Gallium-68 PSMA-617

Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R-targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with ⁶⁸Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and ⁶⁸Ga-RM2 (⁶⁸Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm³), ⁶⁸Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and ⁶⁸Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered ⁶⁸Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of ⁶⁸Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 (P < 0.0001) or 2 (P = 0.0002). There were no significant differences in uptake between ISUP scores for ⁶⁸Ga-RM2. Median ⁶⁸Ga-RM2 SUV_max was significantly higher than median ⁶⁸Ga-PSMA-617 SUV_max in the ISUP-2 subgroup (P = 0.01). Conclusion: ⁶⁸Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and ⁶⁸Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions.

¹⁷⁷Lu-DKFZ-PSMA-617 is a promising treatment for patients with metastatic prostate cancer. Specific dosimetry for each patient is an important factor in planning the patient's treatment process. This study aimed to perform an image-based absorbed dose calculation for the treatment of metastatic prostate cancer with ¹⁷⁷Lu-DKFZ-PSMA-617.

The individualized patient dosimetry calculations were based on whole-body planar scintigraphy images acquired in 10 patients with a mean age of 71.4 ± 6.07 years (range 63-85 years) at approximately 0-2 h, 4-6 h, 18-24 h, and 36-48 h after administration of the mean 6253 ± 826.4 MBq (range 5500-7400 MBq) of ¹⁷⁷Lu-DKFZ-PSMA-617. Time-activity curves were generated for various organs. For count conversion to activities, calibration factors were calculated. Finally, the absorbed dose for an individual cycle was calculated using IDIAC-DOSE 2.1 software.

On average, the calculated absorbed dose for the kidneys and salivary glands were 0.46 ± 0.09 mGy/MBq and 0.62 ± 0.07 mGy/MBq, respectively.

Based on the results, the¹⁷⁷Lu-PSMA-617 therapy is a safe method for the treatment of castration-resistant prostate cancer patients. Large inter-individual variations in organ dose were found, demonstrating the need for patient-specific dosimetry and treatment planning.