B. Egorova, M. Bravo, A. Vasiliev
Feb 21, 2023
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Quality indicators
Journal
Current radiopharmaceuticals
Abstract
INTRODUCTION Thorium-226 is a promising radioisotope for radioimmunotherapy. Here, we have prepared two "in-house" 230Pa/230U/226Th tandem generators consisting of an anion exchanger AG 1x8 and extraction chromatographic sorbent TEVA resin. METHOD Developed "direct" generators resulted in the production of 226Th with high yield and purity as required for biomedical applications. Next, we prepared Nimotuzumab radioimmunoconjugates with thorium-234, a long-living analog of 226Th, using bifunctional chelating agents (BFCAs) p-SCN-Bn-DTPA and p-SCN-Bn-DOTA. Radiolabeling of Nimotuzumab with Th4+ was carried out by post-labeling method, using p-SCN-Bn-DTPA, and pre-labeling method, using p-SCN-Bn-DOTA. RESULT Kinetics of p-SCN-Bn-DOTA complex formation with 234Th was studied at different molar ratios and temperatures. We found that optimal molar ratio 1:25 of Nimotuzumab to both BFCAs resulted in 8 to 13 molecules of BFCA per mAb molecule as was shown by size-exclusion HPLC. CONCLUSION The molar ratios of Th:BFCA of 1:5000 for p-SCN-Bn-DOTA and 1:100 for p-SCN-Bn-DTPA were found to be optimal and resulted in 86-90% RCY for both BFCAs complexes. Thorium-234 incorporation into both radioimmunoconjugates reached 45-50%. It has been shown that Th-DTPA-Nimotuzumab radioimmunoconjugate specifically bound with EGFR overexpressing epidermoid carcinoma A431 cells.