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Due to the favorable physicochemical properties and the biocompatibility, carbon dots (CDs) have gained a great attention as a tumor targeting agent. This study investigates polyethylenimine capped CDs (PEI capped CDs) as a prospective nanocarrier of technetium-99m (99mTc) for tumor targeting. Technetium-labeled CDs could be introduced as a promising candidate for single photon emission tomography (SPECT) imaging. Polyethylenimine capped CDs were prepared by hydrothermal method using hyperbranched PEI and citric acid. For a purpose of comparison, citrate capped CDs were also prepared by microwave irradiation. Both types of CDs were characterized and radiolabeled with 99mTc using sodium borohydride (NaBH4) as a reducing agent. Biodistribution and tumor targeting efficiency of the produced radiolabeled CDs have been studied in Earlich ascites tumor mice model. Citrate capped CDs and PEI capped CDs have been synthesized successfully and characterized. High radiochemical yield of 99mTc-citrate capped CDs 99mTc-PEI capped CDs was obtained (97 ± 0.7 and 90 ± 0.2, respectively). Biodistribution studies of 99mTc-labeled PEI capped CDs have shown a potential tumor uptake (10 ± 0.5% Radioactivity/gram tumor) with high target to non-target ratio (T/NT) around 7 at 1-h post injection. 99mTc-citrate capped CDs have achieved a lower tumor uptake level (3.8 ± 0.3% Radioactivity/gram tumor 1 h post injection). This study introduces PEI capped CDs as a promising nanocarrier of 99mTc for efficient tumor targeting. Technetium-labeled PEI capped CDs could be utilized as a potential SPECT tumor imaging agent. [ABSTRACT FROM AUTHOR]

Early detection of the site of infection non‐invasively with radiolabeled molecules is important for the success of treatment. Technetium‐99m labeled antibiotics have the potential to discriminate between bacterial infection and sterile inflammation. Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. In this study, sultamicillin was labeled with 99mTc according to the stannous chloride method. Quality control studies of radiolabeled sultamicillin were performed by radiochromatographic methods. In vitro binding assays were performed in live and heat‐killed gram‐positive Staphylococcus aureus and gram‐negative Escherichia coli strains. The radiolabeling yield of 99mTc‐sultamicillin was determined as 97.8% ± 3.1% (n = 5). The maximum bacterial uptake of 99mTc‐sultamicillin was 80.7% ± 11.00% at 4 h for living S. aureus and 93.2% ± 4.40% at 2 h for E. coli. Bacterial uptake study results show that sultamicillin has the potential to be a nuclear imaging agent, especially in infections caused by gram‐negative E. coli and gram‐positive S. aureus. [ABSTRACT FROM AUTHOR]

The results of studies performed at the Khlopin Radium Institute in cooperation with other institutions from Russia and other countries, and also published data in the field of chemistry of higher technetium carbonyl compounds are summarized in the context of problems of nuclear medicine. Chemical problems that arise on the way of using higher technetium carbonyls in nuclear medicine and are associated with the synthesis conditions and reactivity of these complexes, and also the ways to solve these problems are analyzed. The major problems are the need for using high pressures in synthesis, the impossibility of direct replacement of halogen in pentacarbonyl halides (products directly obtained from pertechnetate ion) by other monodentate ligands, limited resistance of many higher technetium carbonyls to decarbonylation, and susceptibility of higher technetium carbonyls to nucleophilic reactions (including hydrolysis in alkaline media). The latter problem seems to be the most critical. The scientific outcome of the studies is outlined, and comparison with rhenium analogs is made. The complex [99mTcI(CO)5] shows promise for lung imaging; assumptions concerning the mechanism of its lung uptake are formulated. [ABSTRACT FROM AUTHOR]

Polyvinylpyrrolidone (PVP) is a biopolymer compound that has been widely used in pharmaceutical and medical applications, especially as a tablet binder and solubilizing agents for injections. In this work, PVP was characterized by FTIR to confirm its structure and Dynamic light scattering (DLS) to determine its mean diameter for studying concentration ranges. PVP was radio-labeled with Technetium-99m using SnCl2.2H2O as a reducing agent with an efficiency of (97 ± 0.15) % at the best conditions. The stability 99mTc-PVP complex was measured in serum and saline media in vitro for 24 hours and it was found that the complex had good stability properties for 24 hours. The biological distribution of the 99mTc-PVP complex was studied in normal mice using oral and intravenous injection to discover its accumulation in different mice organs. The results indicated that the rate of the 99mTc-PVP complex in the blood decreased rapidly during the first three hours after injection, and also, it was mainly excreted by the kidneys with negligible uptake in the brain. The results also confirmed that the 99mTc-PVP complex was accumulated with high percentages in the urinary bladder during the 3 hours post-injection. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effect of ursodeoxycholic acid (UDCA) on the biodistribution and excretion of technetium-99m (Tc-99m)-labeled radiopharmaceuticals. Materials and Methods: Tc-99m hydroxy-methylene-diphosphonate (HDP), Tc-99m pertechnetate, and Tc-99m dimercaptosuccinic acid (DMSA) were injected via the tail vein of rats. After 30 min, the control group was administered saline, and the UDCA group was given UDCA orally. Scintigraphy images were acquired after 30 min and 1, 2, 3, and 4 h. Radioactivity and rate of change were compared. Tc-99m mercaptoacetyltriglycine (MAG3) imaging was also performed. Results: In image analysis of Tc-99m HDP, radioactivity of the buttock was lower in the UDCA group at 4 h. Rates of change in the buttock were significantly different at 3 h-30 min and 4 h-30 min, and buttock radioactivity in the UDCA group had decreased more. In analysis of Tc-99m pertechnetate, radioactivity of the buttock was higher in the control group. Rates of change in the thyroid gland and buttock were different at 1 h-30 min, 3 h-30 min, and 4 h-30 min, with radioactivity in the UDCA group decreasing more. In the analysis of Tc-99m DMSA, while the radioactivity of the kidneys in the control group showed little decrease at 1 h-30 min, that in the UDCA group increased. In the analysis of Tc-99m MAG3 images, radioactivity and radioactivity/total body radioactivity (TBA) values for the kidneys were higher in the UDCA group at 2 min. At 5 and 10 min, radioactivity/TBA values for soft tissue in the UDCA group were lower than those in the control group. Conclusion: This study demonstrated that administration of UDCA increases renal excretion and soft tissue clearance of radiopharmaceuticals. This investigation could contribute to the broadening of applications of UDCA. [ABSTRACT FROM AUTHOR]

Serotonergic (5-hydroxytryptamine; 5-HT) receptors play critical roles in neurological and psychological disorders such as schizophrenia, anxiety, depression, and Alzheimer's diseases. Therefore, it is particularly important to develop novel radioligands or modify the existing ones to identify the serotonergic receptors involved in psychiatric disorders. Among the 16 subtypes of serotonergic systems, only technetium-99m based radiopharmaceuticals have been evaluated for serotonin-1A (5-HT 1A), serotonin-2A (5-HT 2A), 5-HT 1A/7 heterodimers and serotonin receptor neurotransmitter (SERT). This review focuses on recent efforts in the design, synthesis and evaluation of 99mTc-radioligands used for single photon emission computerized tomography (SPECT) imaging of serotonergic (5-HT) receptors. Additionally, the discussion will cover aspects such as chemical structure, in vitro / vivo stability, affinity toward serotonin receptors, blood-brain barrier permeation (BBB), and biodistribution study. [Display omitted] • Based on the structure and function of serotonin receptors have been divided into seven families (5-HT 1−7). • Serotonergic receptors have critical roles in neurological and psychological disorders. • Review of design, synthesis, and evaluation of 99mTc-labeled probes synthesized for serotonergic receptor imaging. [ABSTRACT FROM AUTHOR]

[Display omitted] • New C-3 fluoroquinolones derivatives and their [99mTc/Re(CO) 3 ] complexes. • 99mTc-complexes were tested in E. coli bacteria and in E. coli infected mice. • 99mTc-complexes were tested in CT26 tumor cells and in tumor-bearing mice. Fluoroquinolones (FQ) are clinically used antibacterial agents. Antibacterial fluoroquinolone derivatives have been shown to exhibit cytotoxic properties in tumor cells. In this work, C3-carboxy fluoroquinolones derivatives were radiolabeled with the diagnostic radionuclide technetium-99 m and were evaluated as infection- and tumor-targeted agents. First, ciprofloxacin and enrofloxacin were converted to 3-hydrazides and then to the respective pyridine hydrazones (L1 and L2). Secondly, 3-carboxamide of enrofloxacin was converted to dipicolylamine (L3), and picolylaminoacetate (L4) tridentate chelators. The respective rhenium-tricarbonyl complexes of L1-L4 were synthesized and characterized by spectroscopic methods and were used as non-radioactive standards to characterize the analogous 99mTc-radiotracers. The 99mTc-tricarbonyl complexes were synthesized and their lipophilicity and stability were evaluated in vitro. The most stable tracers 99mTcL3, 99mTcL4, were incubated with E. coli cells and CT-26 murine colon adenocarcinoma cells to assess their cellular uptake. Also, the 99mTc-tracers were injected in mice, infected with E. coli, as well as in mice, bearing CT-26 tumors. [ABSTRACT FROM AUTHOR]

The aim of this study was to synthesis an imaging agent for tumor targeting. New recombinant insulin analogue was successfully produced from E. coli by recombinant DNA technique, and was well labeled with Technetium-99m with a high radiochemical yield of 93.3 ± 2.1 %. Moreover, it showed good in-vitro stability in both saline and human serum. Preclinical evaluation of Technetium-99m [99mTc] Tc-insulin in solid tumor-bearing mice showed high accumulation in tumor tissues. The T/NT (target to non-target ratio) was of 5.4, after 60 min. of post injection (p.i). The direct intra-tumoral (I.T) injection of [99mTc] Tc-insulin showed good retention in tumor tissues with a ratio more than 50 % after 15 min. As a result of the promising bio-distribution studies; the newly recombinant insulin showed good uptake in tumor site, which assured high concentration of insulin receptor on tumor cell surface, accompanied with high cell density of tumor cells as well. This work affords a potential radiocarrier that could be used as a good tumor marker and imaging probe via SPECT (Single Photon Emission Computed Tomography) technique, after further preclinical studies.

As radiation science and technology advances, nuclear medicine applications are increasing worldwide which necessitate the understanding of biological implications of such practices. Ionizing radiation has been shown to cause degraded matrix and reduced proteoglycan synthesis in cartilage, and the late consequences of which may include degenerative arthritis or arthropathy. Although degenerative effects of the ionizing radiation on cartilage tissue have been demonstrated, the effects on the mechanical properties of articular cartilage are largely unknown. The radiopharmaceuticals, technetium-99m and technetium-99m sestamibi, were utilized on bovine articular cartilage to investigate these effects. We used two different mechanical tests to determine the mechanical properties of articular cartilage. Dynamic and static mechanical tests were applied to calculate compressive modulus for articular cartilage. We observed clearly higher control modulus values than that of experimental groups which account for lesser stiffness in the exposed cartilage. In conclusion, compressive moduli of bovine articular cartilage were found to decrease after radiopharmaceutical exposure, after both instantaneous and equilibrium mechanical experiments.

Leanne De Silva,1 Ju-Yen Fu,2 Thet Thet Htar,1 Saravanan Muniyandy,3 Azahari Kasbollah,4 Wan Hamirul Bahrin Wan Kamal,4 Lay-Hong Chuah1,5 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia; 2Nutrition Unit, Malaysian Palm Oil Board, Bandar Baru Bangi, Selangor, Malaysia; 3Department of Pharmacy, Fatima College of Health Sciences, Al Ain, United Arab Emirates; 4Medical Technology Division, Malaysian Nuclear Agency, Bangi, Selangor, Malaysia; 5Advanced Engineering Platform, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia 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 (99mTc) will allow for the tracking of the nanocarrier noninvasively via nuclear imaging. The purpose of this study was to formulate, characterize, and optimize 99mTc-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 1H and 13C nuclear magnetic resonance spectroscopy). Niosomes were radiolabeled by surface chelation with reduced 99mTc. Parameters affecting the radiolabeling efficiency such as concentration of stannous chloride (SnCl2·H2O), 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 SnCl2·H2O 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. 99mTc-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 99mTc. The formulated 99mTc-labeled niosomes possessed high radiolabeling efficacy, good stability in vitro, and show good promise for potential use in nuclear imaging in the future. Keywords: nanotechnology, nanocarriers, radiolabeling, drug delivery, formulation, nuclear imaging

The purpose of this study was to determine the optimum conditions for labeling genistein compounds with technetium-99m (99mTc) radionuclides and the percentage of purity obtained in accordance with the requirements of the United State Pharmacopeia. The method used is optimization of several parameters including pH, SnCl2.2H2O as reducing agents, genistein concentration, and incubation time. The results showed that the optimum conditions for labeling 99mTc-Genistein were obtained under conditions of pH 8, the amount of SnCl2.2H2O reducing agents was 30 μg, 0.5 mg genistein, and in 10 min. The optimization of this condition resulted in radiochemical purity in the labeling of 99mTc-Genistein compounds at 95.43% ± 0.85%. The radiochemical purity of the labeling of 99mTc-Genistein compounds has met the requirements of the United State Pharmacopeia as a compound marked for diagnosis of more than 90%.

The combination of two imaging modalities in a single agent has received increasing attention during the last few years, since its synergistic action guarantees both accurate and timely diagnosis. For this reason, dual-modality contrast agents (DMCAs), such as radiolabeled iron oxide (namely Fe3O4) nanoparticles, constitute a powerful tool in diagnostic applications. In this respect, here we focus on the synthesis of a potential single photon emission computed tomography/magnetic resonance imaging (SPECT/MRI) DMCA, which consists of Fe3O4 nanoparticles, surface functionalized with 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD) and radiolabeled with 99mTc, [99mTc]Tc-DPD-Fe3O4. The in vitro stability results showed that this DMCA is highly stable after 24 h of incubation in phosphate buffer saline (~92.3% intact), while it is adequately stable after 24 h of incubation with human serum (~67.3% intact). Subsequently, [99mTc]Tc-DPD-Fe3O4 DMCA was evaluated in vivo in mice models through standard biodistribution studies, MR imaging and gamma-camera imaging. All techniques provided consistent results, clearly evidencing noticeable liver uptake. Our work documents that [99mTc]Tc-DPD-Fe3O4 has all the necessary characteristics to be a potential DMCA.

BackgroundThis study aimed to evaluate the clinical value of indocyanine green sentinel lymph node (SLN) mapping in patients with vulvar cancer. The conventional procedure of SLN mapping in vulvar cancer includes peritumoral injection of technetium-99m nanocolloid before surgery and intraoperative injection of a blue dye. However, these techniques harbor some limitations. Near-infrared fluorescence imaging with indocyanine green has gained popularity in SLN mapping in different types of cancer.MethodsWe analyzed retrospectively vulvar cancer patients at our institution between 2013 and 2020 undergoing indocyanine green SLN mapping by applying video telescope operating microscope system technology.Results64 groins of 34 patients were analyzed. In 53 groins we used technetium-99m nanocolloid, in four patent blue, and in five both techniques, additionally to indocyanine green for SLN detection. In total, 120 SLNs were identified and removed. The SLN detection rate of indocyanine green was comparable to technetium-99m nanocolloid (p=.143) and higher than patent blue (p=.003). The best results were achieved using a combination of ICG and technetium-99m nanocolloid (detection rate of 96.9%). SLN detection rates of indocyanine green were significantly higher in patients with positive lymph nodes (p=.035) and lymphatic space invasion (p=.004) compared to technetium-99m nanocolloid.ConclusionIndocyanine green SLN mapping in vulvar cancer is feasible and safe, with reasonable detection rates. Due to its easy application and few side effects, it offers a sound alternative to the conventional SLN mapping techniques in vulvar cancer. In patients with lymph node metastasis, indocyanine green even outperformed technetium-99m nanocolloid in terms of detection rate.

Background: This study aimed to evaluate the clinical value of indocyanine green sentinel lymph node (SLN) mapping in patients with vulvar cancer. The conventional procedure of SLN mapping in vulvar cancer includes peritumoral injection of technetium-99m nanocolloid before surgery and intraoperative injection of a blue dye. However, these techniques harbor some limitations. Near-infrared fluorescence imaging with indocyanine green has gained popularity in SLN mapping in different types of cancer. Methods: We analyzed retrospectively vulvar cancer patients at our institution between 2013 and 2020 undergoing indocyanine green SLN mapping by applying video telescope operating microscope system technology. Results: 64 groins of 34 patients were analyzed. In 53 groins we used technetium-99m nanocolloid, in four patent blue, and in five both techniques, additionally to indocyanine green for SLN detection. In total, 120 SLNs were identified and removed. The SLN detection rate of indocyanine green was comparable to technetium-99m nanocolloid (p=.143) and higher than patent blue (p=.003). The best results were achieved using a combination of ICG and technetium-99m nanocolloid (detection rate of 96.9%). SLN detection rates of indocyanine green were significantly higher in patients with positive lymph nodes (p=.035) and lymphatic space invasion (p=.004) compared to technetium-99m nanocolloid. Conclusion: Indocyanine green SLN mapping in vulvar cancer is feasible and safe, with reasonable detection rates. Due to its easy application and few side effects, it offers a sound alternative to the conventional SLN mapping techniques in vulvar cancer. In patients with lymph node metastasis, indocyanine green even outperformed technetium-99m nanocolloid in terms of detection rate. [ABSTRACT FROM AUTHOR]

With the long-term goal of developing a diagnostic (99mTc) and therapeutic (186Re) agent pair for targeting somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs), we developed novel metal-cyclized peptides through direct labeling of the potent SSTR2 antagonist Ac-4-NO 2 -Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH 2 (1) with Re (in Re- 1), 99mTc (in [99mTc]Tc- 1) and 186Re (in [186Re]Re- 1). Re- 1 was characterized by LC-ESI-MS and HR-ESI-MS and was tested for receptor affinity in SSTR-expressing cells (AR42J). Radiolabeling of the peptide was achieved via ligand exchange from 99mTc-labeled glucoheptonate or [186Re]ReOCl 3 (PPh 3) 2 , yielding [99mTc]Tc- 1 or [186Re]Re- 1 , respectively. In vitro stability of [99mTc]Tc- 1 /[186Re]Re- 1 in PBS (10 mM) at pH 7.4 and 37 °C was determined by HPLC analysis. Moreover, [99mTc]Tc- 1 stability was tested in cysteine (1 mM) and rat serum under the same conditions. Re- 1 consisted of two isomers, confirmed by LC-ESI-MS, with good SSTR2 affinity (IC 50 = 43 ± 6 nM). Optimization of the 99mTc labeling through varying reaction parameters such as pH, reaction time, and Sn2+ and ligand concentrations resulted in high radiochemical yield (RCY ≥92%). Similarly, [186Re]Re- 1 was prepared in reasonable RCY (≥50%). Both 99mTc/186Re-tracers consisted of two product isomers as identified by HPLC co-injection with Re- 1. While [99mTc]Tc- 1 was sufficiently stable in vitro (≥71% intact through 4 h in PBS, cysteine and rat serum), [186Re]Re- 1 exhibited more moderate in vitro stability (58% intact after 1 h in PBS). Novel 99mTc/186 Re -cyclized SSTR2 antagonist peptides were synthesized and characterized using the Re-cyclized analogue as a reference. Due to the nanomolar SSTR2 affinity of Re- 1 and good in vitro stability of [99mTc]Tc- 1 , the latter shows early promise for development as a radiodiagnostic agent for SSTR-expressing NETs. The 99mTc-cyclized complex showed promising in vitro properties, and future in vivo studies will determine the potential for translating such a design into the human clinic. [Display omitted] [ABSTRACT FROM AUTHOR]

Tumor microenvironment fibroblasts overexpress the fibroblast activation protein (FAP). We recently reported the preclinical evaluation of [99mTc]Tc-iFAP as a new SPECT radioligand capable of detecting FAP. This research aimed to evaluate the kinetic and dosimetric profile of [99mTc]Tc-iFAP in healthy volunteers, and to assess the radioligand uptake by different solid tumors in three cancer patients. [99mTc]Tc-iFAP was obtained from lyophilized formulations prepared under GMP conditions with >98% radiochemical purity. Whole-body scans of six healthy subjects were obtained at 0.5, 2, 4, and 24 h after [99mTc]Tc-iFAP (740 MBq) administration. A 2D-planar/3D-SPECT hybrid activity quantitation method was used to fit the biokinetic models of the source organs (volume of interest: VOI) as exponential functions (A(t)VOI). The total nuclear transformations (N) that occurred in the source organs were calculated from the mathematical integration (0,∞) of A(t)VOI. The OLINDA code was used to estimate the radiation doses. Three treatment-naive patients (breast, lung, and cervical cancer) with a prior [18F]FDG PET/CT scan underwent whole-body, chest, and abdominal SPECT/CT scanning after [99mTc]Tc-iFAP (740 MBq) administration. Both imaging methods were compared visually and quantitatively. Oncological diagnoses were performed histopathologically. The results showed favorable [99mTc]Tc-iFAP biodistribution and kinetics due to rapid blood activity removal (t1/2α = 2.22 min and t1/2β = 90 min) and mainly renal clearance. The mean radiation equivalent doses were 5.2 ± 0.8 mSv for the kidney and 1.7 ± 0.3 mSv for the liver after administration of 740 MBq. The effective dose was 2.3 ± 0.4 mSv/740 MBq. [99mTc]Tc-iFAP demonstrated high and reliable uptake in the primary tumor lesions and lymph node metastases in patients with breast, cervical, and lung cancer, which correlated with that detected by [18F]FDG PET/CT. The tumor microenvironment molecular imaging from cancer patients obtained in this research validates the performance of additional clinical studies to determine the utility of [99mTc]Tc-iFAP in the diagnosis and prognosis of different types of solid tumors.

Recently, prostate-specific membrane antigen (PSMA) has gained momentum in tumor nuclear molecular imaging as an excellent target for both the diagnosis and therapy of prostate cancer. Since 2008, after years of preclinical research efforts, a plentitude of radiolabeled compounds mainly based on low molecular weight PSMA inhibitors (PSMA-i) have been described for imaging and theranostic applications, and some of them have been transferred to the clinic. Most of these compounds include radiometals (e.g., 68Ga, 64Cu, 177Lu) for positron emission tomography (PET) imaging or endoradiotherapy. Nowadays, although the development of new PET tracers has caused a significant drop in single-photon emission tomography (SPECT) research programs and the development of new technetium-99m (99mTc) tracers is rare, this radionuclide remains the best atom for SPECT imaging owing to its ideal physical decay properties, convenient availability, and rich and versatile coordination chemistry. Indeed, 99mTc still plays a relevant role in diagnostic nuclear medicine, as the number of clinical examinations based on 99mTc outscores that of PET agents and 99mTc-PSMA SPECT/CT may be a cost-effective alternative for 68Ga-PSMA PET/CT. This review aims to give an overview of the specific features of the developed [99mTc]Tc-tagged PSMA agents with particular attention to [99mTc]Tc-PSMA-i. The chemical and pharmacological properties of the latter will be compared and discussed, highlighting the pros and cons with respect to [68Ga]Ga-PSMA11.

Purpose: The goal of this work was to develop hydrophilic gastrin-releasing peptide receptor (GRPR)-targeting complexes of the general formula fac-[M(CO)3(L)]+ [M = natRe, 99mTc, 186Re; L: NOTA for 1, NODAGA for 2] conjugated to a powerful GRPR peptide antagonist (DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) via a 6-aminohexanoic acid linker. Procedures: Metallated-peptides were prepared employing the [M(OH2)3(CO)3]+ [M = Re, 99mTc, 186Re] precursors. Re-1/2 complexes were characterized with HR-MS. IC50 studies were performed for peptides 1/2 and their respective Re-1/2 complexes in a binding assay utilizing GRPR-expressing human PC-3 prostate cancer cells and [125I]I-Tyr4-BBN as the competing ligand. The 99mTc/186Re-complexes were identified by HPLC co-injection with their Re-analogues. All tracers were challenged in vitro at 37 °C against cysteine/histidine (phosphate-buffered saline 10 mM, pH 7.4) and rat serum. Biodistribution and micro-SPECT/CT imaging of [99mTc]Tc-1/2 and [186Re]Re-2 were performed in PC-3 tumor-bearing ICR SCID mice. Results: High in vitro receptor affinity (IC50 2–3 nM) was demonstrated for all compounds. The 99mTc/186Re-tracers were found to be hydrophilic (log D7.4 ≤ − 1.35) and highly stable. Biodistribution in PC-3 xenografted mice revealed good tumor uptake (%ID/g at 1 h: 4.3 ± 0.7 for [99mTc]Tc-1, 8.3 ± 0.9 for [99mTc]Tc-2 and 4.2 ± 0.8 for [186Re]Re-2) with moderate retention over 24 h. Rapid renal clearance was observed for [99mTc]Tc-2 and [186Re]Re-2 (> 84 % at 4 h), indicating favorable pharmacokinetics. Micro-SPECT/CT images for the 99mTc-tracers clearly visualized PC-3 tumors in agreement with the biodistribution data and with superior imaging properties found for [99mTc]Tc-2. Conclusions: [99mTc]Tc-2 shows promise for further development as a GRPR-imaging agent. [186Re]Re-2 demonstrated very similar in vivo behavior to [99mTc]Tc-2, and further studies are therefore justified to explore the theranostic potential of our approach for targeting of GRPR-positive cancers. [ABSTRACT FROM AUTHOR]

We studied an original radiolabeled complex of antimicrobial peptides UBI29-41 and UBI18-35, ubiquicidin derivatives, for distinguishing between bacterial and aseptic inflammation. For radiolabeling of the peptides with technetium-99m, a bifunctional chelating agent succinimide-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used. The obtained complexes 99mТс-DPAH-UBI29-41 and 99mТс-DPAH-UBI18-35 had radiolabeling yield >80% and radiochemical purity >96%. Accumulation of the complexes in the focus of bacterial inflammation in bone structures and the absence of this complex in the site of aseptic inflammation was confirmed in a rat model of traumatic osteomyelitis by single-photon emission computed tomography. [ABSTRACT FROM AUTHOR]

Aim: Review of daily used 99Mo/99mTc generator and 99mTc radionuclide itself. Introduction: Technetium-99m is one of the most widely used diagnostic radionuclides in nuclear medicine. It is daily obtained from 99Mo/99mTc radionuclide generator at nuclear medicine departments. It is mostly used for the preparation of a wide range of radiopharmaceuticals. Almost 90 % of all SPECT examinations are performed by 99mTc-labeled radiopharmaceuticals. Issue description: However, there are many processes behind these everyday operations that are not visible at first glance - from the various options of parent radionuclide preparation, through the individual radionuclide generators' design, to the 99mTc elution itself. In this article, the attention is also focused on the important chemical and physical properties of the radionuclide – 99mTc, which makes it so widely used. Despite these processes and properties, it is important not to forget the quality control, which must be carried out before use, whether as regards the eluate or the prepared radiopharmaceutical. Technetium-99m is commonly used not only to cancer diagnoses. It is also used in cardiology, nephrology or neurology. This article provides an overview of the most commonly used radiopharmaceuticals with their possible usage. Conclusion: The importance of 99Mo/99mTc generator is evident and most examinations in nuclear medicine are based on it. For this reason, it is important to occasionally review the principles of production and preparation of given radionuclides and moreover, the characteristics that make it possible to prepare given radiopharmaceuticals quite easily. However, it is necessary also to mention the pitfalls and problems that these processes bring with them. [ABSTRACT FROM AUTHOR]

The aim of current study is to develop new nanostructured lipid carrier systems (NLCSs) containing imatinib mesylate (IMT) and evaluate their targeting efficiency on NIH-3T3 as fibroblast cells and CRL-1739 as gastric adenocarcinoma cells with radiolabeled formulations. Three formulations (F1-IMT, F2-IMT and F3-IMT) were prepared and radiolabeled with 1 mCi/0.1 mL of [99mTc]Tc. The effect of reducing and antioxidant agents on radiolabeling process was evaluated and radiochemical purity of formulations was performed by radio thin-layer radiochromatography (RTLC). The results demonstrated that the radiochemical purity was found to be above 90% for [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT, while radiochemical purity of [99mTc]Tc-F3-IMT was found to be 85.61 ± 2.24%. Also, [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT have better stability in cell medium and saline than [99mTc]Tc-F3-IMT. Targeting efficiency of [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT comparatively evaluated by cell binding studies with [99mTc]NaTcO4 on NIH-3T3 and CRL-1739 cells. The cell binding capacity and targeting/non-targeting cell uptake ratio of these two formulations was found to be higher than [99mTc]NaTcO4 in CRL-1739. It is thought that the knowledge achieved in this study would contribute to using [99mTc]Tc-F1-IMT and [99mTc]Tc F2-IMT as an diagnosis and treatment agents. [ABSTRACT FROM AUTHOR]

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [99mTc]Tc-Sestamibi, [99mTc]Tc-Tetrofosmin, and [99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [99mTc]Tc-Sestamibi and [99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in 99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.

Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. 68Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl2 for labeling with 99mTc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand (Ki = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, 1H–NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The 99mTc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the 99mTc-iFAP.

A system dynamics model for simulating radionuclide generators inventory management decisions is presented in this research report. The radiopharmaceutical is generated gradually from another radioactive element, so called mother element in the radionuclide generators, and after each extraction of the produced radioactive material, so called elution, the radiopharmaceutical is produced in the proportion of the residue from the mother element. Based on the remained mother element, production time dependence, mutual interaction of variables, nonlinear distribution function, and reproduction, lead to the incremental complexity of the mathematical model and cause the model making affair harder in common place operation research methods. In the proposed model appeared in this report, the above-mentioned factors are modeled and due to the nature of system dynamics models' development and the possibility of developing the boundary of the model, the feasibility of utilizing the model, as a basic one, in more complex modeling affairs is presented. The model behavior re-production tests and the system dynamics' extreme conditions, illustrate the validity of the proposed model. Ultimately, in this paper, several scenarios for the productivity raise are illustrated and twenty five percent improvement has been shown compared to the conventional models.

The purpose of the study was to review available literature on the efficacy of radiopharmaceuticals based on glucose derivatives labeled with radioactive isotopes for detection of various cancers. Material and methods. A systematic literature review was performed using the Scopus, Web of Science, MedLine, Cochrane Library, EMBASE, and Global Health databases from 2000 to 2016. Out of 900 papers in the field of nuclear medicine, 58 were included into the review. Results. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) has been approved to be a powerful imaging tool for the detection of various cancers as well as for the assessment of tumor extent and therapy response. There is a continuous search for new more specific and effective radiopharmaceuticals for visualization of tumor tissue. Many studies are devoted to the development of radiopharmaceuticals based on technetium-99m labeled glucose derivatives for tumor visualization. Russian researches have made a significant progress in the development of imaging agents for single-photon emission computed tomography. Conclusion. Despite the widespread use of positron emission tomography technologies, which have proved to be effective, the specialists still have a great interest in radiopharmaceuticals based on technetium-99m. The literature review suggests that the emergence of a diagnostic radiopharmaceutical based on technetium-99m labeled glucose derivative will help to improve the availability of nuclear medicine methods and their effectiveness.

Haloperidol (Hal) is one of the widely used antipsychotic drugs. When orally administered, it suffers from low bioavailability due to hepatic first pass metabolism. This study aimed at developing Hal-loaded penetration enhancer-containing spanlastics (PECSs) to increase transdermal permeation of Hal with sustained release. PECSs were successfully prepared using ethanol injection method showing reasonable values of percentage entrapment efficiency, particle size, polydispersity index and zeta potential. The statistical analysis of the ex vivo permeation parameters led to the choice of F1L – made of Span® 60 and Tween® 80 at the weight ratio of 4:1 along with 1% w/v Labrasol® – as the selected formula (SF). SF was formulated into a hydrogel by using 2.5% w/v of HPMC K4M. The hydrogel exhibited good in vitro characteristics. Also, it retained its physical and chemical stability for one month in the refrigerator. The radiolabeling of SF showed a maximum yield by mixing of 100 µl of diluted formula with 50 µl saline having 200 MBq of 99mTc and containing 13.6 mg of reducing agent (NaBH4) and volume completed to 300 µl by saline at pH 10 for 10 min as reaction time. The biodistribution study showed that the transdermal 99mTc-SF hydrogel exhibited a more sustained release pattern and longer circulation duration with pulsatile behavior in the blood and higher brain levels than the oral 99mTc-SF dispersion. So, transdermal hydrogel of SF may be considered a promising sustained release formula for Hal maintenance therapy with reduced dose size and less frequent administration than oral formula.

The aim of this study was to prepare radiolabeled peptide‐based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium‐99m, two analogs were designed and compared: an antitumor‐antibody‐derived peptide based on the EPPT sequence and a novel retro‐inverso peptidomimetic derivative D(TPPE) structurally modified by replacing the L‐amino acids with D‐amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC‐conjugated peptides were labeled with 99mTc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for 99mTc‐HYNIC‐EPPT and 99mTc‐HYNIC‐D(TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of 99mTc‐HYNIC‐D(TPPE) was more favorable than that of 99mTc‐HYNIC‐EPPT as a result of better tumor‐to‐non‐target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with 99mTc‐HYNIC‐D(TPPE) in comparison with 99mTc‐HYNIC‐EPPT. The results showed the retro‐inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT‐29 tumors than the parent peptide. [ABSTRACT FROM AUTHOR]

Thidiazuron (TDZ) was reported to possess anti-cancer activity against Human cervical carcinoma cell line, so that this study has been conducted for the radiolabeling of TDZ with Technetium-99m. The conditions of the radiolabeling process were optimized and a high radiochemical yield of 93.1 ± 0.35% has been obtained. Molecular docking study illustrated that [99mTc]technetium bisthiadiazuron (99mTc-TDZ) complex has the ability to bind with Caspase-3 protein that over expressed in cancers. Its in-vivo biodistribution on solid tumor bearing mice showed comparatively high T/NT ratio of 6.87 ± 0.14 at 60 min post injection. These promising characteristics make our new designed labeled conjugate a very suitable candidate for molecular imaging of solid tumors, particularly in the cervix. [ABSTRACT FROM AUTHOR]

This study aims to estimate the absorbed doses and biological parameters in the critical organs of patients during bone scan scintigraphy, using SPECT data based on technetium 99m-methyl diphosphonate ("mTc-MDP) in nuclear medicine (NM) procedures. Tc uptake of different critical organs (ROIs) such as kidneys and bladder were calculated at different times (0.2 h, 1 h, 1.45 h, and 3 h) after the administration of mean activityA0 equal to 11.53 mCi. The absorbed dose, biological half-life (T1/2), and residence time (t) were computed using Medical Internal Radiation Dosimetry (MIRD) Report 13 of biokinetic model. The data were analyzed using a computational toolkit called (IntDosCalc) developed under Matlab code. The results of the present study showed that the value of the absorbed dose for critical organs such as the kidney and bladder were 0.007 and 0.393 mGy per unit of administrated activity, respectively. The cumulated activity, residence time, effective half-life and biological half-life were discussed in detail. [ABSTRACT FROM AUTHOR]

A novel sulphonamide derivative (EPBS) was prepared at high yield and characterized by 1H NMR and infrared radiation spectroscopy. Its cytotoxic activity was examined in breast carcinoma (MCF-7) cells at a dose of 25 μg/mL. Approximately 68 percent effective inhibition has been achieved. Furthermore, the synthesized ligand was directly radiolabeled with technetium-99m using sodium borohydride. High radiochemical purities (95.5%) were determined using radio-paper chromatography and electrophoresis. Its in vivo evaluation in tumor bearing mice demonstrated a high tumor uptake of the 99mTc-EPBS complex at 30 min post injection (6.74%) and tumor/muscle (T/NT) ratio equal to 5.04 ± 0.05. In conclusion, 99mTc-EPBS agent showed favorable characteristics for the radio-diagnosis of solid tumors. [ABSTRACT FROM AUTHOR]

Targeted drug delivery system can reduce the side effects of high drug concentration by improving drug pharmacokinetics at lower doses. Citrate-gold nanoparticles (AuNPs) as a drug delivery system were synthesized via green nanotechnology technique to be used as a new imaging platform for tumor targeting. Citrate-AuNPs were synthesized with core size of 10 nm. Citrate-AuNPs were labeled with technetium-99m (99mTc) with radiochemical yield of 95.20 ± 2.70% with good in-vitro stability in both saline and human serum and well in-vivo studied in both normal and solid tumor bearing mice. The in-vivo biodistribution study of [99mTc]Tc-citrate-AuNPs in solid tumor bearing mice (as preliminary study) showed a high accumulation in tumor site with tumor/muscle of 4.35 ± 0.22 after 30 min post injection. The direct intratumoral (I.T) injection of [99mTc]Tc-citrate-AuNPs showed that this complex was retained in the tumor up to 77.86 ± 1.90 % at 5 min and still around 50.00 ± 1.42 % after 30 min post injection (p.i.). The newly presented nano-platform could be presented as a new potential radiopharmaceutical tumor imaging probe. [ABSTRACT FROM AUTHOR]

Purpose: Olanzapine (OLZ) is an atypical antipsychotic agent that is characterized by low brain porousness. The present work aimed to develop radiolabeled olanzapine (OLZ) without colloidal impurities and evaluate its biodistribution following intravenous (I.V.) and intranasal (I.N.) administration as a potential agent for brain diagnosis. Materials and methods: OLZ was radiolabeled with technetium-99m by using sodium dithionite as the reducing agent. Biodistribution of 99mTc-OLZ complex in mice following I.V. and I.N. administrations was examined. Furthermore, a molecular docking study was performed. Results: Sodium dithionite labeling procedure resulted in highest radiochemical yield (96.30 ± 0.09%) and in vitro stability in serum up to 8 h. Biodistribution study of 99mTc-OLZ complex showed high brain uptake following I.N. (6.2 ± 0.12% ID/g) and I.V. (5.5 ± 0.09% ID/g) at 0.5 and 1 h post administration (P.I.), respectively. Docking into two brain targets predicts higher affinity of 99mTc-OLZ than free OLZ. Additionally, docking to P-glycoproteins shows less affinity for the radiolabelled OLZ and hence it is expected to be associated with better brain exposure than free OLZ. Conclusion: These chemical and preliminary biological merits strongly suggest that the 99mTc-OLZ complex with new reducing agent could be used as a potential diagnostic agent for brain. [ABSTRACT FROM AUTHOR]

Background: Recently, a new family of 99mTc(I)-tricarbonyl complexes bearing an acridine orange (AO) DNA targeting unit and different linkers between the Auger emitter (99mTc) and the AO moiety was evaluated for Auger therapy. Among them, 99mTc-C3 places the corresponding radionuclide at a shortest distance to DNA and produces important double strand breaks (DSB) yields in plasmid DNA providing the first evidence that 99mTc can efficiently induce DNA damage when well positioned to the double helix. Here in, we have extended the studies to human prostate cancer PC3 cells using the 99mTc-C3 and 99mTc-C5 complexes, aiming to assess how the distance to DNA influences the radiation-induced biological effects in this tumoral cell line, namely, in which concerns early and late damage effects. Results: Our results highlight the limited biological effectiveness of Auger electrons, as short path length radiation, with increasing distances to DNA. The evaluation of the radiation-induced biological effects was complemented with a comparative microdosimetric study based on intracellular dose values. The comparative study, between MIRD and Monte Carlo (MC) methods used to assess the cellular doses, revealed that efforts should be made in order to standardize the bioeffects modeling for DNA-incorporated Auger electron emitters. Conclusions: 99mTc might not be the ideal radionuclide for Auger therapy but can be useful to validate the design of new classes of Auger-electron emitting radioconjugates. In this context, our results highlight the crucial importance of the distance of Auger electron emitters to the target DNA and encourage the development of strategies for the fine tuning of the distance to DNA for other medical radionuclides (e.g., 111In or 161Tb) in order to enhance their radiotherapeutic effects within the Auger therapy of cancer. [ABSTRACT FROM AUTHOR]

Radionuclide whole‑body bone scan is a useful investigation of choice to detect the skeletal metastases in prostate cancer. It is indicated in patients having elevated serum prostate‑specific antigen (Sr. PSA) or patients with bone pain. Elevated Sr. PSA levels have high predictive value for skeletal metastases; however, there is no consensus regarding cut-off value of Sr. PSA above which bone scan is indicated. This study was performed to find out the accuracy of Sr. PSA test and to know the optimal cut-off value of Sr. PSA with high sensitivity and specificity in the prediction of skeletal metastases on bone scan in prostate cancer patients. A retrospective analysis of medical records of 307 prostate cancer patients referred to the department of nuclear medicine for bone scan between June 2009 and June 2014 was done. Of 307 patients, 15 cases were excluded due to nonavailability of Sr. PSA. Bone scan was performed 3 h after administration of 20 mCi Tc‑99m methylene diphosphonate intravenously. Whole‑body sweep imaging was performed and spot views were taken wherever required. Of 292 cases, 174 (59.58%) patients had positive bone scan for metastases and 118 (40.41%) patients had negative bone scan for metastases. Maximum and minimum Sr. PSA levels in positive and negative bone scan patients were 1260 and 0.02 ng/ml and 198.34 ng/ml and 0.01 ng/ml, respectively. On comparison of the mean Sr. PSA levels between positive and negative groups, we found significant Sr. PSA levels (P < 0.05). We used receiver operating characteristic (ROC) curve analyses to find out the accuracy of Sr. PSA test and to know the optimal cut-off value of Sr. PSA with maximum sensitivity and specificity in the prediction of skeletal metastases on bone scan. Area under ROC curve was 0.878 (87%). This indicates that the accuracy of Sr. PSA test in the prediction of skeletal metastases on bone scan was good. The optimal cut-off value of Sr. PSA in the prediction of positive bone scan for skeletal metastases in the management of prostate cancer was 29.16 ng/ml, with sensitivity and specificity of 89.0% and 74.6%, respectively. In this study, we conclude that the accuracy of Sr. PSA test in the prediction of skeletal metastases is good. ROC‑derived optimal cut-off value of Sr. PSA for positive skeletal metastases on bone scan is >29.16 ng/ml; thus, the chances of getting positive bone scan for skeletal metastasis are less in prostate cancer patients with Sr. PSA <29.16 ng/ml. ROC‑derived sensitivity and specificity of different possible cut-off points of Sr. PSA help reduce the false positive results and increase the diagnostic accuracy of bone scan in the detection of skeletal metastases in prostate cancer patients. [ABSTRACT FROM AUTHOR]

In the current study, ibuprofen (ibu) which is a non-steroidal anti-inflammatory drug (NSAID) was radiolabeled with 99mTc using two different methods: stannous chloride method (direct route) and technetium-99m tricarbonyl [99mTc(CO)3]+ route. Thus, it's aimed to investigate the radiolabeling potential of ibu for inflammation detection and to monitor if there is any difference in in vivo distribution depending on the radiolabeling route. Quality control studies of both radiolabeled ibu were performed by radiochromatographic methods (Thin Layer Liquid Radio Chromatography and High Performance Liquid Radio Chromatography). Radiolabeling yields of 99mTc-ibu and 99mTc(CO)3-ibu were determined as 99.05 ± 0.83% and 91.79 ± 3.30% (n = 5), respectively. Experimental lipophilicities of both radiolabeled ibu were determined. The biological behavior of both radiolabeled ibu was investigated in healthy Albino Wistar male rats by in vivo biodistribution studies. It was seen that both radiolabeled ibuprofen showed renal excretion while organ uptakes of 99mTc-ibu and 99mTc(CO)3-ibu differ against time. [ABSTRACT FROM AUTHOR]

The target of this study is the synthesis of a new diester derivative and radiolabeling with one of the most effective diagnostic radioisotopes to be investigated as a novel targeting radiotracer for tumor imaging. 10‐[2‐(9‐Carboxynonanoyloxy)propoxy]‐10‐oxodecanoic acid was synthesized in excellent yield and characterized by Fourier‐transform infrared spectroscopy, mass, 1H‐NMR, and 13C‐NMR spectra. The diester was technetium‐99m (99mTc) radiolabeled by direct technique using sodium dithionite as a reducing agent. The labeling parameters such as diester amount, reducing agent amount, pH of the medium, and reaction time were optimized. High radiochemical yield of 95.10 ± 0.41% and in vitro stability in serum up to 12 h have been obtained on complexation of the synthesized diester with Tc‐99m. Evaluation of the diester anticancer activity against breast cancer cell line (MCF‐7) showed high percent of inhibition about 61.5% at 100 μg/ml. The rhenium complex of the diester was synthesized and characterized by liquid chromatography–mass spectrometry (ESI) and elemental analysis depending on the strong chemical resemblance between Tc and Re. Biodistribution studies of 99mTc‐diester complex showed high target to nontarget ratio (T/NT) equals 6.24 ± 0.09 in tumor‐bearing mice at 30‐min postinjection, suggesting this complex could be used as hopeful solid tumor‐imaging agent. [ABSTRACT FROM AUTHOR]

Nanodiamonds (NDs) were investigated as potential carriers of 99mTc, which is widely used for the diagnosis of diseases in nuclear medicine. The sorption of 99Tc(VII), 99mTc(VII), and 99mTc(IV) by commercial NDs and their reduced, aminated, and oxidized forms was studied. The physicochemical parameters of the Langmuir and Freundlich isotherms for the sorption of 99Tc(VII) by the used ND samples were determined. The Sn(II): Tc(VII) ratio for the quantitative reduction of Tc to the oxidation state IV was optimized. It was shown that the initial (commercial) and oxidized NDs are promising carriers of 99mTc(IV) for nuclear medicine. [ABSTRACT FROM AUTHOR]

Background: We studied the impact of technetium-99m (99mTc) in the thallium-201 (201Tl) energy window (70 keV) to determine if CZT cardiac cameras allow us to perform simultaneous dual-isotope acquisition for myocardial perfusion imaging.Methods: We included 117 consecutive patients. We injected 0.7 MBq/kg of 201Tl at stress, performed the first scan (image T1), then injected at rest 2 MBq/kg of 99mTc-tetrofosmin and immediately acquired a second scan with reconstruction in the energy window of thallium (image T2). A corrected thallium image was created by the subtraction of 99mTc downscattered photons (image TS). We compared spectra, image quality, and semiquantitative scores on T1, T2, and TS images.Results: Though T2 images were of worse quality, TS images were of equal quality compared to T1 images in most cases. Scores show an underestimation of abnormalities in 20% of patients on T2 images and in 10% on TS images.Conclusions: Despite the improved energy resolution of CZT cameras, downscatter of technetium in the 201Tl window leads to an underestimation of the pathological territory in 10% to 20% of cases. It does not allow us to use simultaneous dual-isotope acquisition in clinical practice without additional tools for scatter correction. [ABSTRACT FROM AUTHOR]

The identification of sentinel lymph nodes (SLNs) is important in deciding the resection range during surgery. 99mTc-labeled mannosylated human serum albumin (99mTc]Tc-MSA) is a radiopharmaceutical developed for SLN detection by targeting macrophages. Evans blue (EB) is a blue dye binding strongly to albumin and has been used for SLN detection. 99mTc]Tc-MSA-EB conjugate was prepared as a multi-modal imaging agent and tested its performance by visual investigation, fluorescence imaging and SPECT/CT for SLN mapping in mice. EB was mixed with various concentration of MSA to prepare MSA-EB conjugates. The binding efficiencies were determined using thin-layer chromatography. The UV-VIS spectra and molar extinction coefficient of the conjugate were obtained. The fluorescence was monitored at the excitation wavelength range 420–780 nm and the emission wavelength range 520–845 nm. The 99mTc]Tc-MSA-EB conjugate and EB were injected into the footpads of normal BALB/c mice to check the lymph node (LN) uptakes. The visible, fluorescence, and SPECT/CT images were obtained after injection. The conjugation of EB with MSA increased by time and was saturated within 10 min. The molar extinction coefficient of the conjugate was 99,259.3/M/cm at 620 nm. The uptake of conjugate into the popliteal LN after injection into the footpads of mice was investigated visually and fluorescence imaging. SPECT/CT images showed that the standardized uptake values of 99mTc]Tc-MSA-EB conjugate in popliteal LN were about 4 times higher than in sciatic LN at all timepoints. It was confirmed by investigating resected LN that the blue color, fluorescence, and radioactivity of the 99mTc]Tc-MSA-EB conjugate were retained only on the LN and did not spread to adjoining tissues. 99mTc]Tc-MSA-EB conjugate has a great potential as a multi-modal SLN mapping agent which could be detected by visual investigation, fluorescence imaging, and SPECT/CT. [ABSTRACT FROM AUTHOR]

Amount estimation of production of 99Mo required for medical applications was carried out by utilizing an electron linear accelerator with 30 g of natMoO3 target, and 15.10 MBq of 99Mo was obtained after 9.5 min of irradiation with bremsstrahlung photons by a 35 MeV-80 μA electron beam. Requirements for further scaled-up production with 100MoO3 target (100 g, φ20 mm × t30 mm) were analyzed using Monte Carlo simulation. It was found that it had to be irradiated with 20 h of bremsstrahlung photons by a 35 MeV-1 mA electron beam to produce 1340 GBq of 99Mo. [ABSTRACT FROM AUTHOR]

Background: For multicenter clinical studies, PET/CT and SPECT/CT scanners need to be validated to ensure comparability between various scanner types and brands. This validation is usually performed using hollow phantoms filled with radioactive liquids. In recent years, 3D printing technology has gained increasing popularity for manufacturing of phantoms, as it is cost-efficient and allows preparation of phantoms of almost any shape. So far, however, direct 3D printing with radioactive building materials has not yet been reported. The aim of this work was to develop a procedure for preparation of 99mTc-containing building materials and demonstrate successful application of this material for 3D printing of several test objects. Method: The desired activity of a [99mTc]pertechnetate solution eluted from a 99Mo/99mTc-generator was added to the liquid 3D building material, followed by a minute amount of trioctylphosphine. The resulting two-phase mixture was thoroughly mixed. Following separation of the phases and chemical removal of traces of water, the radioactive building material was diluted with the required volume of non-radioactive building material and directly used for 3D printing. Results: Using our optimized extraction protocol with trioctylphosphine as complex-forming phase transfer agent, technetium-99m was efficiently transferred from the aqueous 99Mo/99mTc-generator eluate into the organic liquid resin monomer. The observed radioactivity concentration ratio between the organic phase and the water phase was > 2000:1. The radioactivity was homogeneously distributed in the liquid resin monomer. We did not note differences in the 3D printing behavior of the radiolabeled and the unlabeled organic liquid resin monomers. Radio-TLC and SPECT studies showed homogenous 2D and 3D distribution of radioactivity throughout the printed phantoms. The radioactivity was stably bound in the resin, apart from a small amount of surface-extractable radioactivity under harsh conditions (ethanol at 50 °C). Conclusions: 3D printing of radioactive phantoms using 99mTc-containing building materials is feasible. Compared to the classical fillable phantoms, 3D printing with radioactive building materials allows manufacturing of phantoms without cold walls and in almost any shape. Related procedures with longer-lived radionuclides will enable production of phantoms for scanner validation and quality control. [ABSTRACT FROM AUTHOR]

The aim of this study is to find the optimum conditions of labeling luteolin flavonoid compounds with technetium-99m (99mTc) to meet the purity requirements stated in the United States Pharmacopeia. This compound is expected to be a potential radiotracer compound for diagnosing cancer. The optimization method in labeling luteolin with technetium determines the parameters such as pH, SnCl2.2H2O, genistein concentration, and incubation time. Optimization results of Technetium-99m-luteolin labeling obtained optimum pH conditions 8, the amount of SnCl2.2H2O as a reducing agent 60 μL, the optimum amount of luteolin 6 mg/ml, and the optimum incubation time is 30 min. This optimum condition obtained a99mTc-Luteolin radiochemical purity yield of 94.15%. The radiochemical purity percentage of the99mTc-Luteolin compound has fulfilled the requirements listed at United States Pharmacopeia, which is ≥90%. [ABSTRACT FROM AUTHOR]

Cellulose nanocrystals (CNCs) are known as nano-biomaterials that can be achieved from the different sources. The designated CNCs have been successfully fabricated from the roots of Dorema kopetdaghens (Dk) plant by sulphuric acid hydrolysis method. Structural analysis has been carried out by the means of XRD, FTIR, and TGA/DTG procedures. The XRD results have indicated that the crystalline structure of CNCs had been cellulose I with the crystallinity index of 83.20% and size of 4.95 nm. The FTIR spectra have shown that the resulting samples have been related to the cellulose species. The thermal properties of CNCs have exhibited a lower thermal stability in comparison to the untreated roots. It has been indicated by the morphological analyses of FESEM, TEM, and AFM that the nanoparticles had contained a spherical shape. Also, the cytotoxicity of CNCs against A549 cell line has not exhibited any cytotoxic effects. The analysis of labeling efficiency in regards to 99mTc-CNCs has been observed to be above 98%, while the biodistribution of radioactivity has displayed a high uptake by the kidneys and blood circulation. Therefore, it is possible to transform the low-cost by-product into a beneficial substance such as CNCs that can be utilized in bioimaging applications. Unlabelled Image • The production of CNCs from Dorema kopetdaghens plant by acid hydrolysis • CNCs have not caused any significant cellular toxicity effects on the A549 cells. • The direct labeling of CNCs by Tc-99m for diagnostic and bioimaging applications • Labeling efficiency of 99mTc-CNCs was >98%. • The biodistribution of radioactivity has displayed a high uptake by the kidneys. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of forced swimming on the technetium-99m (99mTc) labeling of blood constituents (BloCs). Rats (Wistar) were submitted to forced swim. In previous experiments, swimming animals would recover for different periods of time. Animals not submitted to swimming were used as control. Blood samples were obtained and the 99mTc labeling of BloCs was carried out. Blood cells (BCs), plasma (P), insoluble fractions (IF-P and IF-BCs), and soluble fractions (SF-P and SF-BC) were isolated. Radioactivity was determined, and the percentage of 99mTc incorporated (%ATI) was calculated in each fraction. Results showed that forced swimming decreased the percentage of 99mTc incorporated (%ATI) in IF-P (p < 0.05). It is suggested that the 99mTc labeling of BloCs could be used to verify the effects of the stress conditions on BloCs and that the radionuclide fixation on plasma proteins might be altered in rats submitted to acute stress induced by forced swimming, returning to control levels after recovery. [ABSTRACT FROM AUTHOR]

Molybdenum-99 (99Mo), in the form of 99Mo-alfa-benzoin oxime (99Mo-ABO) complex was developed as industrial radiotracer and its performance was tested in a diesel hydro-treater unit of a leading oil refinery. Main objective of the study was to evaluate the suitability of the developed 99Mo-ABO complex for industrial applications at high temperature and high-pressure hydrocarbon stream. A methodology was developed to convert the aqueous solution of fission 99Mo into 99Mo-ABO complex, suitable for mixing with organic phase. A radiotracer study was carried out to identify the leaky heat exchangers from a series of four heat exchangers using 99Mo-ABO complex in organic phase as a novel industrial radiotracer. Reproducibility of the result was verified by using 99mTc in organic phase as another radiotracer. From the study it was found that the developed radiotracer '99Mo-ABO complex' is suitable for industrial applications at high temperature and high-pressure hydrocarbon streams. [ABSTRACT FROM AUTHOR]