Journal
CANCERS
Volume 15, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cancers15082345
Keywords
prostate cancer; neuropeptide; PSMA; GRP-R; NTS1; NTS2; neurotensin
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The accurate assessment of primary prostate cancer lesions is crucial for treatment decision making. PSMA Positron-Emission tomography/computed Tomography (PET/CT) may miss around 15% of lesions. Our study reveals that targeting both PSMA and neurotensin receptors could detect all intraprostatic lesions, which has implications for future theranostics of primary prostate cancer.
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. 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 [Ga-68]Ga-PSMA-617 and [Ga-68]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 [In-111]In-PSMA-617 was high in all ISUP groups. However, some samples did not bind or bound weakly to [In-111]In-PSMA-617 (9%). In these cases, binding of [(111)n]In-JMV 6659 and [In-111]In-JMV 7488 towards NTS1 and NTS2 was high. Conclusions: Targeting PSMA and NTS1/NTS2 could allow for the detection of all intraprostatic lesions.
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