Radiochemical Synthesis of 4-[18F]FluorobenzylAzide and Its Conjugation with EGFR-Specific Aptamers.

Central nervous system tumors related to gliomas are of neuroectodermal origin and cover about 30% of all primary brain tumors. Glioma is not susceptible to any therapy and surgical attack remains one of the main approaches to its treatment. Preoperative tumor imaging methods, such as positron emission tomography (PET), are currently used to distinguish malignant tissue to increase the accuracy of glioma removal. However, PET is lacking a specific visualization of cells possessing certain molecular markers. Here, we report an application of aptamers to enhancing specificity in imaging tumor cells bearing the epidermal growth factor receptor (EGFR). Glioblastoma is characterized by increased EGFR expression, as well as mutations of this receptor associated with active division, migration, and adhesion of tumor cells. Since 2021, EGFR has been included into the WHO classification of gliomas as a molecular genetic marker. To obtain conjugates of aptamers GR20 and GOL1-specific to EGFR, a 4-[18F]fluorobenzylazide radiotracer was used as a synthon. For the production of the synthon, a method of automatic synthesis on an Eckert & Ziegler research module was adapted and modified using spirocyclic iodonium ylide as a precursor. Conjugation of 4-[18F]fluorobenzylazide and alkyne-modified aptamers was carried out using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with/without the TBTA ligand. As a result, it was possible to obtain 18F-labelled conjugates with 97% radiochemical purity for [18F]FB-GR20 and 98% for [18F]FB-GOL1. The obtained conjugates can be used for further studies in PET analysis on model animals with grafted glioblastoma.

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

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.