Evaluation of INR101, a PSMA-Targeted 18F PET Tracer, for suspected prostate cancer: A multicenter phase I/IIa trial with histopathologic confirmation

Prostate cancer (PCa) is one of the most common malignancies among men worldwide. Early detection relies heavily on imaging accuracy, yet conventional modalities such as CT and MRI have limitations in identifying early-stage lesions. INR101 is a novel 18F-labeled PSMA-targeted PET tracer with high binding affinity, favorable biodistribution, and promising lesion detection capabilities for initial PCa diagnosis. INR101 was prepared and confirmed on radiochemical purity by HPLC to be > 93%. Entire production process was carried out in a manufacturing facility compliant with cGMP standards, and each production batch was tested for sterility and endotoxin levels. This multicenter, prospective, open-label Phase I/IIa trial included 8 healthy male volunteers (Phase I) and 24 treatment-naive patients with suspected prostate cancer (PSA ≥ 3 ng/mL, scheduled for biopsy; Phase IIa). Phase I evaluated safety, pharmacokinetics, biodistribution, and dosimetry of INR101 (9 ± 1 mCi). Phase IIa randomized patients 1:1 to 7 ± 1 mCi (n = 12) or 9 ± 1 mCi (n = 12) groups, with PET/CT scans at 80 ± 10 and 120 ± 10 min post-injection. Primary endpoints: Phase I (safety/dosimetry); Phase IIa (diagnostic efficacy vs. biopsy pathology). Exploratory endpoint: INR101 vs. mpMRI. The study was approved by ethics committees (2024LP01109) and registered (ChiCTR20240522, NCT06472531). In Phase I, INR101 showed rapid systemic distribution with primary uptake in the liver, kidneys, and salivary glands and a mean effective radiation dose was 7.6 ± 1.2 mSv. In Phase IIa trial, sensitivity, specificity, and accuracy of the low-dose group (7 ± 1 mCi), reached 100% (95% CI:39.8%-100.0%), 85.7% (95% CI:42.1%-99.6%), and 90.9% (95% CI:58.7%-99.8%), respectively; while that of the high-dose group (9 ± 1 mCi) were 87.5% (95% CI: 47.35%, 99.68%), 75.0% (95% CI: 19.41%, 99.37%), and 83.3% (95% CI: 51.59%, 97.91%). INR101 PET/CT demonstrated higher specificity and accuracy than multiparametric MRI. [low-dose group (7 ± 1 mCi): specificity 85.7% (95% CI:42.1%-99.6%) vs. mpMRI 60.0% (95% CI:14.7%-94.7%); accuracy 90.9% (95% CI:58.7%-99.8%) vs. mpMRI 78.3% (95% CI:56.3%-92.5%)], with no statistical significance (p > 0.05). No serious adverse events occurred in either Phase I or IIa. INR101 is safe and well-tolerated, with high diagnostic accuracy for detecting PSMA-positive prostate lesions. Optimal imaging was achieved at 7 ± 1 mCi with an uptake time of 80–120 min. Its favorable pharmacokinetics and superior diagnostic performance with low urinary tract interference suggest that INR101 PET/CT may be a valuable tool for early PCa detection, meriting further validation in larger clinical studies.