PSMA radioligand uptake correlates with PSMA expression in high-grade glioma and brain metastasis: insights from a prospective PET-MRI guided multiregional biopsy study.

Purpose: Prostate-specific membrane antigen (PSMA) is a potential target for radioligand therapy (RLT) in neuro-oncology. This study investigates the direct relation between [68Ga]Ga-PSMA-11 uptake on PET and PSMA expression in the tumour micro-environment of high-grade glioma (HGG) and brain metast...

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Published in:European Journal of Nuclear Medicine & Molecular Imaging Vol. 52; no. 13; pp. 4870 - 4882
Main Authors: Pruis, Ilanah J., van Dis, Vera, Maas, Sybren L. N., Balvers, Rutger K., van den Bosch, Thierry P. P., Segbers, Marcel, Veldhuijzen van Zanten, Sophie E. M.
Format: Journal Article
Published: Springer Nature Nov2025
Online Access:View this record in EBSCOhost
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      dt: Nov2025
      vid: 52
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      pub: Springer Nature
      place: New York, New York
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        189136465
        185384252
        10.1007/s00259-025-07338-4
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        atl: PSMA radioligand uptake correlates with PSMA expression in high-grade glioma and brain metastasis: insights from a prospective PET-MRI guided multiregional biopsy study.
      aug:
        au:
          Pruis, Ilanah J.
          van Dis, Vera
          Maas, Sybren L. N.
          Balvers, Rutger K.
          van den Bosch, Thierry P. P.
          Segbers, Marcel
          Veldhuijzen van Zanten, Sophie E. M.
        affil: https://ror.org/018906e22 Department of Radiology and Nuclear Medicine, University Medical Centre Rotterdam, Rotterdam, The Netherlands
      sug:
      ab: Purpose: Prostate-specific membrane antigen (PSMA) is a potential target for radioligand therapy (RLT) in neuro-oncology. This study investigates the direct relation between [68Ga]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 [68Ga]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 [68Ga]Ga-PSMA-11 uptake were analysed for PSMA expression in vasculature and non-vascular structures using morphology and immunohistochemistry. Results: All patients showed [68Ga]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 [68Ga]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 [68Ga]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.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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