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. 2025 Apr 9;15(1):38.
doi: 10.1186/s13550-025-01232-8.

Prostate-specific membrane antigen (PSMA) expression in primary and metastatic renal cell cancer (UroCCR-65 study)

Salma Binzaqr  1 , David Kryza  2   3 , Anne-Laure Giraudet  2 , Jean Christophe Bernhard  4   5 , Marine Gross-Goupil  4 , Mokrane Yacoub  6 , Gaelle Margue  4   5 , Elif Hindié  1   7   8 , Clément Morgat  9   10
Affiliations

Prostate-specific membrane antigen (PSMA) expression in primary and metastatic renal cell cancer (UroCCR-65 study)

Salma Binzaqr et al. EJNMMI Res. .

Abstract

Background: Prostate-specific membrane antigen (PSMA) has been shown to be overexpressed in the neo-vasculature of renal cancers. However, studies investigating the pattern of PSMA expression in primary RCC and RCC metastases according to metastatic sites are rare. 44 frozen samples of RCC, 19 primaries (9 clear cell (cc) RCC, 7 papillary (pap) RCC, and 3 chromophobe (ch) RCC) and 25 (24 samples have ccRCC histology and one is unclassified) unpaired metastases (8 from adrenals, 8 from bones, 2 from lungs, 2 from liver and 5 others (1 lymph node, 1 pancreas, 1 brain, 1 gallbladder and 1 muscle)), were available from the UroCCR project (NCT03293563). PSMA expression was assessed by autoradiography using [177Lu]Lu-PSMA-617 as binding agent and the specific binding (total binding-non-specific binding) was calculated and expressed as a percentage of total binding. A patient suffering from metastatic ccRCC was also administered [68Ga]Ga-PSMA-11 to evaluate PSMA expression.

Results: The mean specific binding was 28.9 ± 40.4% for primary renal cancer and 65.0 ± 38.9% for metastasis. Regarding histology, high PSMA expression was depicted in 33.3% of ccRCC, 33.3% of chRCC and 57.1% of papRCC. PSMA was more frequently expressed in primary samples of papRCC histology with renal capsule invasion (p = 0.0286). A higher PSMA-specific binding and a higher number of samples with high PSMA-expression were depicted in metastatic samples. Bone metastasis showed lower binding than other metastatic sites combined (p = 0.0005). The patient suffering from metastatic ccRCC showed high [68Ga]Ga-PSMA-11 uptake on known distant metastases and additional site uncovered.

Conclusion: PSMA showed high expression in metastases of ccRCC.

Clinical trial registration: NCT, NCT03293563, prospectively registered September 20, 2017, http://www.

Clinicaltrials: gov .

Keywords: Clear cell RCC; Kidney cancer; Metastatic RCC; PSMA; Primary RCC.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The UroCCR project (NCT03293563), which is IRB-approved and has the CNIL authorization number DR-2013-206. The UroCCR database received approval from Comité de Protection des Personnes Sud-Ouest et Outre-mer III (DC 2012/108) and favorable opinion of the Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé (CCTIRS). Consent for publication: Written informed consent was obtained for publication. Competing interests: The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
(A) HES staining of an adrenal metastasis sample from ccRCC. (B) [177Lu]Lu-PSMA-617 autoradiography to the same sample, showing high binding. The unit of the scale bar is cpm/mm²
Fig. 2
Fig. 2
PSMA expression according to metastatic sites
Fig. 3
Fig. 3
Patient was imaged with [68Ga]Ga-PSMA-11 PET before therapy with [177Lu]Lu-PSMA-1 within the frame of the «PRaDR» trial. The patient was known to have distant metastases at multiple sites, including right adrenal gland, head of the pancreas, lung, hilar lymph nodes, as well as peritoneal lesions, the largest being localized in the left hypochondrium. All these lesions presented with an intense PSMA expression as shown on the Maximum Intensity Projection (MIP) of the [68Ga]Ga-PSMA PET acquisition (103 MBq of [68Ga]Ga-PSMA-11; 1.3 min/bed acquisition on the Philips VEREOS) (a). An intense focal uptake, corresponding to an osteolytic bone lesion of the left femur on the CT component of the PET/CT (b) and the PET/CT fused image (c), was additionally uncovered
See this image and copyright information in PMC

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