¹⁸F-labeled rhodamines as potential myocardial perfusion agents: comparison of pharmacokinetic properties of several rhodamines

Introduction: We recently reported the development of the [¹⁸F]fluorodiethylene glycol ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging (MPI). This compound was developed by optimizing the ester moiety on the rhodamine B core, and its pharmacokinetic properties were found to be superior to those of the prototype ethyl ester. The goal of the present study was to optimize the rhodamine core while retaining the fluorodiethyleneglycol ester prosthetic group. Methods: A series of different rhodamine cores (rhodamine 6G, rhodamine 101, and tetramethylrhodamine) were labeled with ¹⁸F using the corresponding rhodamine lactones as the precursors and [¹⁸F]fluorodiethylene glycol ester as the prosthetic group. The compounds were purified by semipreparative HPLC, and their biodistribution was measured in rats. Additionally, the uptake of the compounds was evaluated in isolated rat cardiomyocytes. Results: As was the case with the different prosthetic groups, we found that the rhodamine core has a significant effect on the in vitro and in vivo properties of this series of compounds. Of the rhodamines evaluated to date, the pharmacologic properties of the ¹⁸F-labeled diethylene glycol ester of rhodamine 6G are superior to those of the ¹⁸F-labeled diethylene glycol esters of rhodamine B, rhodamine 101, and tetramethylrhodamine. As with ¹⁸F-labeled rhodamine B, [¹⁸F]rhodamine 6G was observed to localize in the mitochondria of isolated rat cardiomyocytes. Conclusions: Based on these results, the ¹⁸F-labeled diethylene glycol ester of rhodamine 6G is the most promising potential PET MPI radiopharmaceutical of those that have evaluated to date, and we are now preparing to carry out first-in-human clinical studies with this compound