Clinical Nuclear Medicine

To study the association of metabolic features of ¹⁸F-fluorocholine in gliomas with histopathological and molecular parameters, progression-free survival (PFS) and overall survival (OS).

Prospective multicenter and nonrandomized study (Functional and Metabolic Glioma Analysis). Patients underwent a basal ¹⁸F-fluorocholine PET/CT and were included after histological confirmation of glioma. Histological and molecular profile was assessed: grade, Ki-67, isocitrate dehydrogenase status and 1p/19q codeletion. Patients underwent standard treatment after surgery or biopsy, depending on their clinical situation. Overall survival and PFS were obtained after follow-up. After tumor segmentation of PET images, SUV and volume-based variables, sphericity, surface, coefficient of variation, and multilesionality were obtained. Relations of metabolic variables with histological, molecular profile and prognosis were evaluated using Pearson χ² and t test. Receiver operator caracteristic curves were used to obtain the cutoff of PET variables. Survival analysis was performed using Kaplan-Meier and Cox regression analysis.

Forty-five patients were assessed; 38 were diagnosed as having high-grade gliomas. Significant differences of SUV-based variables with isocitrate dehydrogenase status, tumor grade, and Ki-67 were found. Tumor grade, Ki-67, SUVmax, and SUVmean were related to progression. Kaplan-Meier analysis revealed significant associations of SUVmax, SUVmean, and multilesionaly with OS and PFS. SUVmean, sphericity, and multilesionality were independent predictors of OS and PFS in Cox regression analysis.

Metabolic information obtained from ¹⁸F-fluorocholine PET of patients with glioma may be useful in the prediction of tumor biology and patient prognosis.

To retrospectively investigate the uptake of ¹⁸F-fluciclovine on PET/CT in patients with suspected recurrent high-grade glioma (HGG).

Twenty-one patients were included. The standard of truth was histopathologic interpretation if available. When histopathology was not available or rebiopsy did not show signs of malignancy, clinical follow-up including MRI and clinical outcome was considered the standard of truth.

All 21 patients met the reference standard of either histopathologic proof of HGG recurrence (n = 10) or disease progression clinically and with tumor growth corresponding to the primary tumor sites on follow-up MRI (n = 11). Median time from PET/CT to death was 5 months (range, 1–20 months). Median time from primary diagnosis to death was 14.5 months (range, 6 to >400). Average SUVmax of the lesions was 8.3 ± 5.3 (SD) and 0.34 ± 0.13 for normal brain tissue. Median lesion-to-background ratio was 21.6 (range, 3.1–84.4). In 4 patients, ¹⁸F-fluciclovine PET/CT detected small satellite tumors that had not been reported on MR.

The uptake of ¹⁸F-fluciclovine in clinically and/or histopathologically confirmed recurrent HGG is high compared with the uptake reported for other amino acid PET tracers. Because of the high tumor uptake and thus high tracer contrast, small satellite tumors with a diameter below usual reported PET spatial resolution and not reported on MRI were detected in 4 patients. As no patients with confirmed treatment-related changes were included, we cannot as of yet ascertain the ability of ¹⁸F-fluciclovine PET to discriminate between recurrent HGG and treatment-related changes, for example, pseudoprogression and radionecrosis.

Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein, which is not only overexpressed in prostate cancers but also in variety of solid tumors including glioblastoma multiforme. The aim of the present study was to demonstrate PSMA expression in gliomas using ⁶⁸Ga-PSMA-HBED-CC(PSMA 11) PET/CT.

Ten patients with initially MRI suspected and eventually histopathologically proven gliomas [8 males (age range 30–73 yr; mean age 51.8 yr); 2 females aged 39 and 55 years] were subjected preoperatively to regional brain PET scan with ⁶⁸Ga-PSMA-11 and ¹⁸F-FDG PET/CT. Final histopathology of brain lesions, their MIB-1 proliferation index (MIB-1 PI) were compared with PSMA and FDG PET findings.

FDG PET/CT showed distinct FDG uptake in high-grade gliomas, whereas low-grade gliomas were non-FDG-avid amidst physiological tracer uptake. In vivo PSMA expression was seen in all patients with glioma. Of these, the 7 patients of glioblastoma harboring 8 lesions showed significantly higher PSMA expression than those with low-grade gliomas, average SUVmax being 16.93 and 2.93, respectively. Similarly, average tumor-to-background ratios (13.95 and 3.42, respectively) and MIB-1 PI (17.31 and 3.3, respectively) were substantially more in high-grade versus low-grade gliomas.

The results of this pilot study show that ⁶⁸Ga-HBED-CC-PSMA PET/CT can be used to characterize the PSMA expression in gliomas, high-grade ones demonstrating higher SUVmax, MIB-1 PI tumor-to-background ratio than the low-grade ones. With these results as basis, certain patients may benefit from potential PSMA-targeted radionuclide therapy.

This pilot study aimed to evaluate the amino acid tracer ¹⁸F-FACBC with simultaneous PET/MRI in diagnostic assessment and neurosurgery of gliomas.

Eleven patients with suspected primary or recurrent low- or high-grade glioma received an ¹⁸F-FACBC PET/MRI examination before surgery. PET and MRI were used for diagnostic assessment, and for guiding tumor resection and histopathological tissue sampling. PET uptake, tumor-to-background ratios (TBRs), time-activity curves, as well as PET and MRI tumor volumes were evaluated. The sensitivities of lesion detection and to detect glioma tissue were calculated for PET, MRI, and combined PET/MRI with histopathology (biopsies for final diagnosis and additional image-localized biopsies) as reference.

Overall sensitivity for lesion detection was 54.5% (95% confidence interval [CI], 23.4–83.3) for PET, 45.5% (95% CI, 16.7–76.6) for contrast-enhanced MRI (MRI_CE), and 100% (95% CI, 71.5–100.0) for combined PET/MRI, with a significant difference between MRI_CE and combined PET/MRI (P = 0.031). TBRs increased with tumor grade (P = 0.004) and were stable from 10 minutes post injection. PET tumor volumes enclosed most of the MRI_CE volumes (>98%) and were generally larger (1.5–2.8 times) than the MRI_CE volumes. Based on image-localized biopsies, combined PET/MRI demonstrated higher concurrence with malignant findings at histopathology (89.5%) than MRI_CE (26.3%).

Low- versus high-grade glioma differentiation may be possible with ¹⁸F-FACBC using TBR. ¹⁸F-FACBC PET/MRI outperformed MRI_CE in lesion detection and in detection of glioma tissue. More research is required to evaluate ¹⁸F-FACBC properties, especially in grade II and III tumors, and for different subtypes of gliomas.

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.

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.

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.