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Benchtop 99 Mo/ 99m Tc and 188 W/ 188 Re generators enable economical production of molecular theranostic 99m Tc and 188 Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates 99m Tc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with 99m Tc and 188 Re for diagnostic imaging and systemic radiotherapy of prostate cancer. Methods: Two diphosphine-dipeptide bioconjugates, DP1-PSMAt and DP2-PSMAt, were formulated into kits for radiolabeling with 99m Tc and 188 Re. The resulting radiotracers were studied in vitro, in prostate cancer cells, and in vivo in mouse xenograft models, to assess similarity of uptake and biodistribution for each 99m Tc/ 188 Re pair of agents. Results: Both DP1-PSMAt and DP2-PSMAt could be efficiently radiolabeled with 99m Tc and 188 Re using kit-based methods to furnish the isostructural compounds M-DP1-PSMAt and M-DP2-PSMAt (M = [ 99m Tc]Tc, [ 188 Re]Re). All 99m Tc/ 188 Re radiotracers demonstrated specific uptake in PSMA-expressing prostate cancer cells, with negligible uptake in prostate cancer cells that did not express PSMA or in which PSMA uptake was blocked. M-DP1-PSMAt and M-DP2-PSMAt also exhibited high tumor uptake (18-30 percentage injected dose per gram at 2 h after injection), low retention in nontarget organs, fast blood clearance, and excretion predominantly via a renal pathway. Importantly, each pair of 99m Tc/ 188 Re radiotracers showed near-identical biologic behavior in these experiments. Conclusion: We have prepared and developed novel pairs of isostructural PSMA-targeting 99m Tc/ 188 Re theranostic agents. These generator-based theranostic agents have potential to provide access to the benefits of PSMA-targeted diagnostic imaging and systemic radiotherapy in health care settings that do not routinely have access to either reactor-produced 177 Lu radiopharmaceuticals or PET/CT infrastructure., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Nuclear medicine staff are constantly exposed to low doses of ionizing radiation. This study investigated the level of genotoxic effects in hospital employees exposed to routinely used 131 I and 99m Tc in comparison with a control group. The study compared the results of physical and biological monitoring in peripheral blood lymphocytes. The effects of confounding factors, such as smoking status and physical activity, were also considered. Physical dosimetry monitoring revealed differences in the individual annual effective dose as measured by finger ring dosimeter and whole-body dosimeter between the 131 I- and 99m Tc-exposed groups. The DNA damage studies revealed differences between the groups in terms of excess premature chromosome condensation (PCC) fragments and tail DNA. Physical activity and smoking status differentiated the investigated groups. When assessed by the level of physical activity, the highest mean values of tail DNA were observed for the 99m Tc group. When assessed by work-related physical effort, excess PCC fragments were significantly higher in the 131 I group than in the control group. In the investigated groups, the tail DNA values were significantly different between non-smokers and past or current smokers, but excess PCC fragments did not significantly differ by smoking status. It is important to measure exposure to low doses of ionizing radiation and assess the potential risk from this exposure. Such investigations support the need to continue epidemiological and experimental studies to improve our understanding of the mechanisms of the health effects of radionuclides and to develop predictive models of the behavior of these complex systems in response to low-dose radiation.

Background: Macroaggregated human serum albumin (MAA) properties are widely used in nuclear medicine, labelled with 99m Tc. The aim of this study is to improve the knowledge about the morphology, size, dimension and physical-chemical characteristics of MAA and their bond with 99m Tc and 68 Ga., Methods: Commercial kits of MAA (Pulmocis ® ) were used. Characterisation through experiments based on SEM, DLS and Stokes' Law were carried out. In vitro experiments for Langmuir isotherms and pH studies on radiolabelling were performed and the stability of the radiometal complex was verified through competition reactions., Results: The study settles the MAA dimension within the range 43-51 μm. The Langmuir isotherm reveals for [ 99m Tc]MAA: Bmax (46.32), h (2.36); for [ 68 Ga]MAA: Bmax (44.54), h (0.893). Dual labelling reveals that MAA does not discriminate different radioisotopes. Experiments on pH placed the optimal pH for labelling with 99m Tc at 6., Conclusion: Radiolabelling of MAA is possible with high efficiency. The nondiscriminatory MAA bonds make this drug suitable for radiolabelling with different radioisotopes or for dual labelling. This finding illustrates the need to continue investigating MAA chemical and physical characteristics to allow for secure labelling with different isotopes.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts (CAFs) in a majority of human epithelial cancers. With low expression in normal organs, FAP has become a promising molecular target for tumor theranostics. To develop a lower cost and more widely available alternative to positron emission tomography (PET), two isocyanide-containing FAP inhibitors (CN-C 5 -FAPI and CN-PEG 4 -FAPI) were synthesized and radiolabeled with 99m Tc to obtain [ 99m Tc][Tc-(CN-C 5 -FAPI) 6 ] + and [ 99m Tc][Tc-(CN-PEG 4 -FAPI) 6 ] + in high yields (>95%). They showed good stability in saline and mouse serum. The partition coefficient (log  P ) values of [ 99m Tc][Tc-(CN-C 5 -FAPI) 6 ] + and [ 99m Tc ] [Tc-(CN-PEG 4 -FAPI) 6 ] + were -0.86 ± 0.03 and -2.38 ± 0.07, respectively, indicating that they were good hydrophilic complexes. The low nanomolar IC 50 values of CN-C 5 -FAPI and CN-PEG 4 -FAPI indicated that they had specificity to FAP. In vitro cellular uptake and blocking experiments implied a FAP-targeted uptake mechanism. The nanomolar K d values from the saturation binding assay indicated that they had significantly high target affinity to FAP. The biodistribution and blocking study in BALB/c nude mice bearing U87MG tumors showed that both exhibited specific tumor uptake. [ 99m Tc][Tc-(CN-PEG 4 -FAPI) 6 ] + showed a higher tumor uptake and a higher tumor/nontarget ratio than [ 99m Tc][Tc-(CN-C 5 -FAPI) 6 ] + . The results of micro-single-photon emission computed tomography (SPECT) imaging studies of [ 99m Tc][Tc-(CN-C 5 -FAPI) 6 ] + and [ 99m Tc ] [Tc-(CN-PEG 4 -FAPI) 6 ] + were in accordance with the biodistribution results, suggesting that [ 99m Tc][Tc-(CN-PEG 4 -FAPI) 6 ] + is a promising tumor imaging agent for targeting FAP.

This paper presents results of measurements of 99m Tc activity concentration in air and nuclear medical personnel blood during ventilation-perfusion SPECT lung scans. 99m Tc activity measurements were conducted at the Nuclear Medicine Department, John Paul II Hospital, Krakow. Technicians and nurses who perform examinations were equipped with personal aspirators enabling air sampling to determine the radiation exposure at their workplaces. Measurements allowed to evaluate the concentration of 99m Tc in 14 air samples and it ranged from 7800 ± 600 to 10,000 ± 1000 Bq m -3 for air samples collected by technicians and from 390 ± 30 to 600 ± 40 Bq m -3 for air samples collected by nurses. In addition 99m Tc concentrations in blood of medical personnel were determined in 24 samples. For technicians the maximum 99m Tc blood concentration levels reached 920 ± 70 Bq L -1 and 1300 ± 100 Bq L -1 . In the case of nurses, the maximum estimated activity concentrations were about ten times lower, namely 71 ± 7 Bq L -1 and 39 ± 3 Bq L -1 . Although the intakes appear to be relatively high, the resulting annual effective doses are about 34 µSv for technicians and only 2 µSv for nurses.

Nanomedicine is a highly demanded discipline. Liposomes have seen an increased attention due to their physicochemical properties that allow them to act as nanocarriers of drugs and also of radioisotopes that can be used to diagnose and treat cancer. In order to obtain a novel permeability cancer imaging agent based on 99m Tc-labeled liposomes, we describe microwave-assisted synthesis of stearyl 6-(benzylidenehydrazinyl) nicotinamide lipid, which was included in two formulations: nanometric hydrazinonicotinic acid (HYNIC) liposome and its PEGylated coated analogue, HYNIC-PEG liposome. Radiolabeling with 99m Tc via stearyl 6-(benzylidenehydrazinyl) nicotinamide was found to be easy, reproducible, and stable, revealing high radiochemical purity (94 ± 1.7%) for both liposomal formulations. Biodistribution at 4 h and 24 h and scintigraphic images at 4 h were performed in normal and melanoma-bearing C57BL/6 mice. Biodistribution studies at 4 h showed tumor uptake of 99m Tc-HYNIC liposome and 99m Tc-HYNIC-PEG liposome (1.1 ± 0.6 and 2.5 ± 0.4, respectively) and also at 24 h p.i. (1.8 ± 0.5 and 3.0 ± 1.1, respectively). Scintigraphic images showed appreciable tumor uptake in melanoma tumor-bearing mice with both liposomal formulations. Our results show that 99m Tc stearyl 6-(benzylidenehydrazinyl) nicotinamide liposomes can be used as diagnostic noninvasive in vivo tumor-targeting agents capable of evaluating tumor permeability and development who can be used in personalized chemotherapy planning.

Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties., Objective: In this study, it has been aimed to develop a novel targeted 99m Tc radiolabeled polymeric drug delivery system for Gemcitabine (GEM)., Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with 99m Tc. SPIONs were synthesized by reduction-coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. The radiolabeling yield of SPION-PLGAGEM nanoparticles was determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA was investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro., Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles was determined as 366.6 nm by DLS, while zeta potential was found as 29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4±0.16% by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles was determined as 97.8±1.75% via TLRC. Cytotoxicity of GEM loaded SPION-PLGA was investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, while the incorporation rate was increased for both cell lines with external magnetic field application., Conclusion: 99m Tc labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and superparamagnetic characteristics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Prostate-specific membrane antigen (PSMA) is a well-established biological target that is overexpressed on the surface of prostate cancer lesions. Radionuclide-labeled small-molecule PSMA inhibitors have been shown to be promising PSMA-specific agents for the diagnosis and therapy of prostate cancer. In this study, a glutamate-urea-based PSMA-targeted ligand containing an isonitrile (CNGU) was synthesized and labeled with 99m Tc to prepare [ 99m Tc]Tc-CNGU with a high radiochemical purity (RCP). The CNGU ligand showed a high affinity toward PSMA ( K i value is 8.79 nM) in LNCaP cells. The [ 99m Tc]Tc-CNGU exhibited a good stability in vitro and hydrophilicity (log P = -1.97 ± 0.03). In biodistribution studies, BALB/c nude mice bearing LNCaP xenografts showed that the complex had a high tumor uptake with 4.86 ± 1.19% ID/g, which decreased to 1.74 ± 0.90% ID/g after a pre-injection of the selective PSMA inhibitor ZJ-43, suggesting that it was a PSMA-specific agent. Micro-SPECT imaging demonstrated that the [ 99m Tc]Tc-CNGU had a tumor uptake and that the uptake was reduced in the image after blocking with ZJ-43, further confirming its PSMA specificity. All of the results in this work indicated that [ 99m Tc]Tc-CNGU is a promising PSMA-specific tracer for the imaging of prostate cancer.

Objective: The APT EDB is an aptide specific to the extra domain B (EDB) of fibronectin with high affinity for EDB, which is expressed in malignant tumors including brain cancer (U87MG) and colorectal cancer (HT-29). Aim of this study was to evaluate the [ 99m Tc] Tc-APT EDB potential as an imaging probe for colorectal cancer., Methods: Radiochemical purity was evaluated by HPLC and radio-isotope TLC scanner. Blocking study for specific binding assay and affinity calculation (K d ) on HT-29 cell lines were also carried out. Planar imaging and bio-distribution studies were performed in HT-29 tumor-bearing mice., Results: The APT EDB was efficiently labeled with technetium-99m in high radiochemical yield (up to 97%). Cellular binding study demonstrated specific binding of the [ 99m Tc] Tc-APT EDB in cultured HT-29 cells. The K d value was found to be 40.46 ± 13.39 nM. The tumor-to-muscle ratio was ~ 1.5 in ex vivo bio-distribution study at 1 h after injection. Planar imaging study showed higher activity accumulation in EDB expressing HT-29 tumor relative to muscle (used as control) (~ 1.7) at 1 h., Conclusions: Although more studies are required to find out the full potential of this radio-ligand as an imaging probe, the present results nevertheless provide useful information about [ 99m Tc] Tc-APT EDB , which might be beneficial in design and development of new [ 99m Tc] Tc-APT EDB for efficient targeting of tumor in vivo.

Dendrimer-based targeted drug delivery, as an innovative polymeric drug-delivery system, is promising for cancer therapy. Folate receptors (FR) are overexpressed in many types of tumor cells, such as breast cell carcinomas, which allow folate-targeted delivery. Therefor polyethylene glycol (PEG) modified-PAMAM G4 dendrimers were functionalized with folic acid (FA), as targeting agent. Then, 5-FU (5-fluorouracil) and 99m Tc (technetium-99 m) as therapeutic agents were respectively loaded and conjugated to previous nano-complex (PEG-PAMAM G4-FA-5FU- 99m Tc). The value of drug loading was calculated by TGA analysis (16.97%). Drug release profiles of PEG-PAMAM G4-FA-5FU- 99m Tc and PEG-PAMAM G4-FA-5FU were evaluated. The radiochemical purity of PEG-PAMAM G4-FA-5FU- 99m Tc and PEG-PAMAM G4-FA- 99m Tc was obtained at >95% with excellent in-vitro and in-vivo stabilities. PEG-PAMAM G4-FA-5FU- 99m Tc was synthesized and the stability studies were carried out by the ITLC methods in serum (86.67% and 83.75%) and PBS. Combinational therapy effects of 5-FU and 99m Tc containing nano-complexes were evaluated on 4 T1 (mouse breast cancer) and MDA-MB-231 (human breast adenocarcinoma) cancer cell lines. Excellent uptake values were obtained for FA-decorated nano-complexes on 4 T1 and MDA-MB-231 cell lines. Subsequently, tumor inhibition effects of PEG-PAMAM G4-FA-5FU- 99m Tc and PEG-PAMAM G4-FA-5FU were evaluated using the breast tumor-bearing BALB/C mice. Graphical abstract Breast Tumor Targeting with PAMAM-PEG-5FU- 99m Tc As a New Therapeutic Nanocomplex: in In-vitro and In-vivo Studies was presented. This targeted drug delivery system can significantly increase the efficiency of cancer therapy, and reduce the treatment cost and time.

Gold nanoparticles (AuNPs) are considered valuable nanomaterials for the design of radiolabeled nanoprobes for single-photon emission computed tomography (SPECT) imaging. Radiolabeled and functionalized AuNPs could improve lymphatic mapping by enhancing the radioactive signaling of individual particles in the sentinel node. In this study, an alternative method for functionalizing commercial AuNps with mannose is described. The chemical derivatization and biofunctionalization of AuNPs were performed with lipoic acid and mannose, respectively. Several levels of mannose were tested; the thiolate hydrazinonicotinamide-glycine-glycine-cysteine (HYNIC) molecule was also used for 99m Tc radiolabeling. Physicochemical characterization of this system includes U-V spectroscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, and transmission electron microscopy. The most stable nanoprobe, in terms of the aggregation, radiolabeling efficiency, and purity, was tested in a sentinel lymph node model in a rat by microSPECT/computed tomography (CT) imaging. The SPECT images revealed that 99m Tc-radiolabeled AuNPs functionalized with mannose can track and accumulate in lymph nodes in a similar way to the commercial 99m Tc-Sulfur colloid, commonly used in clinical practice for sentinel lymph node detection. These promising results support the idea that 99m Tc-AuNPs-mannose could be used as a SPECT contrast agent for lymphatic mapping.

Breast cancer is the most common type of cancer in women worldwide. There have been many efforts for early breast cancer detection and among them molecular imaging have been extremely of high importance. Single-photon emission computed tomography (SPECT/CT) is a kind of imaging technique able to reveal crucial information with using radiopharmaceuticals. In this study, Technetium-99m-(DOTA-NHS-ester)-Methionine radiopharmaceutical was synthesized. Between 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-HNS ester) (MACROCYCLICS, DOTA-NHS ester, Plano, Texas, USA) and methionine(marker) were conjugated. The DOTA-HNS ester-Methionine was labeled with Technetium-99m (Inter-Medical, Technetium-99m, Bergamo, Italy). The synthesized radiopharmaceutical was used in SPECT/CT imaging for breast cancer diagnosis. For radiopharmaceutical evaluation, MTT assay for cellular toxicity, biodistribution, cellular uptake and radiochemical purity were employed.Technetium-99m-(DOTA-NHS-ester)-Methionine radiochemical had less cellular toxicity in human embryonic kidney cells 293 cell line (HEK293). Cellular uptake was indicated higher percent with use of Methionine as a marker, and radiochemical purity was high. Based on the results Technetium-99m-(DOTA-NHS-ester)-Methionine radiochem may be a better option for early detection of breast cancer. Further study is recommended to confirm these findings in clinical practice., (Copyright © 2019. Published by Elsevier B.V.)

Background: 99mTc is a radioactive isotope that is obtained by eluting a 99Mo/99mTc generator. (PINSTECH, Islamabad) and used for radionuclide scanning., Objectives: The objective of this work is to study the uncertainties in 99mTc activity that exist due to time delay between injection preparation and administration to patients, during the process of gamma camera scanning., Methods: Lead canisters were used for storing elution vials and dose calibrator for measuring 99mTc activity in mCi. The activity of preparing 99mTc injection and its administration to patients were compared with the prescribed values of activity recommended in the Society of Nuclear Medicine procedure guidelines., Results: This study showed that uncertainty in the activity existed in one thyroid patient, 38 bone patients, 5 renal patients and 45 cardiac patients., Conclusion: This uncertainty in activity exists due to time delay between injection preparation and administration to patients, as well as due to residual radionuclide that is not injected into patients and remains in the syringe., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)

This paper presents the results of measurements of 99m Tc activity concentrations in indoor air in a nuclear medicine department and resulting estimated 99m Tc intake by medical personnel. 99m Tc air activity measurements were conducted at the Nuclear Medicine Department, John Paul II Hospital, Krakow, Poland, during ventilation-perfusion SPECT lung scans. Technetium from the air was collected by means of a mobile aerosol sampler with a Petryanov filter operating at an average flow rate of 10 dm 3  min -1 . Measured activities ranged from 99 ± 11 to 6.1 ± 0.5 kBq m -3 . The resulting daily average intake of 99m Tc by medical staff was estimated to be 5.4 kBq, 4.4 kBq, 3.0 kBq and 2.5 kBq, respectively, for male technicians, female technicians, male nurses and female nurses. Corresponding annual effective doses were 1.6 µSv for technicians and 1 µSv for nurses. The highest equivalent dose values were determined for extrathoracic (ET) airways: 5 µSv and 10 µSv for nurses and technicians, respectively. It is concluded that estimated annual absorbed doses are over three orders of magnitude lower than the dose limit established in the Polish Atomic Law Act and in recommendations of the International Commission on Radiological Protection for medical staff.

Interleukin (IL)-15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL-15 antagonist peptide named [K6T]P8, with potential therapeutic application in RA. In the current work, the metabolic stability of this peptide in synovial fluids from RA patients was studied. Moreover, [K6T]P8 peptide was labeled with 99m Tc to investigate its stability in human plasma and its biodistribution pattern in healthy rats. The biological activity of [K6T]P8 peptide and its dimer was evaluated in CTLL-2 cells, using 3 different additives to improve the solubility of these peptides. The half-life of [K6T]P8 in human synovial fluid was 5.88 ± 1.73 minutes, and the major chemical modifications included peptide dimerization, cysteinylation, and methionine oxidation. Radiolabeling of [K6T]P8 with 99m Tc showed a yield of approximately 99.8%. The 99m Tc-labeled peptide was stable in a 30-fold molar excess of cysteine and in human plasma, displaying a low affinity to plasma proteins. Preliminary biodistribution studies in healthy Wistar rats suggested a slow elimination of the peptide through the renal and hepatic pathways. Although citric acid, sucrose, and Tween 80 enhanced the solubility of [K6T]P8 peptide and its dimer, only the sucrose did not interfere with the in vitro proliferation assay used to assess their biological activity. The results here presented, reinforce nonclinical characterization of the [K6T]P8 peptide, a potential agent for the treatment of RA and other diseases associated with IL-15 overexpression., (Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.)

To analyze erythropoietin receptor (EpoR) status in tumors, recombinant human erythropoietin (rHuEpo) was labeled with 99m Tc by 99m Tc-centered 1-pot synthesis, resulting in high radiochemical purity, stability, and biological activity. Both in vitro cell culture experiments and biodistribution studies of normal rats demonstrated successful EpoR targeting. The biodistribution of labeled rHuEpo in a NCI-H1975 xenograft model showed tumor accumulation (tumor-to-muscle ratio, 4.27 ± 1.77), confirming the expression of active EpoR in tumors. Thus, as a novel single positron emission computerized tomography tracer for the imaging of EpoR expression in vivo, 99m Tc-rHuEpo is effective for exploring the role of EpoR in cancer growth, metastasis and angiogenesis., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Mesoporous nanoparticles have a great potential in targeted therapy approaches due to their ideal properties for encapsulation of various drugs, proteins and also biologically active molecules., Material and Methods: We used mesoporous hydroxyapatite (HA) nanoparticles as a drug carrier and developed radiolabeled mesoporous HA containing of 2-deoxy-D-glucose (2DG) and Doxorubicin (DOX) with technetium-99m (99mTc) for imaging in in vitro and in vivo studies., Results: 2DG and DOX in presence of mesoporous HA nanoparticles more reduced the fraction of viable cells in the MDA-MB-231, MCF-7 human and MC4-L2 Balb/c mice breast cancer cells. The radiochemical purity of the nano-2DG-DOX complex with 99mTc was calculated to 96.8%. The results of cellular uptake showed a 44.77% increase in uptake of the [99mTc]-nano-2DG-DOX compared to the complex without nanoparticles (p < 0.001)., Conclusion: Radioisotopic imaging demonstrated a high biochemical stability for [99mTc]-nano-2DG-DOX complex. The results demonstrated that [99mTc]-nano-2DG-DOX, may be used as an attractive candidate in cancer imaging and treatment managing.

Technetium (99mTc)-radiolabeled colloids are popular tracers used to map lymphatic vessels and regional lymph nodes (LNs). The regional LN status is a significant determinant of cancer stage and patient prognosis, and strongly influences treatment. Regional LN dissection has become a part of surgical treatment. However, not all patients with LN involvement benefit from extensive lymphadenectomy in terms of prolonged survival. Moreover, overtreatment of patients with localized disease carries the unnecessary risk of complications. It is believed that sentinel LN biopsy (SLNB) allows to assess the involvement of the most representative LN of the lymphatic basin and to decide on radical LN dissection.99mTc is an easily available radionuclide emitting gamma rays. The value of 99mTc for diagnostic procedures is associated with its relatively short half-life that makes it safe both for patients and medical personnel. A colloid presenting specific physical and biological properties, including optimal particle size, is a carrier for the radionuclide. When administered at the tumor site, a radiocolloid is absorbed by the lymphatics, and the first LN that it gets trapped in is referred to as the sentinel LN (SLN). The radiopharmaceutical must reach the SLN relatively quickly, but its storage within the SLN, and the radionuclide's half-life must be long enough to enable intraoperative imaging and evaluation. SLNB is currently the gold standard in breast cancer and malignant melanoma diagnosis, and is under extensive investigation in gynecological cancers. Here, we provide a historical perspective of the SLN concept and the clinical relevance of SLNB in gynecologic oncology. Moreover, we review the technical aspects of the application of 99mTc-based radiopharmaceuticals in lymphoscintigraphy and intraoperative lymphatic mapping., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Breast cancer is a malignant disease with high mortality rate among women in the world. It is necessary to diagnose breast cancer at the early stage before it metastasizes in patients., Objective: The aim of this study is the evaluation of 99mTc-(tricine)-HYNIC-Lys-FROP for breast tumor imaging., Method: Lys-FROP peptide was labeled with 99mTc using HYNIC as chelator and tricine as co-ligand. Specific binding of this radiolabeled peptide on breast cancerous cell was assessed in different cell lines as well as in tumor-bearing mice., Results: HYNIC-Lys-FROP peptide was labeled with 99mTc at radiochemical purity more than 99%. It was observed high stability in normal saline and serum about 95%. The highest cellular uptake was observed in MCF-7 breast tumor cells treated with 99mTc-(tricine)-HYNIC-Lys-FROP as compared to other cell lines (lung, ovarian, T47D breast cancer cell lines). Biodistribution results in female MCF-7 tumor-bearing mice showed the relatively high tumor uptake and tumor-muscle ratio as 3.82 ± 0.66 after 15 min post-injection of 99mTc-(tricine)- HYNIC-Lys-FROP. Tumor uptake was reduced in mice that were co-injected with excess of unlabeled peptide to be 0.91 ± 0.08., Conclusion: Findings showed this radiolabeled peptide is a promising candidate for tumor targeting and molecular imaging of breast cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Calcium chloride is an essential calcium channel agonist which plays an important role in the contraction of muscles by triggering calcium channel. First time hypothesized about its role in the treatment of GER (gastro-esophageal reflux) and vomiting disorder due to its local action. There are two objectives covered in this study as first, the development and optimization of floating formulation of calcium chloride and another objective was to evaluate optimized formulation through gamma scintigraphy in human subjects. Gastro retentive formulation of calcium chloride was prepared by direct compression method. Thirteen tablet formulations were designed with the help of sodium chloride, HPMC-K4M, and carbopol-934 along with effervescing agent sodium bicarbonate and citric acid. Formulation (F8) fitted best for Korsmeyer-Peppas equation with an R 2 value of 0.993. The optimized formulation was radiolabelled with 99m Tc-99 m pertechnetate for its evaluation by gamma scintigraphy. Gastric retention (6 h) was evaluated by gamma scintigraphy in healthy human subjects and efficacy of present formulation confirmed in GER positive human subjects. Gamma scintigraphy results indicated its usefulness in order to manage GERD. Stability studies of the developed formulation were carried out as per ICH guidelines for region IV and found out to be stable for 24 months.

99m Tc, the most common radioisotope used in nuclear medicine, is produced in a nuclear reactor from the decay of 99 Mo. There are only a few aging nuclear reactors around the world that produce 99 Mo, and one of the major contributors, the National Research Universal (Canada), ceased production on October 31, 2016. The National Research Universal produced approximately 40% of the world's 99 Mo supply, so with its shut down, shortages of 99 Mo/ 99m Tc are expected. Methods: Nuclear pharmacies and nuclear medicine departments throughout the United States were contacted and asked to provide their strategies for coping with a shortage of 99 Mo/ 99m Tc. Each of these strategies was evaluated on the basis of its effectiveness for conserving 99m Tc while still meeting the needs of the patients. Results: From the responses, the following 6 categories of strategies, in order of importance, were compiled: contractual agreements with commercial nuclear pharmacies, alternative imaging protocols, changes in imaging schedules, software use, generator management, and reduction of ordered doses or elimination of backup doses. Conclusion: The supply chain of 99 Mo/ 99m Tc is quite fragile; therefore, being aware of the most appropriate coping strategies is crucial. It is essential to build a strong collaboration between the nuclear pharmacy and nuclear medicine department during a shortage situation. With both nuclear medicine departments and nuclear pharmacies implementing viable strategies, such as the ones proposed, the amount of 99m Tc available during a shortage situation can be maximized., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m ((99m)Tc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with (99m)Tc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner.

Purpose: Noninvasive quantification of chemokine receptor 4 (CXCR4) expression could serve as a prognostic indicator and may be of value for the design of personalized therapies and posttreatment monitoring. The objective of the present study was to assess the use of (99m)Tc-radiolabeled small-interference RNA (siRNA) targeting CXCR4 to detect CXCR4 expression in vivo., Procedures: CXCR4 siRNAs were radiolabeled with (99m)Tc using the bifunctional chelator hydrazinonicotinamide (HYNIC), and the labeling efficiency, specific activity and radiochemical purity were determined. The stability of the probe in serum was assessed by measuring its radiochemical purity and inhibitory activity by RT-PCR and western blotting. Biodistribution studies and static imaging were performed in MDA-MB-231 tumor-bearing mice., Results: Radiochemical purity remained highly stable in PBS and fresh human serum at room temperature and at 37 °C. Radiolabeled siRNA1 showed strong inhibitory effects similar to those of unlabeled siRNA1 on both CXCR4 messenger RNA (mRNA) and protein in vitro. The excretion of the probe occurred mainly through the liver and kidneys. Tumors were clearly visualized at 1-10 h after injection of the probe, but not after injection of the control probe., Conclusions: (99m)Tc-labeled CXCR4 siRNA1 shows tumor-specific accumulation and could be a promising strategy for the visualization of CXCR4 expression in human breast cancer.

Objective: Simultaneous acquisition of (99m)Tc and (123)I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors., Methods: 10-ml cylindrical syringes contained about 37 MBq (99m)Tc-tetrofosmin ((99m)Tc-TF) or 37 MBq (123)I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid ((123)I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP to assess the influence of (99m)Tc upscatter and (123)I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. Two 1-ml syringes contained 105 MBq (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) and 35 MBq (123)I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ((123)I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq (99m)Tc-HMPAO and 35 MBq (123)I-FP-CIT., Results: The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of (123)I-BMIPP exhibited fewer radioactive counts for 300 MBq (99m)Tc-TF without scatter correction (SC) in 125-150 keV. There was no upscatter contamination of (99m)Tc-TF in 150-175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq (99m)Tc-TF without SC in 125-150 keV. In the rats, myocardial images and radioactive counts of (99m)Tc-TF with the dual tracer were identical to those of the (99m)Tc-TF single injection. Downscatter contamination of (123)I-FP-CIT was 4.2 % without SC in 125-150 keV. In the first injection of (99m)Tc-HMPAO and second injection of (123)I-FP-CIT, brain images and radioactive counts of (99m)Tc-HMPAO with the dual tracer in normal mice also were the similar to those of the (99m)Tc-HMPAO single injection. In the first injection of (123)I-FP-CIT and second injection of (99m)Tc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the (123)I-FP-CIT single injection., Conclusions: Dual-tracer imaging of (99m)Tc- and (123)I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of (99m)Tc-labeled radiotracers relative to (123)I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of (99m)Tc- and (123)I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.

Purpose: We investigated the usefulness of [(99m)Tc]duramycin for monitoring early response to cancer therapy in mice, with an eye towards clinical translation., Procedures: [(99m)Tc]Duramycin was injected in healthy CD1-/- mice to estimate human [(99m)Tc]duramycin radiation dose. [(99m)Tc]Duramycin single-photon emission computed tomography (SPECT) imaging of apoptosis was evaluated in a mouse model of colorectal cancer treated with irinotecan and validated ex vivo using autoradiography, cleaved caspase-3, and TdT-mediated dUTP nick-end labeling (TUNEL) histology of the tumors., Results: The mean effective dose was estimated to be 3.74 × 10(-3) ± 3.43 × 10(-4) mSv/MBq for non-purified and 3.19 × 10(-3) ± 2.16 × 10(-4) mSv/MBq for purified [(99m)Tc]duramycin. [(99m)Tc]Duramycin uptake in vivo following therapy increased significantly in apoptotic irinotecan-treated tumors (p = 0.008). Radioactivity in the tumors positively correlated with cleaved caspase-3 (r = 0.85, p < 0.001) and TUNEL (r = 0.92, p < 0.001) staining., Conclusion: [(99m)Tc]Duramycin can be used to detect early chemotherapy-induced tumor cell death, and thus, may be a prospective candidate for clinical SPECT imaging of tumor response to therapy.

Purpose: Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m labelled Cbl derivative ([(99m)Tc]PAMA(4)-Cbl) for targeting infections caused by Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed by biodistribution studies in a mouse model of foreign body infection., Procedures: E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test strains. [(57)Co]Cbl, [(67)Ga]citrate and [(99m)Tc]DTPA served as reference compounds. The in vitro competitive binding of [(57)Co]Cbl or [(99m)Tc]PAMA(4)-Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 °C. A cage mouse model of infection was used for biodistribution of intravenous [(57)Co]Cbl and [(99m)Tc]PAMA(4)-Cbl in cage and dissected tissues of infected and non-infected mice., Results: Maximum binding (mean ± SD) of [(57)Co]Cbl to viable E. coli was 81.7 ± 2.6 % and to S. aureus 34.0 ± 6.7 %, at 37 °C; no binding occurred to heat-killed bacteria. Binding to both test strains was displaced by 100- to 1000-fold excess of unlabeled Cbl. The in vitro binding of [(99m)Tc]PAMA(4)-Cbl was 100-fold and 3-fold lower than the one of [(57)Co]Cbl for E. coli and S. aureus, respectively. In vivo, [(99m)Tc]PAMA(4)-Cbl showed peak percentage of injected dose (% ID) values between 1.33 and 2.3, at 30 min post-injection (p.i.). Significantly higher retention occurred in cage fluids infected with S. aureus at 4 h and with E. coli at 8 h p.i. than in non-infected animals. Accumulation into infected cages was also higher than the one of [(99m)Tc]DTPA, which showed similar biodistribution in infected and sterile mice. [(57)Co]Cbl gradually accumulated in cages with peaks % ID between 3.58 and 4.83 % achieved from 24 to 48 h. Discrimination for infection occurred only in E. coli-infected mice, at 72 h p.i. [(67)Ga]citrate, which showed a gradual accumulation into cage fluids during 12 h, was discriminative for infection from 48 to 72 h p.i. (P < 0.05)., Conclusion: Cbl displayed rapid and specific in vitro binding to test strains. [(99m)Tc]PAMA(4)-Cbl was rapidly cleared from most tissues and discriminated between sterile and infected cages, being a promising candidate for imaging infections in humans.

Objective: Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target which has been used for melanoma imaging and therapy. In this work, a new lactam bridge α-MSH analog was labeled with (99m)Tc via HYNIC and EDDA/tricine as coligands including gamma aminobutyric acid (GABA) as a three carbon chain spacer between HYNIC and the N-terminus of the cyclic peptide. Also, stability in human serum, receptor bound internalization, in vivo tumor uptake, and tissue biodistribution were thoroughly investigated., Methods: HYNIC-GABA-Nle-CycMSHhept was synthesized using a standard Fmoc strategy. Labeling was performed at 95 °C and analysis involved instant thin layer chromatography and high performance liquid chromatography methods. The receptor bound internalization rate was studied in MC1 receptor expressing B16/F10 cells. Biodistribution of radiopeptide was studied in nude mice bearing B16/F10 tumor., Results: Labeling yield of >98 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed efficient stability in the presence of human serum. The radioligand showed specific internalization into B16/F10 cells (12.45 ± 1.1 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor-positive organs so that after 2 h the uptake in mouse tumor was 5.10 ± 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 ± 0.68 % ID/g at 2 h after injection)., Conclusions: The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors.

Chemistry is the science of chemical reactions, the study of chemical properties, composition, and structure of a molecule. When the molecule under observation is of a biological origin (proteins, carbohydrates, lipids, or nucleic acids), the study of its chemical properties, reactions, and structure is known as biochemistry. Similarly, if the molecule or a biochemical under observation is radioactive, the science becomes radiochemistry or radio biochemistry. So, chemistry is the science which fuses these two diverse fields of applied sciences. Fusion of these two sciences on chemistry platform has enabled the development of various new radioactive formulations which are called as radiopharmaceuticals and are being used the world over for clinical as well as experimental purposes. For the successful development of radiopharmaceuticals, we require in-depth understanding of both biochemistry as well as radiochemistry. So, the present review article summarizes basic relevant details and experimental advances in both these sciences with regard to development of radiopharmaceuticals.

The history of the early identification of elements and their designation to the Mendeleev Table of the Elements was an important chapter in German science in which Ida (1896-1978) and Walter (1893-1960) Noddack played an important role in the first identification of rhenium (element 75, 1925) and technetium (element 43, 1933). In 1934 Ida Noddack was also the first to predict fission of uranium into smaller atoms. Although the Noddacks did not for some time later receive the recognition for the first identification of technetium-99m, their efforts have appropriately more recently been recognized. The discoveries of these early pioneers are even more astounding in light of the limited technologies and resources which were available during this period. The Noddack discoveries of elements 43 and 75 are related to the subsequent use of rhenium-188 (beta/gamma emitter) and technetium-99m (gamma emitter) in nuclear medicine. In particular, the theranostic relationship between these two generator-derived radioisotopes has been demonstrated and offers new opportunities in the current era of personalized medicine.

In this study, a novel way of distinguishing the intrinsic relationship between ανβ3 integrin targeting and detection of tumor growth by using a radiolabeled tracer based on a cyclic Arg-Gly-Asp (RGD) peptide was provided. The potential of the in vivo scintigraphic imaging of the developing vasculature from the early stage of tumor growth was evaluated. Alongside with the scintigraphic images, biodistribution studies were performed at distinct time points to validate this noninvasive imaging approach. The ability to noninvasively assess the tumor growth of ανβ3 integrin-positive glioblastoma tumors provides a method to better understand tumor angiogenesis in vivo and allows for a direct assessment of anti-integrin treatment efficacy.

Unlabelled: A bacterial endotoxin test (BET) is required to detect or quantify bacterial endotoxin that may be present in radiopharmaceutical preparations. The test uses Limulus amebocyte lysate, which, in the presence of bacterial endotoxin and divalent calcium ions, causes the formation of a coagulin gel. (99m)Tc-labeled radiopharmaceuticals have chelating ligands such as diethylene triamine pentaacetic acid (DTPA), ethylene dicysteine (EC), L,L-ethyl cysteinate dimer (ECD), N-[2,4,6-trimethyl-3 bromoacetanilid] iminodiacetic acid (mebrofenin), dimercapto succinic acid-III (DMSA-III), dimercapto succinic acid-V (DMSA-V), and several others, which form a coordination complex with Na-(99m)Tc-O4 in the presence of reducing agents. During BET by the gel-clot method, the free sulfhydryl (-SH) and carboxyl (-COOH) in some of the chelating agents in the final (99m)Tc-labeled radiopharmaceuticals decrease the free divalent calcium ion concentration, which in turn inhibits coagulin gel formation. This study was designed using the premise that addition of calcium chloride solution to the reaction mixture would nullify this effect., Methods: We present here the data obtained from BET assay analysis of (99m)Tc-labeled radiopharmaceuticals and the cold kits from which they are made (EC, ECD, methoxyisobutylisonitrile, DTPA, mebrofenin, methylene diphosphonic acid [MDP], DMSA-III, and DMSA-V) using 2 different dilutions, maximum valid dilution (MVD) and half maximum valid dilution (MVD/2), with and without the addition of calcium chloride at a final concentration of 300 μM., Results: It was observed that at MVD and MVD/2 all of the (99m)Tc-labeled kits exhibited interference in coagulin gel formation with the exception of (99m)Tc-methoxyisobutylisonitrile, (99m)Tc-MDP, (99m)Tc-mebrofenin, and (99m)Tc-ECD. However, only the cold kits of methoxyisobutylisonitrile and MDP did not show inhibition. An addition of calcium chloride solution nullified this interference at both MVD and MVD/2 in all of the (99m)Tc-labeled radiopharmaceuticals in which interference was observed., Conclusion: In practice, Limulus amoebocyte lysate testing is not a method of choice for (99m)Tc-labeled radiopharmaceuticals because these radiopharmaceuticals exhibit interference. However, our study proves the hypothesis that the addition of calcium chloride can circumvent this problem. The addition of calcium chloride provides an enhanced biologic quality control testing option for the final formulation of (99m)Tc-labeled radiopharmaceuticals at the hospital radiopharmacy end., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: (99m)Tc is currently produced by an aging fleet of nuclear reactors, which require enriched uranium and generate nuclear waste. We report the development of a comprehensive solution to produce (99m)Tc in sufficient quantities to supply a large urban area using a single medical cyclotron., Methods: A new target system was designed for (99m)Tc production. Target plates made of tantalum were coated with a layer of (100)Mo by electrophoretic deposition followed by high-temperature sintering. The targets were irradiated with 18-MeV protons for up to 6 h, using a medical cyclotron. The targets were automatically retrieved and dissolved in 30% H2O2. (99m)Tc was purified by solid-phase extraction or biphasic exchange chromatography., Results: Between 1.04 and 1.5 g of (100)Mo were deposited on the tantalum plates. After high-temperature sintering, the (100)Mo formed a hard, adherent layer that bonded well with the backing surface. The targets were irradiated for 1-6.9 h at 20-240 μA of proton beam current, producing up to 348 GBq (9.4 Ci) of (99m)Tc. The resulting pertechnetate passed all standard quality control procedures and could be used to reconstitute typical anionic, cationic, and neutral technetium radiopharmaceutical kits., Conclusion: The direct production of (99m)Tc via proton bombardment of (100)Mo can be practically achieved in high yields using conventional medical cyclotrons. With some modifications of existing cyclotron infrastructure, this approach can be used to implement a decentralized medical isotope production model. This method eliminates the need for enriched uranium and the radioactive waste associated with the processing of uranium targets., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Epidermal growth factor receptor (EGFR) is overexpressed in many carcinomas and remains a prime target for diagnostic and therapeutic applications. There is a need to develop noninvasive methods to identify the subset of patients that is most likely to benefit from EGFR-targeted treatment. Noninvasive imaging of EGFR messenger RNA (mRNA) expression may be a useful approach. The aim of this study was to develop a method for preparation of single-photon-emitting probes, (99m)Tc-labeled EGFR mRNA antisense peptide nucleic acid (PNA) ((99m)Tc-EGFR-PNA), and nontargeting control ((99m)Tc-CTL-PNA) and to evaluate their feasibility for imaging EGFR mRNA overexpression in malignant tumors in vivo., Methods: On the 5' terminus of synthesized single-stranded 17-mer antisense EGFR mRNA antisense PNA and mismatched PNA, a 4-amino-acid (Gly-(D)-Ala-Gly-Gly) linker forming an N4 structure was used for coupling (99m)Tc. Probes were labeled with (99m)Tc by ligand exchange. The radiochemical purity of these (99m)Tc-labeled probes was determined by reversed-phase high-performance liquid chromatography. Cellular uptake, retention, binding specificity, and stability of the probes were studied either in vitro or in vivo. Biodistribution and radionuclide imaging were performed in BALB/c nude mice bearing SKOV3 (EGFR-positive) or MDA-MB-435S (EGFR-negative) carcinoma xenografts, respectively., Results: The average labeling efficiencies of (99m)Tc-EGFR-PNA and (99m)Tc-CTL-PNA were 98.80% ± 1.14% and 98.63% ± 1.36% (mean ± SD, n = 6), respectively, within 6 h at room temperature, and the radiochemical purity of the probes was higher than 95%. (99m)Tc-EGFR-PNA was highly stable in normal saline and fresh human serum at 37°C in vitro and in urine and plasma samples of nude mice after 2-3 h of injection. Cellular uptake and retention ratios of (99m)Tc-EGFR-PNA in SKOV3 cells were higher than those of (99m)Tc-CTL-PNA and the EGFR-negative control. Meanwhile, EGFR mRNA binding (99m)Tc-EGFR-PNA was blocked with an excess of unlabeled EGFR-PNA in SKOV3 cell lines. The biodistribution study demonstrated accumulation of (99m)Tc-EGFR-PNA primarily in the SKOV3 xenografts and in EGFR-expressing organs. Radionuclide imaging demonstrated clear localization of (99m)Tc-EGFR-PNA in the SKOV3 xenografts shortly after injection but not in (99m)Tc-CTL-PNA and the EGFR-negative control., Conclusion: (99m)Tc-EGFR-PNA has the potential for imaging EGFR mRNA overexpression in tumors., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Four (99m)Tc-labeled chalcone derivatives and their corresponding rhenium analogues were tested as potential probes for imaging β-amyloid plaques. The chalcones showed higher affinity for Aβ(1-42) aggregates than did (99m)Tc complexes. In sections of brain tissue from an animal model of AD, the four Re chalcones intensely stained β-amyloid plaques. In biodistribution experiments using normal mice, (99m)Tc-BAT-chalcone ([(99m)Tc]17) displayed high uptake in the brain (1.48% ID/g) at 2 min postinjection. The radioactivity washed out from the brain rapidly (0.17% ID/g at 60 min), a highly desirable feature for an imaging agent. [(99m)Tc]17 may be a potential probe for imaging β-amyloid plaques in Alzheimer's brains.

Introduction: Prostate cancer (PCa) is the second most frequent cancer diagnosis in men and the fifth leading cause of death worldwide. Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) receptors are overexpressed in PCa. In this study, we have developed iron oxide nanoparticles (IONs) functionalized with the Prostate Specific Membrane Antigen (PSMA) and Gastrin Releasing Peptide (GRP) ligands for dual targeting of Prostate cancer. Methods: IONs were developed with a thin silica layer on their surface with MPTES (carrying -SH groups, IONs-SH), and they were coupled either with a pharmacophore targeting PSMA (IONs-PSMA) or with bombesin peptide (IONs-BN), targeting GRP receptors, or with both (IONs-PSMA/BN). The functionalized IONs were characterized for their size, zeta potential, and efficiency of functionalization using dynamic light scattering (DLS) and Fourier-Transform Infrared Spectroscopy (FT-IR). All the aforementioned types of IONs were radiolabeled directly with Technetium-99m (99mTc) and evaluated for their radiolabeling efficiency, stability, and binding ability on two different PCa cell lines (PC3 and LNCaP). Results and Discussion: The MTT assay demonstrated low toxicity of the IONs against PC3 and LNCaP cells, while the performed wound-healing assay further proved that these nanostructures did not affect cellular growth mechanisms. The observed hemolysis ratio after co-incubation with red blood cells was extremely low. Furthermore, the 99mTc-radiolabeled IONs showed good stability in human serum, DTPA, and histidine, and high specific binding rates in cancer cells, supporting their future utilization as potential diagnostic tools for PCa with Single Photon Emission Computed Tomography (SPECT) imaging. [ABSTRACT FROM AUTHOR]

Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn− lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn− tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery. [ABSTRACT FROM AUTHOR]

Background: Non-invasive monitoring of human epidermal growth factor receptor 2 (HER2) status in malignant lesions of breast cancer patients has been established in clinical positron emission computed tomography (PET). Objectives: In this study, we try to evaluate the feasibility of 99mTc-labeled affibody in monitoring HER2 expression for breast cancer patients using single-photon emission computed tomography (SPECT) apparatus fused with a conventional CT scanner (SPECT/CT). Patients and Methods: HER2 affibody with endogenous chelating site was recombinantly expressed and purified. 99mTc was added to HER2 affibody at carboxyl-terminal cystein site specifically. Breast cancer patients were enrolled for whole-body SPECT/CT imaging following intravenous administration of 99mTc-labeled HER2affibody. Regions of interest were drawn manually over tumor sites and the normal surrounding muscle. The HER2 status of breast cancer lesions was determined by post-surgical immunohistochemistry, and correlated with the uptake of 99mTc-labeled affibody as measured by SPECT. Results: Administration of 99mTc-labeled HER2 affibody was well tolerated by all patients without noticeable adverse side effects. 99mTc-labeled affibody SPECT imaging clearly visualized HER2 positive breast cancer lesions at approximately 1.5 and 4.5 hours after affibody treatment. The tumor to background (T/B) ratios of locally hot breast cancer lesions by HER2 imaging were closely related to post-surgical HER2 expression levels of cancer tissues by immunohistochemistry. When the tumor: muscle ratio exceeded 2.4 (cutoff value) in transverse imaging, the tumor lesion was considered to be HER2-positive arbitrarily. The diagnostic sensitivity of 99mTc-labeled affibody SPECT/CT in identifying HER2 positive breast cancer was 80 percent (12/15), while the specificity and accuracy of 99mTc-labeled affibody SPECT/CT were 60 percent (9/15) and 70 percent (21/30) respectively. In tumors with a diameter greater than 12 mm, the sensitivity of 99mTc-labeled affibody SPECT/CT was 100 percent (12/12). Conclusion: 99mTc-labeled affibody SPECT/CT may find utility in evaluating HER2 expression in breast cancer patients, and may provide new modality for guiding HER2 targeted therapy complementary to biopsy in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Integrins are interesting targets in oncology. RGD sequence has high affinity for αVβ3 integrin receptors. Diagnostic/therapeutic agents can be selectively delivered into cancer cells overexpressing αVβ3 integrin by using RGD as a carrier. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown anticancer properties in in vitro and in vivo studies. The anti-cancer properties of NSAIDs occur though COX-2 inhibition. Regarding the anti-cancer properties of NSAIDs and overexpression of COX-2 enzyme in cancer cells, targeted delivery of NSAIDs into cancer cells to maximize their efficiency and minimize their side effects may gain increased clinical interest. Objectives: In this study, RGD was conjugated to ketoprofen/Naproxen to selectively transfer these non-selective COX inhibitors into cancer cells. Methods: Keto/Nap-RGD-N4 peptides were synthesized based on solid phase fmoc peptide synthesis. Radiolabeling with [99mTc] via N4 (GGAG) ligand was done for biological evaluation. Affinity and specificity of Keto/Nap-RGD-N4 to integrin was determined using A2780, OVCAR-3, SKOV-3 and HT-1080 cell lines. Percentage of Intenalization was measured in A2780 cells. Biodistriburion was studied in normal and tumor model mice. Results: Radiolabeled compounds showed high affinity to cells expressing αVβ3 integrin in comparison to cells not expressing αVβ3. The affinity to A2780 was significantly higher than OVCAR-3 cells. The %internalization into A2780 cells was quite low. Compounds showed more than 50% inhibition on A2780 and OVCAR-3 cells, less than 10% on MCF-7 and HT-1080 cells and no cytotoxicity on fibroblast cells after 48 h incubation. Although uptake of radiolabeled compounds in tumor was high at 1 h post-injection, the tumor/blood ratio was less than 1.5 which made SPECT imaging impossible. Conclusion: Provided that NSAID drugs are conjugated to RGD, there will be a selective delivery to target tissues as well as synergetic anti-tumor effects which reduce systemic doses and toxicity. [ABSTRACT FROM AUTHOR]

In this study, we introduce a new 99mTc-radiolabeled bombesin derivative for imaging of prostate cancer (PC). We used 6-hydrazinonicotinamide (HYNIC) as bi-functional chelating agent and tricine/ethylenediamine diacetic acid (EDDA) as an exchange co-ligands. Radiolabeling was achieved with high purity and was accompanied with high solution and serum stability. Cellular binding study demonstrated specific binding and internalization of radioconjugate in cultured PC3 cells. In vivo experiments showed fast blood clearance with kidney excretion. Blocking experiments showed decreased uptake of radiopeptide in tumor and pancreas. The results of the imaging using planar SPECT also confirmed suitable tumour uptake for PC3 xenograft nude mice. [ABSTRACT FROM AUTHOR]

It has been shown that more than 75% of ductal pancreatic adenocarcinomas overexpressed neurotensin ( NT) receptors. Overexpression of NT receptors has been reported in various human tumor types. Hence, a non-invasive diagnosis and staging method could be very beneficial. In this work, we describe radiolabeling and evaluation of new neurotensin analogues to target neurotensin receptor-positive tumors such as pancreatic carcinoma. Radiolabeling was performed at 95°C for 10 min using 99mTc in the presence of tricine/ EDDA exchange labeling. Radiochemical yield analysis involved ITLC and HPLC methods. A binding assay test was carried out in nine different concentrations of labeled neurotensin analogues in HT-29 cells. Radiopeptide-specific binding and internalization were studied in NT receptors expressing HT-29 cells. Biodistribution studies were performed in tumor-free BALB/c mice and HT-29 xenografted tumor-bearing nude mice. The peptide was efficiently labeled by 99mTc with high radiochemical yields (>98%). The radioconjugate was thoroughly stable in the solution and human serum even for 24 hr. The radiolabeled peptide showed high affinity (32.66 ± 4.01 n m) and specificity internalization (>%18 after 4 hr) to HT-29 cells. The radiopeptide efficiently showed tumor size and location in tumor-bearing nude mice. In biodistribution, a receptor-specific uptake of radiopeptide was observed in neurotensin receptor-positive organs such as intestine. Uptake in the tumor was 4.59 ± 0.23% ID/g after 2 hr. Owing to excellent stability, high affinity, rapid blood clearance, low accumulation in non-target organs, and high uptake in tumor, the 99mTc- HYNIC-peptide is a potential agent for targeting of NTR-overexpressing tumor cells in clinical surroundings. When successfully executed in the clinical surrounding, non-invasive imaging of NTR-positive tumors with 99mTc-labeled new neurotensin analogues could facilitate therapy procedure and monitoring. [ABSTRACT FROM AUTHOR]

Despite advancements in treatment of infectious diseases, opportunistic pathogens continue to pose a worldwide threat. Identifying a source of infection/inflammation is often challenging which highlights the need of improved diagnostic agents. Using a model of local S. aureus infection, here we evaluated the potential of betamethasone or dexamethasone loaded in poly (lactic acid) nanoparticles and radiolabeled with 99mTc to detect an infection/inflammation site in vivo. A betamethasone and dexamethasone nanoparticles (NPs) with 200 and 220 nm in size, respectively, were created with a 98% 99mTc radiolabeling efficiency. When injected in infected mice, betamethasone NPs presented a higher accumulation in the infected hind paw in comparison with dexamethasone NPs. Our results suggest that this nanosystem may be a valid nanoradiopharmaceutical for the detection of inflammation/infection foci in vivo. [ABSTRACT FROM AUTHOR]

This study aimed to provide an easy method for synthesis of 1-hydroxy-2-(3-pyridyl) ethylidene bisphosphonic acid monosodium (sod. risedronate) with a high yield of 71%. The synthesized risedronate was labeled with technetium-99 m using two different reducing agents (SnCl2.2H2O and NaBH4) where NaBH4 gave stable complex and higher radiochemical yield more than SnCl2.2H2O. The results showed that, the radiochemical purity of 99mTc(NaBH4)-risedronate was 99.2 ± 0.6% and its stability was up to 6 h. Biodistribution study showed high uptake and long retention of 99mTc(NaBH4)-risedronate in bone starting from 15 min (29 ± 2.5% ID/organ) up to 4 h (35.1 ± 3.2 ID/organ) post injection. This research could introduce an easy and effective method for synthesis and labeling of risedrionate and affording a good tracer for bone imaging. [ABSTRACT FROM AUTHOR]

BACKGROUND: Due to aging and unexpected prolonged shutdown of nuclear reactors producing 99Mo for 99Mo/ 99mTc generators it was necessary to explore the alternative methods of technetium-99m production. The first choice were the accelerators. Three years ago IAEA (International Atomic Energy Agency) initiated the Coordinated Research Project “Accelerator-based Alternatives to Non-HEU production of Mo-99 /Tc-99m” aimed at direct production of 99mTc in proton accelerators using the 100Mo(p,2n)99mTc reaction. POLATOM is participating in this enterprise together with the Heavy Ion Laboratory of Warsaw University and the Institute of Nuclear Chemistry and Technology. MATERIAL AND METHODS: 99Mo/99mTc solutions and pure 99mTc used for generators production or milked from ready to use generators were used in experiments. Commercial chromatographic and laboratory-prepared columns were used for separation. The peristaltic pumps were used for solutions delivery onto the columns. Radioactivity of eluted 99Mo and 99mTc was measured using high resolution gamma spectrometry or ionisation chamber in case of high radioactivity. For separation, three different chromatographic methods were used, one based on ion exchange and two on extraction. RESULTS: Synthetic mixtures simulating the real solutions were used. 99mTc is quantitatively bound in the Dowex-1×8 column whereas molybdenum is only slightly retained and totally rinsed with 2M NaOH. 99mTc is eluted with TBAB. The elution yield has been reproducible and amounted to 78%. The AnaLig Tc-02 resin column was used for 99mTc retention. Residual Mo was removed by rinsing with 2M NaOH and 99mTc eluted using small volume of water. The recovery was equal to about 85%. Using C-18 column coated with PEG over 80% of 99mTc was recovered in about 50 mL of water. The reduction of volume was necessary. CONCLUSIONS: The recovery of 99mTc was the highest using AnaLig Tc-02 resin. Time of 99mTc separation is the shortest for AnaLig Tc-02 resin and it is not higher than 100 minutes and it can further be shortened. [ABSTRACT FROM AUTHOR]

Purpose: Based on the authors' previous findings concerning the radiotoxicity of 99mTc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter 123I. To evaluate the relative biological effectiveness (RBE) of both radionuclides, knowledge of the absorbed dose is essential. Thus, the authors present the dose calculations and discuss the results based on different models of the radionuclide distribution. Both different target volumes and the influence of the uptake kinetics were considered. Methods: Rat thyroid PC Cl3 cells in culture were incubated with either 99mTc or 123I or were irradiated using 200 kV x-rays in the presence or absence of perchlorate. The clonogenic cell survival was measured via colony formation. In addition, the intracellular radionuclide uptake was quantified. Single-cell dose calculations were based on Monte Carlo simulations performed using Geant4. Results: Compared with external radiation using x-rays (D37 = 2.6 Gy), the radionuclides 99mTc (D37 = 3.5 Gy), and 123I (D37 = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a37 that was necessary to reduce the surviving fraction (SF) to 0.37 was 22.8 times lower for 99mTc and 12.4 times lower for 123I because of the dose increase caused by intracellular radionuclide accumulation. When the cell nucleus was considered as the target for the dose calculation, the authors found a RBE of 2.18 for 99mTc and RBE = 3.43 for 123I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for 99mTc and RBE = 1.87 for 123I. The dose to the entire cell was chosen as the dose criterion because of the intracellular radionuclide accumulation, which was found to occur solely in the cytoplasm. The calculated number of intracellular decays per cell was (975 ± 109) decays/MBq for 99mTc and (221 ± 82) decays/MBq for 123I. Conclusions: The authors' data indicate that extra-nuclear targets to Auger electrons exist, which is obvious from our dose calculations. When considering the dose to the cell nucleus, the authors found an enhanced RBE for 99mTc and 123I relative to acute x-ray irradiation and pure extracellular irradiation with both radionuclides. Surprisingly, the authors did not find any radionuclide accumulation in the cell nucleus, indicating that there are additional radiosensitive targets besides the DNA. In addition, the authors demonstrated the necessity of cellular dose calculations in radiobiological experiments using unsealed radionuclides and identified the relevant parameters. [ABSTRACT FROM AUTHOR]

Low density polyethylene films were grafted by poly (acrylic acid). The effects of dose, monomer concentration, solvent, inhibitor and thickness of films were investigated. Adsorption capacities of grafted films of Pb2+and Cd2+reached up to 20 and 13 (mg/g), respectively. The complexed grafted films in protection of workers against technetium-99 m radiation dangers were investigated. The effects of grafting percentage, thickness and adsorption capacity of ions on shielding efficiency were studied. The transmission intensity of complexed grafted films decreased gradually until arrived almost 0%. The protection efficiency of complexed grafted films is higher than grafted and virgin films, respectively. [ABSTRACT FROM AUTHOR]