P09.05.A DOSIMETRY AND IMMUNOHISTOCHEMISTRY STUDY TO ESTABLISH RADIOLABELLED PSMA AS A POTENTIAL THERANOSTIC TARGET IN GLIOMA TREATMENT
Authors: Benger M , Krokos G , Daga K , Marchi F , Jeljeli S , Livieratos L , Bodi I , Rosekilly J , Lavrador J , Kinsella S , Marsden P , Gillett C , Blower P , Brazil L , Ashkan K , Cook G , Hammers A , Booth T C 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma is an incurable cancer with a median survival of 15 months with standard treatment. New targeted therapies are desperately needed. Recent studies have shown prostate-specific membrane antigen (PSMA) expression within glioblastoma endothelium. Visualising this expression using PSMA-targeted PET MRI may provide functional information beyond that currently possible with MRI, as well as providing an avenue for PSMA-targeted radioligand therapy, which has demonstrated safety and efficacy in prostate cancer. We aimed to: 1) Establish kinetics and tumour dosimetry of a PSMA-targeted ligand using PET-MRI combined with multimodal MRI 2) Co-localise the SUVs of different volumes of interest on PET MRI with PSMA immunohistochemistry (IHC) 3) Assess the potential of PSMA as a radioligand target.

MATERIAL AND METHODS
Three glioblastoma patients underwent a 4.5h dynamic scan with injection of [68Ga]PSMA (t=0) on a Siemens PET-MR scanner (mMR). Based on tracer kinetics, a static 15min scan was reconstructed at 60-75min post-injection to assess tracer uptake and tumour-to-background ratio (TBR). Anatomical and functional MR images were acquired during the first 75min acquisition. Tumour regions were delineated on the coregistered 15min static PET images and gadolinium-enhanced T1-weighted MR sequence. Tumour dosimetry calculations were performed on Olinda 1.1. Multiple regions demonstrating either agreement or discordance between [68Ga]PSMA uptake and gadolinium enhancement were targeted for biopsy and PSMA IHC.

RESULTS
For all patients and in all tumour regions, [68Ga]PSMA uptake increased up to ~80min after which it remained constant even at 4h post-injection. Although [68Ga]PSMA and gadolinium demonstrated an overlapping distribution within each tumour, [68Ga]PSMA uptake was fairly heterogenous, whilst gadolinium enhancement was relatively uniform. We showed the relationship between [68Ga]PSMA, IHC, and perfusion and permeability MR parameters. Notably, there were several regions that exhibited high [68Ga]PSMA uptake without corresponding gadolinium enhancement in the tumour area (SUVmax=4.5). Overall, moderate tumour tracer uptake was noted with SUVmax 4.2-5.0, resulting in a high TBR (30-34). [68Ga]PSMA delivered a dose of ~0.01 mGy/MBq which corresponds to 0.38-0.49 MGy/MBq when extrapolated to [177Lu]PSMA, comparable to dose delivered in radioligand therapy for prostate cancer.

CONCLUSION
Patients with glioblastoma exhibited moderate [68Ga]PSMA tumour uptake, broadly overlapping with regions of gadolinium enhancement. For the first time, we demonstrate high [68Ga]PSMA uptake in non-enhancing regions of tumour, highlighting the potential of this technique to identify aggressive/transforming regions of tumour invisible to conventional MRI. Kinetic analysis shows the potential for theranostic targeting with [177Lu]PSMA.