Functional Suitability Evaluation of Radioimmunoconjugates of Nanobodies against PD-L1 and HER2/neu for Tumor Theranostics.

UNLABELLED: The aim of the study was to evaluate the applicability of radioimmunoconjugates (RIC) of nanobodies against PD-L1 and HER2/ neu for the diagnosis and therapy of malignant tumors.

MATERIALS AND

METHODS

The nanobodies to human biomarkers PD-L1 and HER2/neu were conjugated with radionuclides 68Ga and 177Lu using the chelating agent DOTA. RIC biodistribution was studied in experimental models on F1 (DBA/2xBALB/c) mice, which were inoculated with genetically modified CT26 murine carcinoma cells expressing human PD-L1 or HER2/neu. RICs containing the isotope 68Ga and intended for tumor detection were administered to animals intravenously at a dose of 1.0-1.2 MBq. In 0.5, 1.5, and 4 h the radioactivity accumulation in specific tumors carrying human biomarkers was assessed using direct dosimetry compared with control tumors. RICs containing 177Lu were administered for therapy at a dose of 0.8-1.6 MBq, and studied similarly for 96 h after administration. Results. After RICs containing 68Ga were administered to mice, the greatest difference between specific and control tumors was observed in 1.5 h. At the same time, there was a multiple excess of the specific tumor radioactivity over the blood and muscle tissue radioactivity, which should provide high contrast imaging. After administering RICs containing 177Lu to mice, the radioactivity in specific tumors persisted for 48 h producing a long-term effect of the radioisotope on the tumor. With the introduction of all RICs, there was a rapid elimination of radioactivity from the blood through urine, which was associated with the use of nanobodies with a molecular weight of 13 kDa and not containing sites of interaction with Fc receptors. There were found the significant accumulation and long-term retention of radioactivity in the kidneys. The work revealed a dependence of the radioactivity biodistribution on the isotope used: the time-normalized radioactivity of some organs and tissues, including tumors, after the administration of RICs containing 68Ga appeared to be higher than after administering the RICs of the same specificity, but containing 177Lu radioisotopes.

CONCLUSION

The findings indicated the functional suitability of the pairs of RIC nanobodies with 68Ga and 177Lu radioisotopes for theranostics of malignant tumors expressing PD-L1 and HER2/neu biomarkers.