pathological diagnosis was finally obtained were recruited. Whole-body planar scanning and chest single-photon-emission computed tomography/computed tomography (SPECT/CT) were performed at 30 and 40 min, respectively, after intravenous injection of 11.1 MBq/kg of [ 99m Tc]3PRGD 2 . 2-Deoxy-2-[ 18 F] fluoro-D-glucose ([ 18 F]FDG) positron-emission tomography/computed tomography (PET/CT) was performed in 1 week. The tumor-to-background ratio (T/B) and the maximum standard uptake value (SUVmax) were calculated for semi-quantitative and quantitative analyses. Integrin α v β 3 was analyzed through immunohistochemistry., Results: The T/B, SUVmax and expression of integrin α v β 3 in malignant lesions were higher than those in benign lesions (t = 3.691, P = 0.001; t = 8.271, P = 0.000; t = 3.632, P = 0.001, respectively). There was a significant correlation between T/B and SUVmax in esophageal lesions (r = 0.660, P = 0.000). The expression of integrin α v β 3 was correlated with [ 99m Tc]3PRGD 2 uptake (r = 0.782, P = 0.000). In visual analysis, the sensitivity and accuracy of the whole-body planar RGD scan were lower than those of the chest SPECT/CT RGD scan and the [ 18 F]FDG PET/CT scan (x 2  = 6.769, P = 0.022). The sensitivity, specificity and accuracy of the chest SPECT/CT RGD scan were similar to those of the [ 18 F] FDG PET/CT scan. In semi-quantitative analysis, the sensitivity, specificity and accuracy of chest SPECT/CT RGD from the receiver operating characteristic (ROC) analysis were 87%, 100% and 94%, respectively [cutoff = 3.1 of T/B, area under the curve (AUC) = 0.957]. Thirteen patients (30 lymph nodes) and 16 patients (105 lymph nodes) were suspected to have lymph node metastases based on the RGD and FDG scans, respectively., Conclusion: This prospective study demonstrated that [ 99m Tc]3PRGD 2 imaging is valuable for the diagnosis and staging of esophageal cancer. It may be less sensitive than [ 18 F]FDG imaging for detecting metastatic lesions in small lymph nodes. The T/B value was correlated with the expression of integrin α v β 3 . NIH CLINICALTRIALS.GOV: NCT 02744729.

Liposomes are lipid vesicles widely used as nanocarriers in targeted drug delivery systems for therapeutic and/or diagnostic purposes. A strategy to prolong the blood circulation time of the liposomes includes the addition of a hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the vesicle. Several studies claim that liposome PEGylation by a single chain length or a combination of PEG with different chain lengths may alter the liposomes' pharmacokinetic properties. Therefore, the purpose of this study was to evaluate the influence of PEG on the biodistribution of pH-sensitive liposomes in a tumor-bearing animal model. Three liposomal formulations (PEGylated or not) were prepared and validated to have a similar mean diameter, monodisperse distribution, and neutral zeta potential. The pharmacokinetic properties of each liposome were evaluated in healthy animals, while the biodistribution and scintigraphic images were evaluated in tumor-bearing mice. High tumor-to-muscle ratios were not statistically different between the PEGylated and non-PEGylated liposomes. While PEGylation is a well-established strategy for increasing the blood circulation of nanostructures, in our study, the use of polymer coating did not result in a better in vivo profile. Further studies must be carried out to confirm the feasibility of the non-PEGylated pH-sensitive liposomes for tumor treatment.

Background: Electronic cigarettes (ECIGs) are widely used, but their health effects are not well known. ECIG exposure is difficult to quantify, and a direct measurement of deposition would be beneficial to in vivo and in vitro toxicity studies. The aim of this study was to demonstrate effective radiolabeling of an ECIG., Methods: A technetium-99m-labeled carbon ultrafine (TCU) aerosol was generated and introduced to a fourth-generation ECIG before nucleation and aerosol formation. The aerosolized e-liquid was a commercially available strawberry flavor containing 1.2% nicotine in a 55% propylene glycol and 45% vegetable glycerine base. An ECIG power setting of 100 W was selected. Mass and radioactivity were measured on each stage within a Sierra Cascade Impactor at 14 L/min to verify the labeling technique using the calculated aerodynamic diameters. A strong positive correlation (R 2  > 0.95) between the percent activity and percent mass deposition on each stage provides a reliable validation of colocation., Results: Unlabeled ECIG aerosol from the chosen e-liquid produced a mass median aerodynamic diameter (MMAD) of 0.85 μm. An ECIG labeled with TCU produced an aerosol with an activity median aerodynamic diameter of 0.84 μm and an MMAD of 0.84 μm. The relative mass versus radioactivity on each plate was highly correlated (average R 2  = 0.973, p < 0.001)., Conclusion: A TCU radiolabel was generated and shown to associate with the mass of an aerosol produced by a typical commercially available ECIG. Thus, the radioactivity of the deposited aerosol may be used to determine ECIG aerosol deposition for the future in vivo and in vitro dosimetry studies of the third- and fourth-generation ECIGs.

The development of functional imaging is a promising strategy for diagnosis and treatment of infectious and cancerous diseases. In this study, epirubicin was developed as a [ 99m Tc]-labeled radiopharmaceutical for the imaging of multi-drug-resistant Staphylococcus aureus infections. The labeling was carried out using sodium pertechnetate (Na 99m TcO 4 ; ~370 MBq). The other parameters such as amount of ligand, reducing agent (SnCl 2 .2H 2 O), and pH were optimized. The highest labeling yield ≥96.98% was achieved when 0.3 mg epirubicin, 13 μg SnCl 2 .2H 2 O, and ~370 MBq Na 99m TcO 4 were incubated at pH 7 for 15 min in the presence of ascorbic acid at room temperature. Radiochemical purity, stability, charge, and glomerular filtration rate were studied to evaluate the biological compatibility for in vivo administration. Biodistribution investigations showed radiotracer uptake (13.89 ± 1.56% ID/gm organ) by liver and 7.79 ± 0.38% ID/gm organ by kidneys at 30 min post-injection which promisingly wash out at 24 hr post-injection. Scintigraphy study showed selective uptake in S. aureus-infected tissues in contrast to turpentine oil-induced inflamed tissues. Target-to-non-target ratio (6.7 ± 0.05) was calculated at 1 hr post-injection using SPECT gamma camera. The results of this study reveal that the [ 99m Tc]-epirubicin can be a choice of imaging and monitoring the treatment process of multi-drug resistant S. aureus bacterial infections., (© 2018 John Wiley & Sons A/S.)

Purpose: Selective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, 99m Technetium-labeled macroaggregated albumin ( 99m Tc-MAA). We report a new composite consisting of 99m Tc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT., Methods: Carbon nanoparticles with an encapsulated core of 99m Tc were coated with the polycation protamine sulfate to provide electrostatic attachment to anionic polystyrene sulfonate microspheres of different sizes (30, 12, and 8 µm). The in vivo stability of these composites was determined via intravenous injection and entrapment in the capillary network of normal rabbit lungs for up to 3 hours. Furthermore, we evaluated their biodistribution in normal rabbit livers, and livers implanted with VX2 tumors, following intrahepatic artery instillation., Results: We report distribution tests for three different sizes of radiolabeled microspheres and compare the results with those obtained using 99m Tc-MAA. Lung retention of the radiolabeled microspheres ranged from 72.8% to 92.9%, with the smaller diameter microspheres showing the lowest retention. Liver retention of the microspheres was higher, with retention in normal livers ranging from 99.2% to 99.8%, and in livers with VX2 tumors from 98.2% to 99.2%. The radiolabeled microspheres clearly demonstrated preferential uptake at tumor sites due to the increased arterial perfusion produced by angiogenesis., Conclusion: We describe a novel use of radiolabeled carbon nanoparticles to generate an imageable microsphere that is stable in vivo under the shear stress conditions of arterial networks. Following intra-arterial instillation in the normal rabbit liver, they distribute in a distinct segmented pattern, with the smaller microspheres extending throughout the organ in finer detail, while still being well retained within the liver. Furthermore, in livers hosting an implanted VX2 tumor, they reveal the increased arterial perfusion of tumor tissue resulting from angiogenesis. These novel composites may have potential as a more representative mimic of the vascular distribution of therapeutic microspheres in patients undergoing SIRT., Competing Interests: Disclosure The radiolabeling method employed in this study is the subject of US patent 9,381,262, granted July 5, 2016. MRT, JGW, SAB, MJT, and SKJ are employed by Sirtex Medical Limited. The authors report no other conflicts of interest in this work.

Despite the widespread use of nanotechnology in radio-imaging applications, lipoprotein based delivery systems have received only limited attention so far. These studies involve the synthesis of a novel hydrophobic radio-imaging tracer consisting of a hydrazinonicotinic acid (HYNIC)-N-dodecylamide and 99mTc conjugate that can be encapsulated into rHDL nanoparticles (NPs). These rHDL NPs can selectively target the Scavenger Receptor type B1 (SR-B1) that is overexpressed on most cancer cells due to excess demand for cholesterol for membrane biogenesis and thus can target tumors in vivo. We provide details of the tracer synthesis, characterization of the rHDL/tracer complex, in vitro uptake, stability studies and in vivo application of this new radio-imaging approach.

Background: Pancreatic Neuroendocrine Tumors (PNETs) are rare neoplasms, sporadic or familial, even being part of a syndrome. Their diagnosis is based on symptoms, hormonal disorders or may be fortuitous. The role of Nuclear Medicine is important, mainly because of the possibility of a theranostic strategy. This approach is allowed by the availability of biochemical agents, which may be labeled with radionuclides suitable for diagnostic or therapeutic purposes, showing almost identical pharmacokinetics. The major role for radiopharmaceuticals is connected with radiolabeled Somatostatin Analogues (SSA), since somatostatin receptors are highly expressed on some of the neoplastic cell types., Discussion: Nowadays, in the category of radiolabeled SSA, although 111In-pentetreotide, firstly commercially proposed, is still used, the best choice for diagnosis is related to the so called DOTAPET radiotracers labeled with 68-Gallium (Ga), such as 68Ga-DOTATATE, 68Ga-DOTANOC, and 68Ga-DOTATOC. More recently, labeling with 64-Copper (Cu) (64Cu-DOTATATE) has also been proposed. In this review, we discuss the clinical interest of a SAA (Tektrotyd©) radiolabeled with 99mTc, a gamma emitter with better characteristics, with respect to 111Indium, radiolabeling Octreoscan ©. By comparing both pharmacokinetics and pharmacodynamics of Octreoscan©, Tektrotyd© and PET DOTA-peptides, on the basis of literature data and of our own experience, we tried to highlight these topics to stimulate further studies, individuating actual clinical indications for all of these radiotracers., Conclusion: In our opinion, Tektrotyd© could already find its applicative dimension in the daily practice of NETs, either pancreatic or not, at least in centers without a PET/CT or a 68Ga generator. Because of wider availability, a lower cost, and a longer decay, compared with respect to peptides labeled with 68Ga, it could be also proposed, in a theranostic context, for a dosimetry evaluation of patients undergoing Peptide Receptor Radionuclide Therapy (PRRT), and for non-oncologic indications of radiolabelled SSA. In this direction, and for a more rigorous cost/effective evaluation, more precisely individuating its clinical role, further studies are needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Leishmaniasis is a neglected disease endemic in tropical and subtropical areas, with an incidence about 1.6 million cases/year. The first-line treatment of this disease is pentavalent antimony, and the second-line are pentamidine and amphotericin B. All the treatments available cause severe side effects and often have difficulty in accessing parasites within infected cells., Study Question: This study aimed to determine if the use of nanoparticles loaded with meglumine antimoniate could reach and targeting infected organs with leishmaniasis, reducing the dosage used and promoting less adverse effects., Study Design: This study was performed comparing the meglumine nanoparticle in two experimental groups. The first one healthy mice and the second one inducted mice (leishmaniasis)., Measures and Outcomes: The nanoparticles loaded with meglumine antimoniate (nanoantimony) were prepared by double-emulsion solvent evaporation method and showed a size of about 150-200 nm. BALB/c mice infected or not with Leishmania amazonensis (cutaneous leishmaniasis model) or Leishmania infantum (visceral leishmaniasis model) was used to access the biodistribution of nanoantimony and meglumine antimoniate labeled with technetium-99m., Results: The biodistribution profiles showed a preferential targeting of the nanoparticles to the liver, spleen, and lungs. Because these are the main organs infected, the nanoparticle may be used for this purpose. The results for cutaneous leishmaniasis showed a low uptake by the lesion (infected region)., Conclusions: The results demonstrated the potential use of these nanoparticles to improve the efficacy of meglumine antimoniate in the treatment of visceral leishmaniasis, indicating their potential as an alternative therapeutic strategy for leishmaniasis infections.

Introduction: meta-[ 123/131 I]Iodobenzylguanidine (mIBG) is a clinical agent used for imaging neuroendocrine tumors, where uptake in tumor is via active transport mechanism through norepinephrine transporters (NET). Our group in past have evaluated a 99m Tc-analogue of the above tracer, based on 99m Tc-4 + 1 labeling approach, which exhibited significant affinity for NET but suffered from reduced specific uptake in comparison to reference standard no-carrier-added (n.c.a.) [ 125 I]mIBG. The present work attempts to synthesize two new 99m Tc-analogues of the radio-iodinated derivative following [ 99m Tc]Tc(CO) 3 1+ approach with an aim to improve the above specific uptake content., Methods: Two different precursors, xylylenediamine and 1,3-bis(chloromethyl)benzene, were synthetically modified to yield meta-functionalized benzylguanidine derivatives bearing iminodiacetate (IDA) and aminoethylglycine (AEG) tridentate chelating moieties, respectively. These ligands were labeled with technetium-99m via [ 99m Tc][Tc(CO) 3 (H 2 O) 3 ] + synthon to form desired radioactive complexes 9 and 10. The radiolabeling yields of the complexes obtained were >90% as confirmed by radio-HPLC. The HPLC purified complexes were used for in vitro and in vivo evaluation to understand the true biological efficacy. Structural characterization of the radiolabeled complexes was carried after synthesizing and characterizing their Re-analogues., Results: Cell uptake studies with the radiolabeled complexes in SK-N-SH neuroblastoma cell lines revealed reduced uptake in the cells (<1% of incubated radioactivity/10 6 cells) in comparison to n.c.a. [ 125 I]mIBG (~12%). However, limited specificity (~60%) was observed for the complexes as ascertained through desmethylimipramine (DMI) inhibition. Biodistribution studies in normal Wistar rats exhibited desired non-target clearance pharmacokinetics for the complexes but in vivo NET efficacy in myocardium for the neutral complex 10 could not be established., Conclusions: Tridentate [ 99m Tc]Tc(CO) 3 1+ chelation approach severely affects biological behavior of the present small bioactive molecule under study to a significant extent in comparison to monodentate ligation in 99m Tc-4 + 1 strategy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The characterization of cancerous tissue and bone metastasis can be distinguished by accurate assessment of accumulated uptake and activity from different radioisotopes. The various parameters and phenomena such as calibration factor, Compton scattering, attenuation and penetration intrinsicallyinfluence calibration equation, and the qualification of images as well., Methods: The camera calibration factor (CF) translates reconstructed count map into absolute activity map, which is determined by both planar and tomographic scans using different phantom geometries. In this study, the CF for radionuclides of Tc-99m and Sm-153 in soft tissue and bone was simulated by the Monte Carlo method, and experimental results were obtained in equivalent tissue and bone phantoms. It may be employed for the simultaneous correction of the scattering and attenuation rays interacted with the camera, leading to corrected counts. Also, the target depth (d) may be estimated by a combination of scattering and photoelectric functions, which we have published before., Results: The calibrated equations for soft tissue phantom for the radionuclides were obtained by RTc = - 10d+ 300 and RSm = -8d + 100, and the relative errors between the simulated and experimental results were 4.5% and 3.1%, respectively. The equations for bone phantom were RTc = -30d + 300 and RSm = - 10d + 100, and the relative errors were 5.4% and 5.6%. The R and d are in terms of cpm/mCi and cm. Besides, the collimators' impact was evaluated on the camera response, and the relevant equations were obtained by the Monte Carlo method. The calibrated equations as a function of various radiation angles on the center of camera's cells without using collimator indicated that both sources have the same quadratic coefficient by -2E-08 and same vertical width from the origin by 8E-05., Conclusion: The presented procedure may help determine the absorbed dose in the target and likewise optimize treatment planning., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)