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

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.

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.

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.

Targeting PSMA and NTS₁/NTS₂ could allow for the detection of all intraprostatic lesions.