[68Ga]Ga-OncoACP3 PET imaging defines acid phosphatase 3 as a clinically actionable theranostic target in prostate cancer: a prospective phase I trial

Background and Rationale Acid Phosphatase 3 (ACP3) has extive theranostic target to Prostate-Specific Membrane Antigen (PSMA) in prostate cancer. Gallium-68 labelled OncoACP3 ([ 68 Ga]Ga-OncoACP3), a high-affinity small organic radioligand for human ACP3, has shown encouraging properties in preclinical experiments. In this prospective Phase I study, we assessed the safety, the dosimetry, pharmacokinetics, and preliminary positron emission tomography (PET) imaging findings of [ 68 Ga]Ga-OncoACP3. Methods Prostate cancer patients received a single administration of 250 (150–275) MBq of [ 68 Ga]Ga-OncoACP3, followed by PET/CT scans at 0, 10, 60, and 120 min. Blood and urine samples were serially collected. Safety was assessed for up to 1 week after imaging. Adverse events were recorded and graded according to CTCAE v.5. Dosimetry was evaluated centrally based on PET/CT scans and blood and urine radioactivity measurements. Pharmacokinetics were assessed using serial blood samples. Uptake in lesions and healthy organs was evaluated visually and semi-quantitatively. Imaging findings were compared to PSMA PET, when available within 4 weeks, and histopathology data. Results A total of 20 patients were enrolled. No adverse events related to the administration of [ 68 Ga]Ga-OncoACP3 were recorded. The whole-body effective dose was 1.91*10 -2 mSv/MBq. [ 68 Ga]Ga-OncoACP3 showed a mixed renal and hepatobiliary excretion, with rapid and selective tumour uptake. [ 68 Ga]Ga-OncoACP3 PET/CT was positive in 17/20 patients and negative in 3/20 cases—all three cases also presenting a negative PSMA PET. Among patients whose final diagnosis was also confirmed histologically, [ 68 Ga]Ga-OncoACP3 was true positive in 8/9 subjects. [ 68 Ga]Ga-OncoACP3 demonstrated cleaner biodistribution than PSMA, with no salivary gland uptake visualisation and no unspecific bone uptakes. Conclusions [ 68 Ga]Ga-OncoACP3 was safe. The dosimetry profile is consistent with that of other clinically used diagnostic radiopharmaceuticals. [ 68 Ga]Ga-OncoACP3 showed optimal pharmacokinetics with rapid tumour uptake and clearance from healthy organs. [ 68 Ga]Ga-OncoACP3 demonstrated promising characteristics for PET imaging of prostate cancer, supporting ACP3 as a clinically actionable theranostic target.