Automated Radiolabeling and Evaluation of [F]FPMBBG: A Novel Cardiac Neuronal PET Imaging Agent.

This study reports the automated radiosynthesis and evaluation of [F]FPMBBG, a radiopharmaceutical designed to target the norepinephrine transporter (NET). A newly developed fully protected benzylguanidine precursor, which prevents interference from non-protected benzylguanidine part during the nucleophilic process, has enabled a one-pot two-step fully automated cassette-based synthesis of [F]FPMBBG. This advancement enhances the feasibility of the synthesis, ensures reproducibility, and allows for the production of substantial quantities of the radiotracer, paving the way for future clinical applications. [F]FPMBBG was prepared in radiochemical yield of ~ 23% (n = 6, decay-corrected) within 70 min, with a radiochemical purity exceeding 98%, and molar activity of > 2 GBq/μmol. In studies using miniature Bama pigs, [F]FPMBBG showed favorable distribution, providing high-contrast cardiac images at an early stage. Moreover, desipramine inhibition studies confirmed the high NET specificity of [F]FPMBBG. The efficient automated synthesis, robust heart uptake, and minimal background signal highlight [F]FPMBBG as a promising PET tracer for assessing cardiac sympathetic neuronal function.