Dynamics, Pharmacokinetics, and Dosimetry of First-in-Human [⁶⁸Ga]Ga-OncoACP3-DOTA PET in Patients with Prostate...

This study aimed to investigate the dynamics, pharmacokinetic characteristics, and radiation dosimetry of [⁶⁸Ga]Ga-OncoACP3-DOTA, a novel prostatic acid phosphatase (ACP3)-targeted radioligand, in patients with metastatic castration-resistant prostate cancer. Methods: Seven patients with metastatic castration-resistant prostate cancer had dynamic or multiple-time-point PET/CT scans after intravenous injection of [⁶⁸Ga]Ga-OncoACP3-DOTA available. Five patients had early dynamic scans over the thorax, and 6 had dynamic whole-body PET scans during the first hour after injection. Five patients underwent an additional late-time-point whole-body PET scan (median, 3.2 h postinjection). SUVs for volumes of interest were determined for normal organs and metastases, and uptake dynamics and tumor-to-background ratios were calculated. Pharmacokinetic modeling was performed for multiple compartment models and evaluated in accordance with the Akaike information criterion. Dosimetry calculations were performed using MIRDfit and MIRDcalc, with time-integrated activity coefficients scaled to the International Commission on Radiological Protection 133 Adult Male Reference Phantom. Results: [⁶⁸Ga]Ga-OncoACP3-DOTA displayed declining uptake in most organs, except for organs involved in excretion, and stable uptake was observed only in the prostate. Dual renal and hepatobiliary excretion was noted. Declining blood kinetics were well-fitted by a triexponential function. Metastases showed an increase in uptake from early to late time points, with intensely increasing tumor-to-background ratios. Pharmacokinetic modeling indicated that a 2-tissue compartment model with irreversible binding was most appropriate for describing metastatic uptake. Bone and lymph node metastases exhibited significant differences in K ₁ and K _i values. The mean effective dose was 0.0192 mSv/MBq, resulting in an effective dose of 3.50 mSv for a standard injection of 2.5 MBq/kg. The highest absorbed doses were observed in bone marrow (0.0913 mGy/MBq), kidneys (0.0657 mGy/MBq), and liver (0.0563 mGy/MBq), whereas salivary glands showed a negligible absorbed dose (0.0135 mGy/MBq). Conclusion: [⁶⁸Ga]Ga-OncoACP3-DOTA demonstrated favorable pharmacokinetics with increasing tumor uptake and tumor-to-background ratios at later time points, suggesting potential benefits for delayed imaging, especially with high-sensitive PET systems or radiolabeling with isotopes with longer half-lives. The dosimetry profile was favorable, with a lower effective dose compared with many prostate-specific membrane antigen-targeted radiopharmaceuticals and negligible salivary gland uptake, potentially reducing side effects during radiopharmaceutical therapy. Future studies are warranted to evaluate its clinical value.