Dosimetry and immunohistochemistry study to establish radiolabelled prostate-specific membrane antigen (PSMA) as a potential theranostic target in high-grade glioma treatment

Prostate-specific membrane antigen (PSMA) is upregulated in high-grade glioma (HGG). This study aimed, firstly, to establish dosimetry for the radionuclide [68Ga]-PSMA-11 in HGG patients; secondly, to determine theoretical tumour doses for [177Lu]-PSMA, a potential therapeutic radionuclide; thirdly, to assess PSMA immunohistochemistry in targeted intra-operative HGG biopsies. Three HGG patients underwent PET-MRI after injection of 185 MBq [68Ga]-PSMA-11. Targeted intra-operative HGG biopsies were immunostained for PSMA and endothelium (CD34). There was durable, heterogeneous uptake of [ 68Ga]-PSMA-11 with moderate SUVmax (4.2-5.0) and high TBR (60-183). [68Ga]-PSMA-11 delivered a tumour dose of 0.01-0.03 mGy/MBq corresponding to 0.38-1.10 mGy/MBq for [177Lu]-PSMA. PSMA staining was predominantly seen in necrotic/proliferating CD34-positive cells. HGGs exhibited moderate and heterogeneous [68Ga]-PSMA-11 uptake, corresponding to a theoretical [177Lu] tumour dose lower than conventional external beam radiotherapy but within the range used for theranostic treatment in prostate cancer. PSMA staining was most prevalent in regions of tumour with necrotic/proliferating endothelium.