Can PSMA PET Detect Intratumour Heterogeneity in Histological PSMA Expression of Primary Prostate Cancer? Analysis of [Ga]Ga-PSMA-11 and [F]PSMA-1007

Overview

Journal Eur J Nucl Med Mol Imaging

Date 2025 Jan 17

PMID 39821663

Authors

Philipp Moritz Adrian Waibel

Ievgen Glavynskyi

Tobias Fechter

Michael Mix

Felix Kind

August Sigle

Cordula Annette Jilg

Christian Gratzke

Martin Werner

Oliver Schilling

Peter Bronsert

Martin Thomas Freitag

Constantinos Zamboglou

Anca-Ligia Grosu

Simon Konrad Benedikt Spohn

Affiliations

Soon will be listed here.

Abstract

Purpose: Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [Ga]Ga-PSMA-11 or [F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression.

Methods: Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled. All patients underwent PSMA PET combined with computer tomography (CT) with either [Ga]Ga-PSMA-11 (cohort I, 20 patients) or [F]PSMA-1007 (cohort II, 15 patients) followed by radical prostatectomy. Specimens were scanned by ex-vivo CT and histologically prepared. On digitized whole-mount prostate sections, PCa areas with different morphologies were manually defined and H-Score of immunohistochemical PSMA expression was calculated with assistance by artificial intelligence (AI). PCa areas with similar H-Score were unified in segmentation on ex-vivo CT. After co-registration on PSMA PET-CT, Spearman's coefficients of PSMA expression to mean and maximum standardized uptake value (SUV and SUV) were calculated. Furthermore, the agreement of the co-registered tumour areas to gross tumour volume (GTV) in PSMA PET was analysed.

Results: Thirty-two patients were included in the final analysis. For histological PCa areas, immunohistochemical PSMA expression correlated significantly to SUV and SUV (p < 0.001, p = 0.001). An approximate linear correlation between H-Score and SUV / SUV was found for tumour areas larger than 400 μm² in histology (p < 0.001). Tumour areas with strong PSMA expression showed a significantly larger overlap to GTV in PSMA PET after co-registration than tumour areas with very low PSMA expression (p < 0.01). No significant differences were found between the two tracer cohorts (p = 0.72).

Conclusion: PSMA PET with both [Ga]Ga-PSMA-11 or [F]PSMA-1007 is able to detect changes in histological PSMA expression within PCa lesions allowing biologically targeted radiotherapy.

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