Change of glucometabolic activity per PSMA expression predicts survival in mCRPC patients non-responding to PSMA radioligand therapy: introducing a novel dual imaging biomarker

Caroline Burgard; Jakob Engler; Arne Blickle; Mark Bartholomä; Stephan Maus; Andrea Schaefer-Schuler; Fadi Khreish; Samer Ezziddin; Florian Rosar

doi:10.3389/fmed.2023.1339160

Change of glucometabolic activity per PSMA expression predicts survival in mCRPC patients non-responding to PSMA radioligand therapy: introducing a novel dual imaging biomarker

Front Med (Lausanne). 2024 Jan 17:10:1339160. doi: 10.3389/fmed.2023.1339160. eCollection 2023.

Authors

Caroline Burgard^#¹, Jakob Engler¹, Arne Blickle¹, Mark Bartholomä¹, Stephan Maus¹, Andrea Schaefer-Schuler¹, Fadi Khreish¹, Samer Ezziddin¹, Florian Rosar¹

Affiliation

¹ Department of Nuclear Medicine, Saarland University-Medical Center, Homburg, Germany.

^# Contributed equally.

Abstract

Purpose: The value of [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) PET/CT in monitoring prostate-specific membrane antigen (PSMA) targeted radioligand therapy (RLT) is still unclear. The aim of this study was to identify appropriate prognostic dynamic parameters derived from baseline and follow-up [¹⁸F]FDG and dual [¹⁸F]FDG/[⁶⁸Ga]Ga-PSMA-11 PET/CT for monitoring early non-responding mCRPC patients undergoing PSMA-RLT.

Methods: Twenty-three mCRPC patients of a prospective registry (NCT04833517), who were treated with [¹⁷⁷Lu]Lu-PSMA-617 RLT and classified as early non-responders were included in this study. All patients received dual PET/CT imaging with [¹⁸F]FDG and [⁶⁸Ga]Ga-PSMA-11 at baseline and after median two cycles of RLT. We tested potential biomarkers representing the "change of glucometabolic activity (cGA)" and "change of glucometabolic activity in relation to PSMA expression (cGAP)" composed of established parameters on [¹⁸F]FDG PET/CT as SUVmax, cumulative SUV of five lesions (SUV5), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) and its corresponding parameters on [⁶⁸Ga]Ga-PSMA-11 PET/CT, respectively, for association with overall survival (OS).

Results: Kaplan-Meier analyses showed no significant association with OS for each tested cGA (cGA_SUVmaxp = 0.904, cGA_SUV5, p = 0.747 cGA_MTVp = 0.682 and cGA_TLGp = 0.700), likewise the dual imaging biomarkers cGAP_SUVmax (p = 0.136), cGAP_SUV5 (p = 0.097), and cGAP_TV (p = 0.113) failed significance. In contrast, cGAP_TL, which is based on TLG and total lesion PSMA (TLP) showed a significant association with OS (p = 0.004). Low cGAP_TL (cut-off 0.7) was associated with significant longer survival (17.6 vs. 12.9 months).

Conclusion: The novel biomarker cGAP_TL, which represents the temporal change of whole-body TLG normalized by TLP, predicts overall survival in the challenging cohort of patients non-responding to PSMA-RLT.

Keywords: PET/CT; PSMA—prostate-specific membrane antigen; dual imaging; prostate cancer; radioligand therapy.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.