[(68)Ga]Ga-PSMA PET/MRI, histological PSMA expression and preliminary experience with [(177)Lu]Lu-PSMA therapy in relapsing high-grade glioma

PURPOSE: High-grade gliomas (HGG) are still associated with a dismal prognosis. Prostate specific membrane antigen (PSMA) is discussed as a theranostic target for PSMA-directed radioligand therapy ([(177)Lu]Lu-PSMA RLT). Here, we report on the correlation of [(68)Ga]Ga-PSMA uptake with histological PSMA expression and on our preliminary experience with [(177)Lu]Lu-PSMA RLT in relapsing HGG. METHODS: Patients with relapsing HGG underwent [(68)Ga]Ga-PSMA PET/MRI to evaluate eligibility for an individualized treatment approach with [(177)Lu]Lu-PSMA. Standard uptake values (SUV) for tumor and liver and respective tumor-to-background ratios (compared to the liver) (TBR) on [(68)Ga]Ga-PSMA PET/MRI were assessed. Eligibility criteria for [(177)Lu]Lu-PSMA therapy were exhaustion of all standard treatment options available and TBR(max)>1.0. In 11 samples, immunohistochemical PSMA expression was determined, quantified using the H-score and correlated with uptake on [(68)Ga]Ga-PSMA PET/MRI. RESULTS: We included 20 patients with a median age of 53 years (IQR 42-57). The median SUV on [(68)Ga]Ga-PSMA PET/MRI was 4.5 (3.7-6.2) for SUV(max) and 1.4 (1.1-1.7) for SUV(mean). The respective TBR was maximum 0.6 (0.4-0.8) and mean 0.3 (0.2-0.4). High TBR(max) correlated with increased endothelial PSMA expression [H-score of 65 (62.5-77.5)]. Three patients (15%) presented a TBR(max)>1.0 and qualified for [(177)Lu]Lu-PSMA RLT. No treatment related toxicity was observed. CONCLUSION: Only a minority of patients with relapsing HGG qualified for [(177)Lu]Lu-PSMA RLT. Our data demonstrates that PSMA expression in the neo-vasculature corresponds to PSMA uptake on [(68)Ga]Ga-PSMA PET/MRI and might be used as a screening tool for patient selection. Future prospective studies need to focus the debate on TBR(max) thresholds as inclusion criteria for PSMA RLT.