Diagnostic Performance of ACP3-Targeted PET Imaging in Patients With Primary and Recurrent Prostate Cancer: An Open-Label, Single-Arm, Single-Center Study

Background Prostate cancer is the second most common cancer in men worldwide. Accurate diagnosis, staging, and risk stratification are critical for optimal management. PSMA PET imaging has improved prostate cancer detection but has limitations, including heterogeneous PSMA expression leading to false negatives, and physiological uptake in salivary glands, liver, spleen, and intestine that can obscure lesions or cause false-positive findings. ACP3 (prostate acid phosphatase, PAP) is highly and homogeneously expressed in more than 95% of prostate cancer lesions but has low expression in healthy tissues. OncoACP3 is a small-molecule ligand with picomolar affinity for ACP3. Preclinical and early clinical studies suggest that [68Ga]Ga-OncoACP3 PET has favorable biodistribution, low background uptake, and high tumor-to-background ratios, potentially outperforming PSMA PET in certain settings.

Study Objectives Primary objective: To prospectively evaluate the lesion detection rate and diagnostic performance (including sensitivity, specificity, accuracy, positive predictive value, and negative predictive value) of [68Ga]Ga-OncoACP3 PET imaging in men with clinically suspected or confirmed high-risk prostate cancer, or suspected recurrence after treatment.

Secondary objectives: (1) comparison with [68Ga]Ga-PSMA PET imaging in participants who have already undergone clinically routine PSMA PET; (2) correlation of semi-quantitative parameters derived from [68Ga]Ga-OncoACP3 PET imaging with pathological markers (ACP3 expression assessed by immunohistochemistry in tumor tissue); (3) evaluation of the impact of [68Ga]Ga-OncoACP3 PET imaging on clinical treatment decisions.

Study Design This is a prospective, single-arm, single-center, open-label clinical study enrolling 50 male participants aged 18 to 90 years with clinically suspected or confirmed high-risk prostate cancer, or suspected recurrence after treatment. After enrollment and informed consent, participants will undergo [68Ga]Ga-OncoACP3 PET/CT imaging within 1 week. A single intravenous dose of 3-5 mCi [68Ga]Ga-OncoACP3 will be administered, followed by PET/CT imaging at 1 hour post-injection. For participants who have already undergone clinically routine PSMA PET imaging, a comparison between the two imaging modalities will be performed. Image analysis will include visual qualitative assessment and semi-quantitative analysis (e.g., standardized uptake value). The gold standard for diagnosis will be histopathological examination and/or clinical follow-up of at least 6 months. The study will also assess the correlation between semi-quantitative PET parameters and ACP3 expression in tumor tissue, and evaluate the impact of imaging findings on clinical management.

Inclusion criteria

• 1. Voluntary participation and signed written informed consent before any study-specific procedures; 2. Male, aged 18 to 90 years; 3. Clinically suspected high-risk, histologically confirmed, or suspected recurrent prostate cancer after treatment; 4. Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study-related procedures; 5. Expected survival time greater than 6 months; 6. Participants' partners agree to use reliable contraceptive measures (such as abstinence, sterilization surgery, oral contraceptives, injectable medroxyprogesterone acetate, or subdermal implants) during the study and for at least 6 months after the last dose of study drug.

Exclusion criteria

• 1. Known or suspected allergy to [68Ga]Ga-OncoACP3 injection or any of its excipients; 2. Any severe unstable disease (e.g., severe cardiac, pulmonary, hepatic, or renal insufficiency) that, in the investigator's judgment, makes the participant unsuitable for the study; 3. Inability to complete PET/CT examination, including inability to lie flat, claustrophobia, or radiophobia; 4. Poor compliance or any other condition that, in the investigator's judgment, makes the participant unsuitable for the study; 5. Prior use of a radiopharmaceutical within less than 10 physical half-lives before study drug administration; 6. Currently participating in or planning to participate in any drug or device clinical trial during the study period.