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2000
Volume 16, Issue 3
  • ISSN: 1874-4710
  • E-ISSN: 1874-4729

Abstract

Introduction: The feasibility of preparing the “in-house” generators and the Th- DTPA(DOTA)-Nimotuzumab radioimmunoconjugate was evaluated. 226Th is perspective for TAT, however, due to short half-life it is preferable to apply this radionuclide for readily available epithelial malignancies. Nimotuzumab being specific for EGFR expressing cells as a targeting moiety is considered to be suitable for thorium delivery. Methods: TEVA extraction chromatographic resin and anion exchange resin AG 1x8 were used as sorbents for 226Th generator. In order to determine features of labeling by Th4+ we applied 234Th as a longer-lived analog of short-lived 226Th and the immunoconjugates DTPA(DOTA)-Nimotuzumab were used for radiolabeling. Results: The generator on the base of TEVA resin has shown higher volume activity of the product compared to the AG 1x8. The 226Th volume concentration was up to 80%/mL. The radiolabeling of BFCA by thorium radioisotopes reached 95% at the MR(Th:p-SCN-Bn-DTPA) = 1:100 and 86% for MR(Th:p-SCN-Bn-DOTA) = 1:5000 at 90°C. The procedure of Nimotuzumab labeling with Th4+ for radiotherapy of EGFR-overexpressing carcinomas was established. The overall labeling yield in both radioimmunoconjugates - DTPA and DOTA functionalized - was in the range of 45-50%. The immunoconjugate Nimotuzumab-p-SCN-Bn-DTPA was obtained with a molar ratio 1:25 (Nimotuzumab: BFCA), within 1 hour of conjugation at 25°C and labelled postconjugation approach. Whereas Nimotuzumab-p-SCN-Bn-DOTA was obtained at the same conditions, but radiolabeled by the method of pre-conjugation. Conclusion: 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.

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/content/journals/crp/10.2174/1874471016666230221102518
2023-09-01
2025-05-31
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