Abstract
INTRODUCTION: Radioligand therapies represent an area of increasing interest in brain tumors. Prostate-specific membrane antigen (PSMA)-targeted treatment by [(177)Lu]Lu-PSMA-617 is approved in prostate cancer, and immunohistochemical studies have shown PSMA expression in brain tumors including glioblastoma. However, data on spatial distribution and volume similarities with amino acid PET and contrast-enhanced MRI are lacking. METHODS: Patients with glioma or brain metastasis of prostate cancer who underwent either [(18)F]PSMA-1007 or [(68)Ga]Ga-PSMA-11 PET were included. PET uptake and volumes were measured, contrast-enhancing volumes in MRI were segmented, and Dice coefficients and volume overlaps were calculated to evaluate volume similarities. Two patients were treated with [(177)Lu]Lu-PSMA-617 within a compassionate use program. RESULTS: In total, 15 patients were included (9 [60.0%] glioblastoma, 4 [26.7%] IDH-mutant glioma, 2 [13.3%] prostate cancer brain metastasis [BM]). PET showed highest uptake values in prostate cancer BM (median: 2.5 [range: 2.1-2.8]) followed by glioblastoma (1.8 [1.0-5.3]) and IDH-mutant glioma (1.0 [0.1-2.3]; p=0.032). The ranges of overlaps and volume similarities were high, suggesting considerable inter-individual variability. Overall, PSMA PET-positive volumes were smaller (PSMA+: 1.53 mL [0.00-59.30]) than FET-positive volumes (PSMA+: 4.72 mL [0.00-115.00], p=0.001) but had similar size compared to contrast-enhancing MRI volumes (CE+: 1.73 mL [0.00-30.70], p=1.000). Of segmented volumes, similar portions of PSMA+ volumes were within and outside CE+ volumes (glioblastoma: 17% vs. 17.9%; IDH-mutant glioma: 3.5% vs. 3.9%). Median Dice coefficients were 0.076 (0.016-0.835) for PSMA+/FET+ and 0.246 (0.000-0.778) for CE+/PSMA+. In the two patients with glioma receiving [(177)Lu]Lu-PSMA-617 treatment, transient disease stabilization was observed. CONCLUSION: PSMA PET shows target expression in brain tumors. PSMA+ volumes are smaller than metabolically active tumor as determined by amino acid PET but similar to CE+ volumes, indicating potential synergism of PSMA-targeted radioligand therapies with strategies to open the blood-brain barrier.