Evaluation of genotoxic potential of peptides used in nuclear medicine (PSMA -617 and -11, and ubiquicidine 29-41) using a flow-cytometric, semi-automated analysis of micronuclei frequency in cell cultures

Abstract

Assays that rely on the assessment of frequency of micronuclei are important standard techniques currently used to quantify potential genotoxic damage after exposure to chemical or physical agents, such as ionizing radiation, or in pre-clinical studies, to assessment of the genotoxic potential of drugs or its components. The experiments are usually performed using conventional microscopy, but currently the protocols are being upgraded to automated approaches based on flow cytometry protocols based on the elimination of the plasma membrane by chemical agents, allowing quantification by flow cytometry. In this work, the genotoxic potential of peptides used as components of radiopharmaceuticals (PSMA-617 and 11 and Ubiquicidine) was evaluated exposing CHO-KI cells to a wide range of concentration (0.1X and 100X the maximum allowed concentration to human adults). Incubation with PSMA-11 or UBI29–41 did not induce genotoxicity. After 24 h of incubation, PSMA-617 induced genotoxicity only in non-practical concentration (100-fold). Results corroborate the safety of the predrugs and the wide detection range of technique.