DTPA(DOTA)-Nimotuzumab Radiolabeling with Generator-produced Thorium for Radioimmunotherapy of EGFR-overexpressing Carcinomas

• Published in: Current radiopharmaceuticals Vol. 16; no. 3; p. 233
• Main Authors: Bravo, Magdiel G, Egorova, Bayirta V, Vasiliev, Aleksandr N, Lapshina, Elena V, Ermolaev, Stanislav V, Durymanov, Mikhail O
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 05.06.2023
• Subjects: Carcinoma; Cell Line, Tumor; ErbB Receptors - metabolism; Humans; Immunoconjugates - chemistry; Pentetic Acid; Radioimmunotherapy - methods; Radioisotopes; Radiopharmaceuticals; Thorium; thorium-226; growth factor receptor; radioimmunotherapy; radioimmunoconjugate; Alpha-emitter; epidermal
• ISSN: 1874-4729
• DOI: 10.2174/1874471016666230221102518

The feasibility of preparing the "in-house" generators and the Th- DTPA(DOTA)-Nimotuzumab radioimmunoconjugate was evaluated. Th 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. TEVA extraction chromatographic resin and anion exchange resin AG 1x8 were used as sorbents for Th generator. In order to determine features of labeling by Th4 we applied Th as a longer-lived analog of short-lived Th and the immunoconjugates DTPA(DOTA)-Nimotuzumab were used for radiolabeling. The generator on the base of TEVA resin has shown higher volume activity of the product compared to the AG 1x8. The Th 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. 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.