PSMA radioligand uptake correlates with PSMA expression in high-grade glioma and brain metastasis: insights from a prospective PET-MRI guided multiregional biopsy study
Ilanah J. Pruis, Vera van Dis, Sybren L. N. Maas, Rutger K. Balvers, Thierry P. P. van den Bosch, Marcel Segbers, Sophie E. M. Veldhuijzen van Zanten
Abstract
Abstract Purpose Prostate-specific membrane antigen (PSMA) is a potential target for radioligand therapy (RLT) in neuro-oncology. This study investigates the direct relation between [ 68 Ga]Ga-PSMA-11 uptake on PET and PSMA expression in the tumour micro-environment of high-grade glioma (HGG) and brain metastasis (BM). Methods Twelve patients with HGG (glioblastoma n = 6, oligodendroglioma n = 1), or BM (lung- n = 4, breast cancer n = 1), underwent PET-MRI after intravenous [ 68 Ga]Ga-PSMA-11 injection (1.5 MBq/kg), followed by image-guided biopsy sampling during (re-)resection surgery. Multiple samples (median n = 3/patient, n = 23 HGG/ n = 20 BM) from locations of low and high [ 68 Ga]Ga-PSMA-11 uptake were analysed for PSMA expression in vasculature and non-vascular structures using morphology and immunohistochemistry. Results All patients showed [ 68 Ga]Ga-PSMA-11 uptake in tumour ( SUVmax median, range: 10.5, 4.7–19.8). Strong PSMA expression was found in tumour microvasculature (14/23, 61% in HGG, 13/20, 65% in BM). Tumour cell PSMA expression was found in a subset of HGG (10/23; of which strong in 8/10) and BM (3/20; none of which showed strong expression). Strong PSMA expression was also found on non-malignant glial cells in tumour. PSMA expression in healthy brain control samples was negligible. In HGG, a significant correlation existed between [ 68 Ga]Ga-PSMA-11 uptake and PSMA expression in tumour microvasculature (r = 0.487, P < 0.01), but not tumour cells. Conclusion PSMA expression in brain tumours is predominately vascular, which likely explains why microvascular (rather than tumour cell) PSMA expression correlates with [ 68 Ga]Ga-PSMA-11 uptake in HGG. This neovascular expression is crucial information for future PSMA-based RLT studies, as alpha-emitters may not sufficiently target tumour DNA. NCT05798273; date of registration: 1/9/2020.