68Ga–Prostate-Specific Membrane Antigen-11 PET/CT

Abstract

Background Glioblastoma multiforme (GBM) is the most common and most aggressive primary tumor of the brain. After initial therapy and total resection of GBM, 80% to 90% of recurrences occur at the surgical margins. Currently, limited data are available in the literature on the possible use of 68Ga–prostate-specific membrane antigen (PSMA-11) for diagnosis of recurrence in GBM patients. The aim was to assess the feasibility and potential of 68Ga-PSMA-11 PET/CT as a diagnostic procedure in patients with histologically confirmed of GBM and suspected recurrent disease on MRI. Results No radiopharmaceutical-related adverse events were noted. Characterization of recurrent disease with MRI included T2-weighted fast spin-echo images, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences, and gadolinium enhanced T1-weighted images. Visual interpretation of PET showed increased accumulation of 68Ga-PSMA-11 in recurrent lesion detected by T1 contrast enhanced and diffusion-weighted imaging images in all patients with a median SUVmax of the tumor of 6.5 and an SUVmean of 3.5. The median tumor-to-background brain ratio and tumor-to-liver ratio obtained from 68Ga-PSMA-11 PET/CT were 96.7 and 0.8, respectively. Conclusions The extremely low background uptake in normal brain tissue and consequently high tumor-to-brain ratio make 68Ga-PSMA-11 PET/CT highly promising for diagnosis of recurrent disease in GBM patients. Although PSMA expression in recurrent GBM also opens a potential way for targeted peptide therapy with α/β-emitters as well as for prediction of treatment with antiangiogenic agents, the low tumor-to-liver ratio observed in the majority of patients in this study suggests a limited role of radiolabeled PSMA ligands for targeted radionuclide therapy of recurrent GBM.

Tumor uptake in glioblastoma multiforme after IV injection of [177Lu]Lu-PSMA-617

“…Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with limited treatment options in case of recurrence. Prostate-specific membrane antigen (PSMA) expression was demonstrated in microvascular endothelium of GBM and in vivo confirmed by [ 68 Ga]Ga-PSMA-11 PET/CT in primary as well in recurrence tumor [1][2][3][4]. This knowledge opens a new way for targeted, PSMA-based treatment.…”

Neuroimaging Studies Evaluating Effective Therapies for High-Grade Glioma

“…This result confirms the higher tumour specificity of PSMA compared to FET and it suggests that, in patients with positive tumour uptake, 68 Ga-PSMA-617 has a greater clinical potential than 18 F-FET and 18 F-FDG as a tracer for the visualisation of recurrent tumour lesions and for secondary treatment planning. It is worth noting that this observation not only is in agreement with the observations reported in recent studies of recurrent GBM patients, 321,322,326 but also adds value to the literature of case studies reporting the value of 68 Ga-PSMA as a better PET tracer than FDG for the diagnosis, monitoring and treatment planning for primary GBM lesions. 319,331 The results obtained with the mirror-image method were validated by using a second method for the selection of the background activity reference in the contralateral normal brain.…”

“…330 The values of PSMA TBRmean and TBRmax are within the range of values previously determined with the 68 Ga-PSMA-11 tracer by Sasikumar et al 321,322 (median TBRmax = 14.4,; n = 9), but much lower than the values recently determined by Kunikowska et al 326 (median TBRmax = 96.7,n = 15). The lower values obtained in the present study compared to those reported in the study published by Kunikowska et al 326 might be explained both by the different method for background activity region selection and, most importantly, by the slower tumour accumulation of 68 Ga-PSMA-617 compared to 68 Ga-PSMA-11. 323 The lack of reported TBRmean values in previously published studies limits a more thorough comparison, given that this parameter is considered more indicative than TBRmax.…”

“…FET SUVmax values of 2.8 or above confirm the presence of recurrent tumour in the reported five patients, given the previously reported cut-off threshold of SUVmax = 2.2 for optimal differential diagnosis of tumour recurrence. 24,25 The values of PSMA SUVmean and SUVmax observed in this small cohort of patients are within the range of values previously reported by Kunikowska et al 326 and by Sasikumar et al 321 for 68 Ga-PSMA-11 uptake in recurrent GBM patients.…”

“…The value of TLR commonly used to stratify patients for PSMA targeted-radiotherapy is TLR > 1.5. 326 In their study, Kunikowska et al 326 postulated a potential unsuitability of PSMA-based targeted radiotherapies in recurrent GBM patients, due to the low median TLR observed in their patient cohort (i.e. 0.8, range: 0.6-1.8).…”