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

Autor:	Bravo MG; Department of Chemistry, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russia.; The Center of Isotopes (CENTIS), Ave. Monumental y Carretera La Rada, Km 3 1/2, CP 32700, San Jose de las Lajas, Mayabeque, Republic of Cuba., Egorova BV; Department of Chemistry, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russia., Vasiliev AN; Department of Chemistry, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russia.; Institute for Nuclear Research of Russian Academy of Sciences, 60th October Anniversary Prospect, 7a, Moscow, 117312, Russia., Lapshina EV; Institute for Nuclear Research of Russian Academy of Sciences, 60th October Anniversary Prospect, 7a, Moscow, 117312, Russia., Ermolaev SV; Institute for Nuclear Research of Russian Academy of Sciences, 60th October Anniversary Prospect, 7a, Moscow, 117312, Russia., Durymanov MO; Department of Biophysics Moscow Institute of Physics and Technology, 9 Institutsky per., Dolgoprudny, Moscow Region, 141700, Russia.
Jazyk:	angličtina
Zdroj:	Current radiopharmaceuticals [Curr Radiopharm] 2023 Jun 05; Vol. 16 (3), pp. 233-242.
DOI:	10.2174/1874471016666230221102518
Abstrakt:	Introduction: The feasibility of preparing the "in-house" generators and the Th- DTPA(DOTA)-Nimotuzumab radioimmunoconjugate was evaluated. 226 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. Methods: TEVA extraction chromatographic resin and anion exchange resin AG 1x8 were used as sorbents for 226 Th generator. In order to determine features of labeling by Th4 + we applied 234 Th as a longer-lived analog of short-lived 226 Th 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 226 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 via 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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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