Similarity of Biological Information Captured by [ 68 ]Ga-PSMA-11 PET and ASL Perfusion MRI in Glioblastoma

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ABSTRACT BACKGROUND AND PURPOSE: To further elucidate the potential biological mechanisms underlying the uptake of PSMA-targeted radioligands in glioblastoma (GBM) and to clarify the value of prostate-specific membrane antigen (PSMA) PET in characterizing the spatial heterogeneity of GBM microvascular distribution, this study aims to investigate the relationship between 68Ga-PSMA-11 PET and arterial spin-labeling (ASL) perfusion imaging, as well as the correlation between PSMA tracer uptake and immunohistochemical microvascular indices. MATERIALS AND METHODS: Twenty-six patients with newly diagnosed or recurrent GBM who underwent conventional MRI, ASL and PSMA PET were prospectively enrolled. We investigated the correlation between the semi-quantitative parameters of ASL and PSMA PET. Spatial similarity and overlap between tumor volumes delineated by contrast-enhanced (CE) MRI, ASL, and PSMA PET were evaluated using Dice similarity coefficients (DSC) and overlap volume (OV). Additionally, microvascular density (MVD) values and PSMA expression levels in the tumor tissue samples were assessed using immunohistochemistry, and their correlation with PSMA tracer uptake was analyzed. RESULTS: A total of 28 lesions were found in 26 patients, all of which showed high perfusion, moderate to high tracer uptake, and CE. In 23 lesions (82%), the areas with the highest tracer uptake on PSMA PET were precisely localized to the regions of the highest perfusion on ASL. A strong positive correlation was found between the parameters derived from ASL and PSMA PET (P < 0.001). PSMA PET exhibited moderate to high spatial similarity and overlap with ASL (mean DSC, 0.62 ± 0.17; mean OV, 0.78 ± 0.12), and with CE MRI (mean DSC, 0.65 ± 0.14; mean OV, 0.79 ± 0.15). Furthermore, a positive correlation was observed between PSMA tracer uptake and both MVD and PSMA expression. CONCLUSIONS: Our results highlight the similarity of biological information captured by PSMA PET and ASL perfusion imaging in GBM. The tracer uptake observed in PSMA PET can also reliably reflect the spatial heterogeneity of the microvascular distribution of GBM. These findings provide compelling support for PSMA-targeted radiotherapy as an anti-angiogenic therapeutic strategy for patients with GBM, while also advancing our understanding of the mechanisms underlying PSMA tracer uptake. ABBREVIATIONS: GBM＝ glioblastoma; PSMA＝prostate-specific membrane antigen; ASL = arterial spin-labeling; CE = contrast enhanced; DSC = Dice similarity coefficients; OV = overlap volume; MVD = microvascular density; TBR = tumor-to-background ratio

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