INTRODUCTION:meta-[123/131I]Iodobenzylguanidine (mIBG) is a clinical agent used for imaging neuroendocrine tumors, where uptake in tumor is via active transport mechanism through norepinephrine transporters (NET). Our group in past have evaluated a 99mTc-analogue of the above tracer, based on 99mTc-4 + 1 labeling approach, which exhibited significant affinity for NET but suffered from reduced specific uptake in comparison to reference standard no-carrier-added (n.c.a.) [125I]mIBG. The present work attempts to synthesize two new 99mTc-analogues of the radio-iodinated derivative following [99mTc]Tc(CO)31+ approach with an aim to improve the above specific uptake content.METHODS:Two different precursors, xylylenediamine and 1,3-bis(chloromethyl)benzene, were synthetically modified to yield meta-functionalized benzylguanidine derivatives bearing iminodiacetate (IDA) and aminoethylglycine (AEG) tridentate chelating moieties, respectively. These ligands were labeled with technetium-99m via [99mTc][Tc(CO)3(H2O)3]+ synthon to form desired radioactive complexes 9 and 10. The radiolabeling yields of the complexes obtained were >90% as confirmed by radio-HPLC. The HPLC purified complexes were used for in vitro and in vivo evaluation to understand the true biological efficacy. Structural characterization of the radiolabeled complexes was carried after synthesizing and characterizing their Re-analogues.RESULTS:Cell uptake studies with the radiolabeled complexes in SK-N-SH neuroblastoma cell lines revealed reduced uptake in the cells (<1% of incubated radioactivity/106 cells) in comparison to n.c.a. [125I]mIBG (~12%). However, limited specificity (~60%) was observed for the complexes as ascertained through desmethylimipramine (DMI) inhibition. Biodistribution studies in normal Wistar rats exhibited desired non-target clearance pharmacokinetics for the complexes but in vivo NET efficacy in myocardium for the neutral complex 10 could not be established.CONCLUSIONS:Tridentate [99mTc]Tc(CO)31+ chelation approach severely affects biological behavior of the present small bioactive molecule under study to a significant extent in comparison to monodentate ligation in 99mTc-4 + 1 strategy.

Introduction: meta-[I-123/131]Iodobenzylguanidine (mIBG) is a clinical agent used for imaging neuroendocrine tumors, where uptake in tumor is via active transport mechanism through norepinephrine transporters (NET). Our group in past have evaluated a Tc-99m-analogue of the above tracer, based on Tc-99m-4 + 1 labeling approach, which exhibited significant affinity for NET but suffered from reduced specific uptake in comparison to reference standard no-carrier-added (n.c.a.) [I-126]mIBG. The present work attempts to synthesize two new Tc-99m analogues of the radio-iodinated derivative following [Tc-99m]Tc(CO)(3)(1+) approach with an aim to improve the above specific uptake content. Methods: Two different precursors, xylylenediamine and 1,3-bis(chloromethyl)benzene, were synthetically modified to yield meta-functionalized benzylguanidine derivatives bearing iminodiacetate (IDA) and aminoethylglycine (AEG) tridentate chelating moieties, respectively. These ligands were labeled with technetium-99m via [Tc-99m][Tc (CO)(3) (H2O)(3)] (+) synthon to form desired radioactive complexes 9 and 10. The radiolabeling yields of the complexes obtained were >90% as confirmed by radio-HPLC. The HPLC purified complexes were used for in vitro and in vivo evaluation to understand the true biological efficacy. Structural characterization of the radiolabeled complexes was carried after synthesizing and characterizing their Re-analogues. Results: Cell uptake studies with the radiolabeled complexes in SK-N-SH neuroblastoma cell lines revealed reduced uptake in the cells (<1% of incubated radioactivity/10(6) cells) in comparison to n.c.a. [I-125]mIBG (similar to 12%). However, limited specificity (similar to 60%) was observed for the complexes as ascertained through desmethylimipramine (DMI) inhibition. Biodistribution studies in normal Wistar rats exhibited desired non-target clearance pharmacokinetics for the complexes but in vivo NET efficacy in myocardium for the neutral complex 10 could not be established. Conclusions: Tridentate [Tc-99m]Tc(CO)(3)(1+) chelation approach severely affects biological behavior of the present small bioactive molecule under study to a significant extent in comparison to monodentate ligation in Tc-99m-4 + 1 strategy. (C) 2019 Elsevier Inc. All rights reserved.

99mTc-ethylene dicysteine diethyl ester (99mTc-ECD) is an established radiopharmaceutical used for brain perfusion imaging; however it does not have any recognized biological quality control to ascertain its in vivo efficacy. The present paper describes an in vitro enzymatic method that can be adapted as a regular biological quality control for ECD kit evaluation before its release for patient end use. The method involves reaction of 99mTc-ECD (< 74 MBq; 0.1 mg ECD) with pig liver esterase enzyme (≥ 20 mg/mL) yielding metabolites in quantitative yield post 1 h incubation. Methodology developed is precise for routine quality control analyses of ECD kits.

123I/131I labeled meta-iodobenzylguanidine (mIBG) is a radiopharmaceutical used for diagnosis of neuroendocrine tumors (NET) related to neural crest origin. Present work evaluates a newly synthesized 99mTc analogue of this radioiodinated derivative.

The aim of the present study is to identify a99mTc-labeled fatty acid tracer which could be a possible substitute of the widely used123I-labeled fatty acids in studying myocardial metabolism and in detection of myocardial abnormalities.

We describe a simple method for the immobilisation of anti-thyroxine antibody on to the surface of polystyrene tubes and a simple assay format for the quantitative estimation of total thyroxine in serum. The immobilisation of anti-thyroxine antibody was achieved through passive adsorption of normal rabbit gamma globulin and anti-rabbit antibody raised in goat, as immune bridges. This procedure ensured minimum utilisation of primary and secondary antibody as neat sera without precipitation or affinity purification. The developed assay system using these antibody coated tubes covers a range of 0–240 ng/mL of thyroxine with intra and inter assay variations of less than 10 %.

Board of Radiation and Isotope Technology, India is a manufacturer and supplier of therapeutic doses of the 131I-meta-iodobenzylguanidine to various nuclear medicine centers in India. The therapeutic dosage of radiopharmaceutical involves a single variable dose of >3.7 GBq activity. Since the radiopharmaceutical produced is mainly by isotope exchange, which yields a low specific activity product, the determination of its accurate mass is a critical parameter for its safe administration in patients. In view of this, a suitable high performance liquid chromatography (HPLC) method has been developed for the determination of specific activity with high precision. Also, quantification of stability in terms of the % radiochemical purity of the formulation >370 MBq/mL supplied, under different storage conditions over time was carried out using the developed HPLC method.

[131I]-metaiodobenzylguanidine (mIBG) is a known radiopharmaceutical used for the treatment of neuroendocrine tumors. The development of therapeutic [131I]-mIBG doses at production level is highly challenging due to rapid product degradation and high radiation exposures to the production plant personnel. In the present work, a working module for the production of 10 doses (100mCi each) in a single operation was developed following copper (I) assisted isotope exchange. The labeled product complies with the pharmaceutical specifications suitable for in-vivo patient use.

The preparation of a single-component kit for 99m Tc-MIBI requires stringent control of lyophilization conditions. Hence, a two-components kit formulation, lyophilized under normal conditions, was standardized. The ligand was kept separate from the reductant stannous tin (preserved as stannous glucoheptonate) and advantage was taken of transchelation method, of Tc-GHA and Cu(I)-MIBI, for formation of Tc-MIBI. The product obtained was comparable in radiochemical purity (95 ± 2%), in heart uptake (2% injected dose) in rats and in blood clearance in rabbots, to that of the single-component kit/commercial product. Good-quality heart images in dog and monkey were also obtained.

A previous method was modified to obtain [99mTc(TBI)6]+ by reacting Zn(TBI)2Br2 directly with 99mTcO−4 in the presence of Sn2+ ions. [Cu(TBI)4]Cl was next used as a source of TBI. On reaction with 99mTcO−4 and Sn2+ ions for 3 min at 100 °C, [99mTc(TBI)6]+ product of radiochemical purity >90% and yield >70% was obtained. Data of biodistribution in rats (2–2.5% in heart) and biokinetics in rabbits were satisfactory. The kit formulation was found to be stable and also safe for administration.

The autonomously functioning thyroid nodule (AFTN) is a discrete, nodular structure which operates independently of pituitary control and without relation to the remaining thyroid tissue. Presently, for the visualization of a suppressed thyroid lobe, a patient has to undergo the thyrotropin (TSH) stimulation test, which has several disadvantages. In this study we have used tertiary butyl isonitrile (99mTc-TBI), well known as a myocardial imaging agent, for visualization of the suppressed lobe. Thirteen of fourteen patients studied demonstrated a contralateral lobe on a 99mTc-TBI scan which was not visualized with a 99mTc0(4) or 131I scan. Although it is not possible to demonstrate the autonomous nature of the hyperfunctioning thyroid nodule using 99mTc-TBI, we conclude that it is feasible to use this agent to visualize the lobe without the TSH test.

Radiopharmaceuticals (RPhs) are formulations containing radioisotopes, intended to be used on human beings for diagnosis & therapy. In Nuclear Medicine procedures, RPhs are administered either systemic route (by oral, intramuscular and intravenous) or instilled locally, consisting mainly liquid, solid and colloidal dosage forms. Therapeutic applications of Nuclear Medicine, is centered on the concept that particulate emitting radioisotopes (α, β particles) having the ability to ionize and