Organic Cation Transporter-Mediated Accumulation of Quinolinium Salts in the LV Myocardium of Rodents

PURPOSE: Quaternary ammonium salts have demonstrated marked accumulation in the left ventricular (LV) myocardium of rodents and swine. To investigate the mechanism underlying this uptake, the present study examined the interaction of [(18)F]fluoroethylquinolinium ([(18)F]FEtQ) with the family of organic cation transporters (OCTs). PROCEDURES: The cellular uptake of [(18)F]FEtQ into HEK293 cells, expressing human OCT1, -2, or -3 (HEK293-hOCT), and its inhibition by corticosterone was evaluated in vitro. The inhibitory effect of decynium 22 (D 22) in vivo was also studied, using PET/CT of HEK293-hOCT tumor-bearing mice. Furthermore, the distribution kinetics of [(18)F]FEtQ were determined in rats, with and without pre-administration of corticosterone, and following administration to a non-human primate (NHP). RESULTS: The accumulation of [(18)F]FEtQ in HEK293-hOCT cells was 15–20-fold higher than in control cells and could be inhibited by corticosterone. in vivo, the uptake of [(18)F]FEtQ in the LV myocardium of corticosterone-treated rats was significantly reduced compared to that of untreated animals. Similarly, following administration of D 22 to HEK293-hOCT tumor-bearing mice, the peak tumor uptake of [(18)F]FEtQ was reduced by 40–45 % compared to baseline. Contrary to the distinct accumulation of [(18)F]FEtQ in the LV myocardium of rats, no cardiac uptake was observed following its administration to a NHP. CONCLUSIONS: The quinolinium salt derivative [(18)F]FEtQ interacts with the family of OCTs, and this interaction could account, at least in part, for the increased uptake in the LV myocardium of rodents. Nonetheless, its low affinity for hOCT3 and the results of PET/CT imaging in a NHP indicate a limited clinical applicability as a radiopharmaceutical for cardiac and/or OCT imaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11307-022-01728-y.