PET imaging of PARP expression using (68)Ga-labelled inhibitors

PURPOSE: Imaging the PARP expression using (18)F probes has been approved in clinical trials. Nevertheless, hepatobiliary clearance of both (18)F probes hindered their application in monitoring abdominal lesions. Our novel (68)Ga-labelled probes aim for fewer abdominal signals while ensuring PARP targeting by optimizing the pharmacokinetic properties of radioactive probes. METHODS: Three radioactive probes targeted PARP were designed, synthesized, and evaluated based on the PARP inhibitor Olaparib. These (68)Ga-labelled radiotracers were assessed in vitro and in vivo. RESULTS: Precursors that did not lose binding affinity for PARP were designed, synthesized, and then labelled with (68)Ga in high radiochemical purity (> 97%). The (68)Ga-labelled radiotracers were stable. Due to the increased expression of PARP-1 in SK-OV-3 cells, the uptake of the three radiotracers by SK-OV-3 cells was significantly greater than that by A549 cells. PET/CT imaging of the SK-OV-3 models indicated that the tumor uptake of (68)Ga-DOTA-Olaparib (0.5 h: 2.83 ± 0.55%ID/g; 1 h: 2.37 ± 0.64%ID/g) was significantly higher than that of the other (68)Ga-labelled radiotracers. There was a significant difference in the T/M (tumor-to-muscle) ratios between the unblocked and blocked groups as calculated from the PET/CT images (4.07 ± 1.01 vs. 1.79 ± 0.45, P = 0.0238 < 0.05). Tumor autoradiography revealed high accumulation in tumor tissues, further confirming the above data. PARP-1 expression in the tumor was confirmed by immunochemistry. CONCLUSION: As the first (68)Ga-labelled PARP inhibitor, (68)Ga-DOTA-Olaparib displayed high stability and quick PARP imaging in a tumor model. This compound is thus a promising imaging agent that can be used in a personalized PARP inhibitor treatment regimen. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-023-06249-6.