Expression of glutamate carboxypeptidase II in the glial tumor recurrence evaluated in vivo using radionuclide imaging

Abstract

Glutamate carboxypeptidase II (GCP), also known as prostate specific membrane antigen (PSMA) has been found to be expressed in glioma vasculature in in-vitro studies. GCP expression can be traced with the use of [68Ga]Ga-PSMA-11 PET/CT used routinely for prostate cancer imaging. The aim of this paper was to analyze GCP expression in the recurrent glial tumors in vivo. 34 patients (pts.) aged 44.5 ± 10.3 years with suspicion of recurrence of histologically confirmed glioma grade III (6 pts.) and grade IV (28 pts.) were included in the study. All patients underwent contrast-enhanced MR and [68Ga]Ga-PSMA-11 PET/CT. No radiopharmaceutical-related adverse events were noted. PET/CT was positive in all the areas suspected for recurrence at MR in all the patients. The recurrence was confirmed by histopathological examinations or follow-up imaging in all cases. The images showed a very low background activity of the normal brain. Median maximal standard uptake value (SUVmax) of the tumors was 6.5 (range 0.9–15.6) and mean standard uptake value (SUVmean) was 3.5 (range 0.9–7.5). Target-to-background (TBR) ratios varied between 15 and 1400 with a median of 152. Target-to-liver background ratios (TLR) ranged from 0.2 to 2.6, the median TLR was 1.3. No significant difference of the measured parameters was found between the subgroups according to the glioma grade. High GCP expression in the recurrent glioma was demonstrated in-vivo with the use of [68Ga]Ga-PSMA-11 PET/CT. As the treatment options in recurrent glioma are limited, this observation may open new therapeutic perspectives with the use of radiolabeled agents targeting the GCP.

Diagnostic Accuracy of PET/CT or PET/MRI Using PSMA-Targeting Radiopharmaceuticals in High-Grade Gliomas: A Systematic Review and a Bivariate Meta-Analysis

“…Overall, 209 records were identified and screened through the comprehensive literature search described above. Taking into account predefined eligibility criteria, these 209 records were assessed for eligibility and 201 records were excluded (178 as not in the field of interest, 6 as reviews, editorials, or letters, and 17 as case reports); 8 remaining articles were judged as eligible for inclusion in the systematic review (qualitative synthesis) after full-text assessment [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. No additional studies were eligible for inclusion after screening the references of these articles.…”

“…No additional studies were eligible for inclusion after screening the references of these articles. Six out of eight articles were included in the meta-analysis (quantitative synthesis) [ 20 , 21 , 22 , 23 , 25 , 26 ]; two studies included in the systematic review were excluded from the meta-analysis [ 24 , 27 ] due to possible partial patient data overlap with other studies of the same research group. Figure 1 summarizes the study selection process.…”

“…Contrast-enhanced MRI was used for comparison in all the included studies. Only some studies reported the use of functional MRI sequences [ 20 , 21 , 24 , 26 ].…”

“…Diagnostic accuracy data of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG patients for each study are listed in Table 4 . Overall, the index test has demonstrated an excellent diagnostic performance in detecting HGG in all studies included in the systematic review, both on a per patient- and on a per lesion-based analysis and in different clinical settings (at initial diagnosis and in the suspicious recurrence after treatment) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Moreover, PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals was very useful in detecting multifocal disease in HGG patients [ 20 , 21 , 23 ].…”

“…Regarding toxicity and safety, the injection of PSMA-targeting radiopharmaceuticals was well tolerated, without any adverse event recorded [ 20 , 24 ]. The image quality of PET with PSMA-targeting radiopharmaceuticals was judged adequate [ 22 ] and interpretation of the images was very easy due to the absence of physiological radiopharmaceutical uptake in the normal brain parenchyma, without ambiguity in deciding whether the scan was positive or negative [ 26 ].…”