Purpose Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRP-R) are expressed in prostate cancer and can be targeted with radiolabeled inhibitors and antagonists. Their performances for the initial characterization of prostatic tumors have been barely evaluated but never compared. We aimed to gather comparative preclinical data of the role of PSMA and GRP-R targeting in prostate cancer. Procedures We retrospectively studied 20 frozen prostatectomy samples with various metastatic risks of the D’Amico classification. Tissue samples were investigated by tissular microimaging using the radiolabeled PSMA inhibitor 111 In-PSMA-617 and the radiolabeled GRP-R antagonist 111 In-RM2. Bindings of the two radiopharmaceuticals were compared to histology and clinico-biological data (Gleason score, PSA values, metastatic risks). Results Binding of 111 In-PSMA-617 was high whatever the metastatic risk ( p = 0.665), Gleason score ( p = 0.555), or PSA value ( p = 0.404) while 111 In-RM2 exhibited a significantly higher binding in the low metastatic risk group ( p = 0.046), in the low PSA value group ( p = 0.001), and in samples with Gleason 6 score ( p = 0.006). Conclusion PSMA and GRP-R based imaging might have complementary performances for the initial characterization of prostatic tumors. Prospective clinical studies comparing the two tracers in this setting are needed.

The imaging of Prostate-Specific Membrane Antigen (PSMA) is now widely used at the initial staging of prostate cancers in patients with a high metastatic risk. However, its ability to detect low-grade tumor lesions is not optimal. Methods: First, we prospectively performed neurotensin receptor-1 (NTS1) IHC in a series of patients receiving both [68Ga]Ga-PSMA-617 and [68Ga]Ga-RM2 before prostatectomy. In this series, PSMA and GRP-R IHC were also available (n = 16). Next, we aimed at confirming the PSMA/GRP-R/NTS1 expression profile by retrospective autoradiography (n = 46) using a specific radiopharmaceuticals study and also aimed to decipher the expression of less-investigated targets such as NTS2, SST2 and CXCR4. Results: In the IHC study, all samples with negative PSMA staining (two patients with ISUP 2 and one with ISUP 3) were strongly positive for NTS1 staining. No samples were negative for all three stains—for PSMA, GRP-R or NTS1. In the autoradiography study, binding of [111In]In-PSMA-617 was high in all ISUP groups. However, some samples did not bind or bound weakly to [111In]In-PSMA-617 (9%). In these cases, binding of [111n]In-JMV 6659 and [111In]In-JMV 7488 towards NTS1 and NTS2 was high. Conclusions: Targeting PSMA and NTS1/NTS2 could allow for the detection of all intraprostatic lesions.

68Ga-labeled prostate-specific membrane antigen inhibitors and 68Ga-labeled gastrin-releasing peptide receptor antagonists showed interesting results for staging biochemically recurrent prostate cancer. In this case, 68Ga–prostate-specific membrane antigen-617 PET/CT, 68Ga-RM2 PET/CT, and 18F-choline PET/CT were performed in a patient (66-year-old man, prostate-specific antigen = 6.7 ng/mL) with biopsy-proven Gleason 9 (5 + 4) prostate cancer, candidate for radical prostatectomy and lymph node dissection.