biostudies-literatureDurinova AGrantová Agentura, Univerzita KarlovaNETPHARM32https://www.ebi.ac.uk/biostudies/studies/S-EPMC11026318biostudies-literatureUnknown9(1)<h4>Background</h4>Megalin (LRP2 receptor) mediates the endocytosis of radiolabeled peptides into proximal tubular kidney cells, which may cause nephrotoxicity due to the accumulation of a radioactive tracer. The study aimed to develop a cellular model of human kidney HK2 cells with LRP2 knockout (KO) using CRISPR/Cas9 technique. This model was employed for the determination of the megalin-mediated accumulation of ⁶⁸Ga- and ^99mTc-labeled 15-mer peptide developed to target the vascular endothelial growth factor (VEGF) receptor in oncology radiodiagnostics.<h4>Results</h4>The gene editing in the LRP2 KO model was verified by testing two well-known megalin ligands when higher viability of KO cells was observed after gentamicin treatment at cytotoxic concentrations and loEJNMMI radiopharmacy and chemistryRadiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model.PMC11026318150120CZ.02.01.01/00/22_008/0004607Durinova ASchmierer BKamaraj RSmutna LBarta PPavek PSmutny TTrejtnar FfalseRadiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model.<h4>Background</h4>Megalin (LRP2 receptor) mediates the endocytosis of radiolabeled peptides into proximal tubular kidney cells, which may cause nephrotoxicity due to the accumulation of a radioactive tracer. The study aimed to develop a cellular model of human kidney HK2 cells with LRP2 knockout (KO) using CRISPR/Cas9 technique. This model was employed for the determination of the megalin-mediated accumulation of ⁶⁸Ga- and ^99mTc-labeled 15-mer peptide developed to target the vascular endothelial growth factor (VEGF) receptor in oncology radiodiagnostics.<h4>Results</h4>The gene editing in the LRP2 KO model was verified by testing two well-known megalin ligands when higher viability of KO cells was observed after gentamicin treatment at cytotoxic concentrations and lo2024-01-01T00:00:00Z2024 Apr2026-05-29T12:23:35.453Z2026-05-19T03:07:31.87ZS-EPMC110263183863734710.1186/s41181-024-00262-2