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. 2023 Apr 18;15(8):2345.
doi: 10.3390/cancers15082345.

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

Romain Schollhammer  1   2 , Marie-Laure Quintyn Ranty  3 , Henri de Clermont Gallerande  1   2 , Florine Cavelier  4 , Ibai E Valverde  5 , Delphine Vimont  2 , Elif Hindié  1   2   6 , Clément Morgat  1   2
Affiliations

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

Romain Schollhammer et al. Cancers (Basel). .

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 (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.

Keywords: GRP-R; NTS1; NTS2; PSMA; neuropeptide; neurotensin; prostate cancer.

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Conflict of interest statement

Life Molecular Imaging provided the RM2 precursor and the [natGa]Ga-RM2 reference compound, but had no role in the design, execution, interpretation, or writing of the study. The authors declare no other conflict of interest.

Figures

Figure 1
Figure 1
Example of a prostatic ISUP-2 sample (HES staining in (A)) negative for PSMA (B) and GRP-R (C) immunohistochemistry, but with positive staining for NTS1 immunochemistry (D). Images were taken at 10× magnification.
Figure 2
Figure 2
Comparison of the binding between PSMA, GRP-R, NTS1, NTS2 and SST2-specific radiopharmaceuticals on an ISUP-1 sample. The red line drawing on the HES slice corresponds to the tumor area. Specific binding = 92% for PSMA, 90% for GRP-R, 67% for NTS1, 92% for NTS2 and 47% for SST2. Color scale refers to cps/mm².
Figure 3
Figure 3
Comparison of the binding between PSMA, GRP-R, NTS1, NTS2 and SST2-specific radiopharmaceuticals on an ISUP-5 sample. The red line drawing on HES slice corresponds to the tumor area. Specific binding = 45% for PSMA, 40% for NTS1, 95% for NTS2 and 40% for SST2. Specific binding was not available for GRP-R due to technical issues. Color scale refers to cps/mm².
Figure 4
Figure 4
Comparison between PSMA, GRP-R, NTS1, NTS2 and CXCR4-specific radiopharmaceuticals on an ISUP-5 sample. The red line drawing on HES slice corresponds to the tumor area. PSMA, GRP-R and NTS1 samples showed no uptake on the tumoral area. Contrarily, NTS2, and CXCR4 showed a strong tumor uptake. Specific binding = 0% for PSMA, 0% for GRP-R, 0% for NTS1, 71% for NTS2 and 100% for CXCR4. Color scale refers to cps/mm².
See this image and copyright information in PMC

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