GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP “Fluorodopa F 18 Injection”

Abstract

Our efforts in producing FDOPA following all aspects of GMP requirements have resulted in a product with the USP quality and certified as GMP complied. The routine production yields enough doses for three to four whole-body scans in each batch. The issues discussed in the report provide good reference for producers planning in routine production for PET drugs that are not commonly produced or with complicated compendial quality control tests.

Automated striatal uptake analysis of 18F-FDOPA PET images applied to Parkinson’s disease patients

“…All antiparkinsonian medications were stopped at least 12 h before the PET studies and subjects were given 100 mg of carbidopa 1 h before FDOPA administration. FDOPA was produced in our GMP facility as described elsewhere [17]. Static three-dimensional acquisition was performed 2 h after the intravenous injection of 185 MBq FDOPA with a GE Discovery ST PET/CT scanner (GE Healthcare, Chalfont St Giles, Buckinghamshire, UK) for 30 min.…”

Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[76Br]bromo-3-(E)-butenoic Acid (BrVAIB) for Brain Tumor Imaging

“…We did not attempt to optimize the specific activity of [ 76 Br] 5 because amino acid transporters typically have K m values in μM to low mM ranges, and endogenous amino acids are present in relatively high concentrations. Thus, high specific activity is typically not necessary for imaging with radiolabeled amino acids as has been shown with [ 18 F]FDOPA prepared in relatively low specific activity through carrier-added electrophilic [ 18 F]fluorination . Modifications to the production of 76 Br, reduction of potential sources of nonradioactive bromide in the solutions and materials used in the radiosynthesis starting from larger amounts of 76 Br of the final product, and HPLC purification to remove nonradioactive compounds arising from the precursor are possible methods to increase the specific activity.…”

Imaging of Brain Tumours

“…[91,92] A fully automated method for synthesis of FDOPA is now also available. [93,94] However, there are limitations with this approach, such as the requirement of additional equipment, precautions for dealing with 18 F in gaseous form, and the low radiotracer production rate. [95,96] Recent developments have seen the introduction of nucleophilic approaches.…”