Two experts and a newbie: [(18)F]PARPi vs [(18)F]FTT vs [(18)F]FPyPARP—a comparison of PARP imaging agents

PURPOSE: Imaging of PARP expression has emerged as valuable strategy for prediction of tumor malignancy. While [(18)F]PARPi and [(18)F]FTT are already in clinical translation, both suffer from mainly hepatobiliary clearance hampering their use for detection of abdominal lesions, e.g., liver metastases. Our novel radiotracer [(18)F]FPyPARP aims to bridge this gap with a higher renal clearance and an easily translatable synthesis route for potential clinical application. METHODS: We developed a less lipophilic variant of [(18)F]PARPi by exchange of the fluorobenzoyl residue with a fluoronicotinoyl group and automated the radiosyntheses of the three radiotracers. We then conducted a comparative side-by-side study of [(18)F]PARPi, [(18)F]FPyPARP, and [(18)F]FTT in NOD.CB17-Prkdc(scid)/J mice bearing HCC1937 xenografts to assess xenograft uptake and pharmacokinetics focusing on excretion pathways. RESULTS: Together with decent uptake of all three radiotracers in the xenografts (tumor-to-blood ratios 3.41 ± 0.83, 3.99 ± 0.99, and 2.46 ± 0.35, respectively, for [(18)F]PARPi, [(18)F]FPyPARP, and [(18)F]FTT), a partial shift from hepatobiliary to renal clearance of [(18)F]FPyPARP was observed, whereas [(18)F]PARPi and [(18)F]FTT show almost exclusive hepatobiliary clearance. CONCLUSION: These findings imply that [(18)F]FPyPARP is an alternative to [(18)F]PARPi and [(18)F]FTT for PET imaging of PARP enzymes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05436-7.