RT Journal Article SR Electronic T1 Safety, Dosimetry, and Feasibility of [68Ga]Ga-PSMA-R2 as an Imaging Agent in Patients with Biochemical Recurrence or Metastatic Prostate Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.124.268318 DO 10.2967/jnumed.124.268318 A1 Lindenberg, Liza A1 Hope, Thomas A. A1 Lin, Frank I. A1 Rowe, Steven P. A1 Pucar, Darko A1 Gilbert, Noella A1 Chicco, Daniela A1 He, Beilei A1 Feuerecker, Benedikt A1 Castaldi, Elena A1 Solnes, Lilja B. YR 2025 UL http://jnm.snmjournals.org/content/early/2025/02/06/jnumed.124.268318.abstract AB Prostate-specific membrane antigen (PSMA) is highly expressed in most prostate cancers (PCs). PET and CT imaging studies using 68Ga-labeled PSMA ligands demonstrated the specific localization of 68Ga in PC lesions and distant metastatic lesions. [68Ga]Ga-PSMA-R2 (68Ga-PSMA-R2) is a PSMA-targeted PET/CT radiotracer with potential diagnostic applications. Methods: PROfind (NCT03490032) was a phase 1/2, open-label, multicenter study of administration of 3 MBq/kg of 68Ga-PSMA-R2 (from >150 to ≤250 MBq) in patients with biochemical recurrence (BCR) or metastatic PC (mPC). Participants underwent baseline conventional imaging (CT/MRI or bone scan) and PET/CT. Whole-body PET/CT imaging sequences were obtained between 20 min and 4 h after injection. Primary endpoints were safety and tolerability; secondary endpoints included biodistribution, potential lesion identification, pharmacokinetics, and dosimetry. Potential lesions were identified by 2 masked expert panels; a third panel evaluated the identified lesions. Results: Six patients with BCR were enrolled into phase 1, and 24 patients with BCR or mPC (n = 12 each) into phase 2. Thirteen treatment-emergent adverse events were reported, including 1 serious adverse event (ileus), unrelated to drug administration. All adverse events were mild or moderate and deemed not related to 68Ga-PSMA-R2. Peak blood concentration of 68Ga-PSMA-R2 was typically observed approximately 5 min after injection, steadily decreasing over 6 h. Mean absorbed radiation dose was highest in the urinary bladder wall (0.120 mGy/MBq) and kidney (0.061 mGy/MBq). No other organ mean absorbed radiation dose exceeded 0.020 mGy/MBq. Mean absorbed radiation doses in the salivary and lacrimal glands were 0.016 and 0.008 mGy/MBq, respectively. Mean total body absorbed radiation dose was 0.014 mGy/MBq. Mean effective total body dose was 0.015 mSv/MBq (range, 0.012–0.018 mSv/MBq). 68Ga-PSMA-R2 PET/CT detected 85 lesions in 22 participants at 1 h after injection and 103 lesions in 22 participants at 2 h after injection. Conventional imaging detected 49 lesions in 8 participants with mPC but none in participants with BCR. Conclusion: 68Ga-PSMA-R2 was well tolerated, with no drug-related treatment-emergent adverse events. Safety and preliminary imaging performance data support further development of 68Ga-PSMA-R2 as a diagnostic agent in patients with PC.