In house development of (99m)Tc-Rhenium sulfide colloidal nanoparticles for sentinel lymph node detection.

In this study, rhenium sulfide colloidal nanoparticles were developed as radiopharmaceutical for sentinel lymph node detection. We directly used rhenium sulfide as a starting material for the preparation of colloidal nanoparticles. UV-visible spectrophotometry was used for characterization of in house developed colloidal particles. The size distribution of radioactive particles was studied by using membrane filtration method. The percentage of radiolabeled colloidal nanoparticles was determined by paper chromatography (PC). The study also includes in vitro stability, protein binding in human blood and bioevaluation in a rabbit model. The results indicate that 77.27 ± 3.26 % particles of size less than 20nm (suitable for lymphoscintigraphy) were radiolabeled. (99m)Tc labeled rhenium sulfide labeling efficacy with the radiometal is 98.5 ± 0.5%, which remains considerably stable beyond 5h at room temperature. Furthermore, it was observed that 70.2 ± 1.3% radiolabeled colloid complex showed binding with the blood protein. Bioevaluation results show the remarkable achievement of our radiopharmaceutical. The in house prepared (99m)Tc labeled rhenium sulfide colloidal nanoparticles reached the sentinel node within 15 min of post injection. These results indicate that (99m)Tc labeled rhenium sulfide colloid nanoparticles kit produced by a novel procedure seems of significant potential as a feasible candidate for further development to be used in clinical practice.

Understanding the radiolabelling mechanism of 99mTc-antimony sulphide colloid.

The chemistry of antimony trisulphide colloid (ATC) was examined to elucidate the radiolabelling mechanism with 99mTcO4(-). Ion exchange chromatography and atomic absorption spectrophotometry techniques determined ATC to be resistant to hydrolysis in 0.1M hydrochloric acid (HCl) at 25 degrees C or 100 degrees C (>97% recovery, Sb3+ absent). Hydrogen sulphide gas detected did not participate in the mechanism, where antimony trisulphide and 99mTcO4(-) in HCl/100 degrees C yielded 96% 99mTc-product from a K2S-free formulation (versus 98% when K2S was present). 99mTcO4(-) was reduced >90% by DMSA or dithiothreitol under the same conditions, identifying involvement of thiol groups. Infrared analysis of Re-ATC showed S=O bonds, indicating excess thiol groups at the colloid surface were oxidised at the expense of 99mTcO4(-) reduction.

Characterization and preliminary evaluation of ester-modified technetium-99m SNS/S mixed ligand complexes as potential brain perfusion agents.

Two novel [99mTc](SNS/S) mixed ligand complexes carrying a pendant ester function on the monothiolate coligand were synthesized. The corresponding oxorhenium and [99gTc]oxotechnetium complexes prepared at the macroscopic level and chemically characterized were used for structure assignment of [99mTc](SNS/S) complexes prepared at the nanomolar level. Enzymatic hydrolysis of the pendant ester group of [99mTc](SNS/S) mixed ligand complexes by esterase was investigated in vitro and compared with that of the ethyl cysteinate dimer, [99mTc]ECD. Preliminary biodistribution data in mice shows that the complexes are lipophilic and exhibit significant initial uptake in rodent brain.

Technetium-99m-sulfur colloid for lymphoscintigraphy: effects of preparation parameters.

UNLABELLED: There has been a resurgence in the use of lymphoscintigraphy for the external detection of lymph nodes for metastatic melanoma and breast tumors. Technetium-99m-antimony trisulfide colloid was the radiopharmaceutical developed for this procedure and was found to have a narrow distribution of small particles, 0.003-0.03 microns, but it was never approved by the FDA. Technetium-99m-sulfur colloid also forms particles and this article reports on the effects different preparation parameters have on its particle size distribution and stability. METHODS: Four groups of kits were evaluated, kits which utilized: (a) a reduced heating protocol with a new 99mTc-elution, (b) a reduced heating protocol with an old 99mTc-elution, (c) a prolonged heating protocol with a new 99mTc-elution and (d) a prolonged heating protocol with an old 99mTc-elution. The particle size distribution and the stability of the different 99mTc-sulfur colloid kit preparations were evaluated over 6 hr utilizing polycarbonate filters ranging from 0.03 to 10 microns. RESULTS: In vitro studies demonstrated no significant change in the particle size distribution over a 6-hr period and all 99mTc-sulfur colloid preparations had a bimodal particle size distribution pattern. Importantly, heating the kit for shorter periods of times utilizing [99mTc]pertechnetate, which had a longer ingrowth of [99mTc]pertechnetate, produced a formulation which had the largest percentage of particles smaller than 0.03 microns. CONCLUSION: In our clinical setting, 99mTc-sulfur colloid prepared with the reduced heating protocol and utilizing [99mTc]pertechnetate, which has the highest ingrowth of [99mTc]pertechnetate has proved to be an excellent agent for lymphoscintigraphy studies. This preparation has demonstrated rapid movement of the particles from the primary site to the lymph nodes in over 97% (106/109) of the patients we have studied.