PSMA-targeted PET with [⁶⁸Ga]Ga-P16-093: Initial evaluation in intermediate-risk and high-risk prostate cancer patients prior to prostatectomy

Objectives: To assess performance of [⁶⁸Ga]Ga-P16-093, a PSMA-targeted PET radiopharmaceutical, for tumor imaging in ten intermediate-risk or high-risk prostate cancer patients independently scheduled for prostatectomy.

Methods: Based on pre-surgical biopsy, 2-patients had Gleason 4+5 lesions; 1-patient had a Gleason 4+4 lesion; 3-patients had Gleason 4+3 lesions; 1-patient had a Gleason 3+5 lesion; and 3-patients had Gleason 3+4 lesions. List-mode PET (0-55 minutes) was initiated upon i.v. [⁶⁸Ga]Ga-P16-093 administration (216 ± 6 MBq; IND 133,222) using a single bed position ranging from above the iliac crest to the lower pelvis. To quantitatively assess tracer kinetics the data were reconstructed by filtered back-projection, in addition to standard iterative reconstructions using various framing periods to maximize the observed counts while avoiding possible interference from urine radioactivity. In addition to standard surgical pathology, whole-mount prostate pathology was obtained for 8 of the 10 subjects for comparison with the PET findings.

Results: [⁶⁸Ga]Ga-P16-093 PET defined the location of lesions within the prostate in 8 of the 10 subjects. In post-surgical pathology, one subject had Gleason 4+5 disease (70%:30%), and showed extremely avid lesion uptake. Five subjects had Gleason 4+3 disease, all with lesions readily identified in the PET images. Three subjects had Gleason 3+4 disease; and one had Gleason 3+3 disease. PET was read as positive in the two Gleason 3+4 subjects with disease reported as Gleason 3 (73%):Gleason 4 (25%):Gleason 5 (2%), and Gleason 3 (80%):Gleason 4 (15%):Gleason 5 (5%), but negative for the other Gleason 3+4 subject reported as Gleason 3 (95%):Gleason 4 (5%). PET was also negative in the subject with Gleason 3+3 disease (100% Gleason Pattern 3). As observed in prostate cancer patients with biochemical recurrence (1), [⁶⁸Ga]Ga-P16-093 cleared relatively rapidly from blood and provided significant tumor/background contrast by 5-10 minutes post-injection. In general, ⁶⁸Ga uptake in the prostate lesions had peaked by ~15-minutes post-injection, and then remained stable throughout the remaining 40-minutes of imaging. The sole exception was the subject with Gleason 4+5 disease, in whom tumor uptake increased progressively from a concentration of 21 %ID/L at 15-min. to 28 %ID/L by 55-minutes. In the remaining seven subjects with PET-identified disease, tumor uptake over 15-55 minutes post-injection averaged 5.5±1.3 %ID/L (median 5.6 %ID/L; max 7.9 %ID/L; min 4.0 %ID/L). Over this same 15-55 minute time frame, across all 10 subjects normal muscle uptake averaged 0.57±0.06 %ID/L (median 0.56; max 0.64; min 0.47 %ID/L), while uptake in “normal” prostate regions averaged 2.3±0.4 %ID/L (median 2.4, max 2.9, min 1.6 %ID/L). Within this limited sample, radiopharmaceutical uptake exceeding 3.0 %ID/L discriminated PET-identified prostate lesions from normal prostate, as did a lesion/muscle ratio exceeding 6.0. Concordant with the post-surgical pathology, [⁶⁸Ga]Ga-P16-093 PET detected metastatic disease in several regional lymph nodes of the patient with high-risk (Gleason 4+5) disease. In the remaining subjects there was only one pathology-reported positive lymph node, a <1-mm lesion, which was not detected in the PET images.

Conclusions: In this initial assessment, the [⁶⁸Ga]Ga-P16-093 radiopharmaceutical appears suitable for mapping the location of clinically significant disease within the prostate of patients with intermediate- and high-risk prostate cancer. Beyond 15-minutes post-injection, tumor/background contrast only marginally improved with elapsed time. Therefore, in protocol design, consideration should be given to the implicit trade-off between any gain in target/background contrast from delayed imaging, and the attendant decline in tissue-of-interest photon flux due to the short half-life of ⁶⁸Ga. Supported by R44CA233140.