RT Journal Article SR Electronic T1 Radiosynthesis of [18F]-flumazenil and its clinical utilization. JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 470 OP 470 VO 61 IS supplement 1 A1 Pardeep Kumar A1 Chandana Nagaraj A1 Raman Joshi A1 N. SRIDHAR GOUD A1 Dinesh Kumar A1 Vittal Korann A1 Sandhya Mangalore A1 Naren Rao YR 2020 UL http://jnm.snmjournals.org/content/61/supplement_1/470.abstract AB 470Introduction: [18F]-flumazenil (FMZ) has been synthesized by various strategies involving complex purification by on-line high-performance liquid chromatography (HPLC) and also by solid-phase cartridges. [18F]-FMZ has been used for the assessment of the gamma-aminobutyric acid (GABA) receptors by positron emission tomography (PET). We have tried various solid-phase extraction (SPE) cartridges combinations and calculated yields. The preparation was used for the evaluation of benzodiazepine receptors in controls and Schizophrenia patients. Objective: To synthesize [18F]-flumazenil using various combinations of the solid phase cartridges to get a higher yield and utilize it for imaging benzodiazepine receptors in control and clinical subjects. Method: [18F] was produced by standard nuclear reaction using [H2O18] as a target material. The precursor nitromazenil was procured from Sycom, Netherlands and ABX, Germany. The radio-fluorination was standardized for various parameters like temperature (130-160°C), precursor concentration (3-5 mg), various combination of SPE cartridges (HLB, tC18, C18, and alumina). the crude mixture was diluted with acidic water and passed through various combinations of the SPE cartridges (HLB + tC18, HLB + C18, C18 + Alumina) and the final product eluted by using 2.0 mL of 20% ethanol/ phosphate buffer (pH-4.0). The mechanism of labeling is nucleophilic substitution and carried out in the FX2N tracer lab module. The radiochemical purity, in-vitro stability, and specific activity was calculated by HPLC equipped with UV/Vis and radioactivity detector. pH, residual solvent, sterility testing, endotoxin levels were evaluated for patient preparations. Briefly 170 ± 20 MBq of [18F]-FMZ was injected intravenously into the control and patient group (n = 5, each group). The dynamic scans were acquired on Siemens Biograph mMR (PET-MR) for 90 min. The images were processed using pMOD software. Results: The labeling was found to be maximum by using K18F/kryptofix complex in the DMF at 160°C for 30 min. An equimolar concentration of [K/K2.2.2]+18F-/precursor was used and the incorporation of 18F in the flumazenil was found to be 19 ± 3%. The combination of C18 and alumina cartridges gave the highest yield (15 ± 2 %) as compared to 1-2% by the other two combinations. The radiochemical purity was 95 ± 3 % as evaluated by Radio-HPLC with retention time at 15.4 ± 0.3 min (n = 20) with a specific activity of 6000 ± 1500 Χι/μμολ. This method was adopted for automation and a sequence (for FX2N) was created by us to run the protocol for clinical production of the [18F]-flumazenil. The images showed binding to central benzodiazepine (BZ) receptor in BZ receptor rich regions, such as the neocortex, the regional time-activity curve showed the highest uptake at 12 min in neocortical regions, followed by cerebellum, thalamus and putamen, and low uptake in the brain stem regions (pons and medulla). Binding potential values obtained by the reference tissue models were in good agreement with those obtained by the kinetic analysis. Conclusions: [18F]-flumazenil was synthesized with higher radiochemical purity and a better agent for imaging benzodiazepine receptors.