First-in-Man Noninvasive Initial Diagnostic Approach of Primary CNS Lymphoma Versus Glioblastoma Using PET With 18F-Fludarabine and l-[methyl-11C]Methionine

Abstract

Objectives: This study sought to assess 18 F-fludarabine ( 18 F-FLUDA) PET/ CT's ability in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastoma multiformes (GBMs). Patients and Methods: Patients harboring either PCNSL (n = 8) before any treatment, PCNSL treated using corticosteroids (PCNSLh; n = 10), or GBM (n = 13) were investigated with conventional MRI and PET/CT, using 11 C-MET and 18 F-FLUDA. The main parameters measured with each tracer were SUV T and T/N ratios for the first 30 minutes of 11 C-MET acquisition, as well as at 3 different times after 18 F-FLUDA injection. The early 18 F-FLUDA uptake within the first minute of injection was equally considered, whereas this parameter was combined with the later uptakes to obtain R FLUDA 2 and R FLUDA 3 ratios. Results: No significant differences in 11 C-MET uptakes were observed among PCNSL, PCNSLh, and GBM. With 18 F-FLUDA, a clear difference in dynamic GBM uptake was observed, which decreased over time after an early maximum, as compared with that of PCNSL, which steadily increased over time, PCNSLh exhibiting intermediate values. The most discriminative parameters consisting of R FLUDA 2 and R FLUDA 3 integrated the early tracer uptake (first 60 seconds), thereby provided 100% specificity and sensitivity. Conclusions: 18 F-FLUDA was shown to likely be a promising radiopharmaceutical for differentiating PCNSL from other malignancies, although a pretreatment with corticosteroids might compromise this differential diagnostic ability. The diagnostic role of 18 F-FLUDA should be further investigating, along with its potential of defining therapeutic strategies in patients with PCNSL, while assessing the treatments' effectiveness.

Role of Positron Emission Tomography in Primary Central Nervous System Lymphoma

“…18 F-FDB showed high uptake in CNS lymphomas, while the tracer was rapidly cleared from glioma cells. These results have recently been confirmed in a first-in man study using PET with 18 F-FDB [ 92 ]. Early results on 18 F-FDB also showed that the tracer uptake could be independent of BBB leakage, which should allow metabolic characterization of atypical PCNSL [ 91 , 93 ].…”

Amino acids in hematologic malignancies: Current status and future perspective

“…Furthermore, in primary CNS lymphoma patients, higher tumor-to-normal ratio of 11 C-MET PET/CT was significantly related to worse PFS, while that of 18 F-FDG PET/CT showed no significant relationship to prognosis ( 106 ). However, other studies claimed that 11 C-MET PET/CT failed to differentiate primary CNS lymphoma or GBMs ( 107 ). In abdomen detection, 11 C-MET PET/CT could not effectively differentiate the physiologic high Met uptake or malignant high uptake in pancreas and liver, limiting its application to abdomen detection ( 106 ).…”

PET Agents for Primary Brain Tumor Imaging

“…More than A1AR this receptor plays a crucial role in inflammatory processes involving microglia. 18 F-FLUDA also specifically links with Blymphocytes and a recent first-in-human study demonstrated the potential to distinguish primary central nervous system lymphomas from glioblastoma (143). Nevertheless, whether these agents readily cross the BBB is as yet unknown, precluding clear statements on uptake interpretation.…”