PSMA PET/MR is a New Imaging Option for Identifying Glioma Recurrence
and Predicting Prognosis
Authors: Xiong Min , Chen Zhenghe , Zhou Chao , Yang Xiaochun , Hu Wanming , Jiang Yongluo , Zheng Rongliang , Fan Wei , Mou Yonggao , Lin Xiaoping 
Published: May 2023

Background:
Glioma is characterized by a high recurrence rate, while the results of the
traditional imaging methods (including magnetic resonance imaging, MRI) to distinguish recurrence
from treatment-related changes (TRCs) are poor. Prostate-specific membrane antigen
(PSMA) (US10815200B2, Deutsches Krebsforschungszentrum, German Cancer Research Center)
is a type II transmembrane glycoprotein overexpressed in glioma vascular endothelium, and it is a
promising target for imaging and therapy.

Objective:
The study aimed to assess the performance of PSMA positron emission tomography/
magnetic resonance (PET/MR) for diagnosing recurrence and predicting prognosis in glioma
patients.

Materials and Methods:
Patients suspected of glioma recurrence who underwent 18F-PSMA-1007
PET/MR were prospectively enrolled. Eight metabolic parameters and fifteen texture features of
the lesion were extracted from PSMA PET/MR. The ability of PSMA PET/MR to diagnose glioma
recurrence was investigated and compared with conventional MRI. The diagnostic agreement
was assessed using Cohen κ scores and the predictive parameters of PSMA PET/MR were obtained.
Kaplan-Meier method and Cox proportional hazard model were used to analyze recurrence-
free survival (RFS) and overall survival (OS). Finally, the expression of PSMA was analyzed
by immunohistochemistry (IHC).

Results:
Nineteen patients with a mean age of 48.11±15.72 were assessed. The maximum tumorto-
parotid ratio (TPRmax) and texture features extracted from PET and T1-weighted contrast enhancement
(T1-CE) MR showed differences between recurrence and TRCs (all p <0.05). PSMA
PET/MR and conventional MRI exhibited comparable power in diagnosing recurrence with specificity
and PPV of 100%. The interobserver concordance was fair between the two modalities (κ = 0.542,
p = 0.072). The optimal cutoffs of metabolic parameters, including standardized uptake value (SUV,
SUVmax, SUVmean, and SUVpeak) and TPRmax for predicting recurrence were 3.35, 1.73, 1.99, and 0.17
respectively, with the area under the curve (AUC) ranging from 0.767 to 0.817 (all p <0.05). In grade
4 glioblastoma (GBM) patients, SUVmax, SUVmean, SUVpeak, TBRmax, TBRmean, and TPRmax showed
improved performance of AUC (0.833-0.867, p <0.05). Patients with SUVmax, SUVmean, or SUVpeak
more than the cutoff value had significantly shorter RFS (all p <0.05). In addition, patients with SUVmean,
SUVpeak, or TPRmax more than the cutoff value had significantly shorter OS (all p <0.05).
PSMA expression of glioma vascular endothelium was observed in ten (10/11, 90.9%) patients with
moderate-to-high levels in all GBM cases (n = 6/6, 100%).

Conclusion:
This primitive study shows multiparameter PSMA PET/MR to be useful in identifying
glioma (especially GBM) recurrence by providing excellent tumor background comparison,
tumor heterogeneity, recurrence prediction and prognosis information, although it did not improve
the diagnostic performance compared to conventional MRI. Further and larger studies are required
to define its potential clinical application in this setting.