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

Imaging of PARP expression has emerged as valuable strategy for prediction of tumor malignancy. While [¹⁸F]PARPi and [¹⁸F]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 [¹⁸F]FPyPARP aims to bridge this gap with a higher renal clearance and an easily translatable synthesis route for potential clinical application.

We developed a less lipophilic variant of [¹⁸F]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 [¹⁸F]PARPi, [¹⁸F]FPyPARP, and [¹⁸F]FTT in NOD.CB17-Prkdc^scid/J mice bearing HCC1937 xenografts to assess xenograft uptake and pharmacokinetics focusing on excretion pathways.

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 [¹⁸F]PARPi, [¹⁸F]FPyPARP, and [¹⁸F]FTT), a partial shift from hepatobiliary to renal clearance of [¹⁸F]FPyPARP was observed, whereas [¹⁸F]PARPi and [¹⁸F]FTT show almost exclusive hepatobiliary clearance.

These findings imply that [¹⁸F]FPyPARP is an alternative to [¹⁸F]PARPi and [¹⁸F]FTT for PET imaging of PARP enzymes.