Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R

SIMPLE SUMMARY: The accurate assessment of the aggressiveness and localization of primary prostate cancer lesions are essential for treatment decision making. Around 15% of lesions are missed by PSMA Positron-Emission tomography/computed Tomography (PET/CT). The aim of our study was to investigate the potential of novel surface markers to detect PSMA-negative lesions using immunohistochemistry and autoradiography techniques. Our work demonstrates that targeting both PSMA and neurotensin receptors might detect all intra-prostatic lesions. This new finding has implications for the future theranostics of primary prostate cancer. ABSTRACT: 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 (NTS(1)) IHC in a series of patients receiving both [(68)Ga]Ga-PSMA-617 and [(68)Ga]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/NTS(1) 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 NTS(2), SST(2) 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 NTS(1) staining. No samples were negative for all three stains—for PSMA, GRP-R or NTS(1). In the autoradiography study, binding of [(111)In]In-PSMA-617 was high in all ISUP groups. However, some samples did not bind or bound weakly to [(111)In]In-PSMA-617 (9%). In these cases, binding of [(111)n]In-JMV 6659 and [(111)In]In-JMV 7488 towards NTS(1) and NTS(2) was high. Conclusions: Targeting PSMA and NTS(1)/NTS(2) could allow for the detection of all intraprostatic lesions.