# GRPR imaging when the PSMA scan is negative

Source: https://nuclide.cc/opportunities/opp-grpr-psma-negative-prostate/  
Nuclide record `opp-grpr-psma-negative-prostate` (Opportunity). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Prostate cancer imaging and treatment both rely on one protein, PSMA. In a minority of men the tumour does not carry it, and for those men a negative scan is a dead end. A second receptor, GRPR, is the best-studied alternative, and the honest reading of the head-to-head studies is that it finds fewer lesions overall but different ones.

## Summary

PSMA has become the single axis of prostate cancer molecular imaging and radioligand therapy, which means the patient whose tumour does not express it has nowhere to go. The published estimates of how large that group is vary by how it is measured: around 5 to 10% of primary tumours are PSMA-negative on immunohistochemistry and around 10% are negative on PSMA PET despite a high PSA, while a commentary puts the figure at 15 to 25% of metastatic castration-resistant patients whose tumours do not significantly express PSMA.

GRPR is the most clinically mature alternative. 68Ga-RM2 has a completed phase 2/3 imaging trial published in Lancet Oncology in 2024: of 209 men screened, 100 were analysed, and RM2 PET-MRI was positive in 69% against 40% for MRI alone, with no grade 1 or worse events. But the head-to-head studies are not a story of superiority. At Stanford, in 50 patients imaged with both, PSMA-directed tracers found 36 extra lesions in 13 patients while RM2 found 7 extra in 4 patients. In a Chilean mCRPC cohort of 17 patients referred for radioligand therapy, PSMA detected 23% more lesions, though in 4 of 17 the two distributions were comparable. A Bordeaux study found the two discordant in 18.8% of lesions, with RM2 better at low-ISUP tumours and PSMA better at clinically significant ones.

That is the shape of the real opportunity: not a replacement for PSMA PET but a second-look agent for the specific patient in whom PSMA imaging has failed, and a selection test for GRPR-directed therapy. 177Lu-NeoB from Advanced Accelerator Applications has completed phase 1 in NeoRay with a maximum tolerated dose of 9.25 GBq in 17 patients, and 177Lu-RM2 has first-in-human dosimetry in 4 mCRPC patients selected precisely because they had insufficient PSMA expression.

## Fields

- Kind: Opportunity
- Last checked: 2026-09-23
- Also known as: GRPR PET; bombesin receptor imaging
- Tags: unmet need first; prostate; PSMA-negative; second-look imaging

## Sources

- 68Ga-RM2 phase 2/3, Lancet Oncology 2024: https://pubmed.ncbi.nlm.nih.gov/38423030/
- 68Ga-RM2 against PSMA tracers head to head, J Nucl Med 2021: https://pmc.ncbi.nlm.nih.gov/articles/PMC8612333/
- 177Lu-RM2 first-in-human dosimetry in PSMA-insufficient patients: https://pubmed.ncbi.nlm.nih.gov/31482426/
- NCT03872778: NeoRay, 177Lu-NeoB: https://clinicaltrials.gov/study/NCT03872778
- GRPR distribution in cancer, J Nucl Med 2020: https://jnm.snmjournals.org/content/61/6/792

## Connected records

- isotopes: [Gallium-68](https://nuclide.cc/isotopes/ga-68/), [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)
- indications: [Biochemical recurrence of prostate cancer](https://nuclide.cc/indications/prostate-bcr/), [Metastatic castration-resistant prostate cancer](https://nuclide.cc/indications/prostate-mcrpc/)
- technologies: [Peptide-drug & small-molecule-drug conjugates](https://nuclide.cc/technologies/peptide-drug-conjugate/), [PET/CT](https://nuclide.cc/technologies/pet-ct/), [PSMA PET](https://nuclide.cc/technologies/psma-pet/), [Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/)
- targets: [GRPR (gastrin-releasing peptide receptor)](https://nuclide.cc/targets/grpr/), [PSMA](https://nuclide.cc/targets/psma/)

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