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

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

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1339160

DOI=10.3389/fmed.2023.1339160

ISSN=2296-858X

ABSTRACT=<sec id="sec1"><title>Purpose</title><p>The value of [<sup>18</sup>F]fluorodeoxyglucose ([<sup>18</sup>F]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 [<sup>18</sup>F]FDG and dual [<sup>18</sup>F]FDG/[<sup>68</sup>Ga]Ga-PSMA-11 PET/CT for monitoring early non-responding mCRPC patients undergoing PSMA-RLT.</p></sec><sec id="sec2"><title>Methods</title><p>Twenty-three mCRPC patients of a prospective registry (NCT04833517), who were treated with [<sup>177</sup>Lu]Lu-PSMA-617 RLT and classified as early non-responders were included in this study. All patients received dual PET/CT imaging with [<sup>18</sup>F]FDG and [<sup>68</sup>Ga]Ga-PSMA-11 at baseline and after median two cycles of RLT. We tested potential biomarkers representing the “<italic>change of glucometabolic activity (cGA)</italic>” and “<italic>change of glucometabolic activity in relation to PSMA expression (cGAP)</italic>” composed of established parameters on [<sup>18</sup>F]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 [<sup>68</sup>Ga]Ga-PSMA-11 PET/CT, respectively, for association with overall survival (OS).</p></sec><sec id="sec3"><title>Results</title><p>Kaplan–Meier analyses showed no significant association with OS for each tested cGA (cGA<sub>SUVmax</sub><italic>p</italic> = 0.904, cGA<sub>SUV5</sub>, <italic>p</italic> = 0.747 cGA<sub>MTV</sub><italic>p</italic> = 0.682 and cGA<sub>TLG</sub><italic>p</italic> = 0.700), likewise the dual imaging biomarkers cGAP<sub>SUVmax</sub> (<italic>p</italic> = 0.136), cGAP<sub>SUV5</sub> (<italic>p</italic> = 0.097), and cGAP<sub>TV</sub> (<italic>p</italic> = 0.113) failed significance. In contrast, cGAP<sub>TL</sub>, which is based on TLG and total lesion PSMA (TLP) showed a significant association with OS (<italic>p</italic> = 0.004). Low cGAP<sub>TL</sub> (cut-off 0.7) was associated with significant longer survival (17.6 vs. 12.9 months).</p></sec><sec id="sec4"><title>Conclusion</title><p>The novel biomarker cGAP<sub>TL</sub>, 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.</p></sec>