V. K. Tishchenko, A. V. Fedorova, O.F. Chibisova, N.B. Morozova, A. A. Lebedeva, S. P. Orlenko, A.A. Solyanov, A. A. Ostroukhov, O. Vlasova, A. Kaprin
tlooto Summary
Analysis of tumor/organs values showed that the concentration of 225Ac-DOTA-TOC and 225Ac-DOTA-TATE in tumor was higher than in most organs, except liver and kidneys, so 225Ac-DOTA-TATE was chosen for further preclinical studies.
Abstract
Purpose: Comparative studies of metal complexes 225Ac-DOTA-TOC and 225Ac-DOTA-TATE biodistribution in laboratory animals with an experimental model of malignant tumor and optimal radioconjugate determination for further preclinical studies.
Material and methods: Radiochemical synthesis of 225Ac-DOTA-TOC and 225Ac-DOTA-TATE metal complexes was carried out using chemical precursors DOTA-TOC and DOTA-TATE in lyophilic form (JSC Pharm-Sintez) and actinium-225 chloride (IPPE JSC). Biodistribution studies were performed in immunodeficient NU/J mice, females, with subcutaneously transplanted SK-Mel-28 melanoma. Biodistribution of radiopharmaceuticals was assessed ex vivo and measured by the radiometric method with an automatic gamma counter by the specific activity in samples of organs and tissues measurement.
Results: Radioconjugates 225Ac-DOTA-TOC and 225Ac-DOTA-TATE had similar biodistribution in tumor-bearing animals after a single intravenous administration. The highest accumulation of both radioconjugates was observed in the kidneys: 8.908–45.243 %ID/g and 3.816–25.694 %ID/g for 225Ac-DOTA-TOC and 225Ac-DOTA-TATE, respectively. The uptake of 225Ac-DOTA-TATE (0.179–3.869 %ID/g) in tumor was higher than 225Ac-DOTA-TOC (0.120–1.514 %ID/g), however, statistically significant differences (p < 0.05) were observed only at 5 min after administration. There were not statistically significant differences between the uptake of 225Ac-DOTA-TOC and 225Ac-DOTA-TATE in other organs and tissues. Analysis of tumor/organs values showed that the concentration of 225Ac-DOTA-TOC and 225Ac-DOTA-TATE in tumor was higher than in most organs, except liver and kidneys. The lowest uptake of both radiopharmaceuticals was registered in the brain (less than 0.1 %ID/g).
Conclusion: According to the results of this study, the radioconjugate 225Ac-DOTA-TATE has optimal biodistribution (higher accumulation in the tumor and lower in the kidneys as compared with 225Ac-DOTA-TOC), so 225Ac-DOTA-TATE was chosen for further preclinical studies.
Citation format
TISHCHENKO, V. K., et al. Biological distribution of radioconjugates based on somatostatin analogs and radionuclide actinium-225. Medical Radiology and Radiation Safety, 2026, 71(1): 67–72.