Nucl Med Mol Imaging.  2022 Jun;56(3):127-136. 10.1007/s13139-022-00742-w.

Experience of 6-L-[ ¹⁸ F]FDOPA Production Using Commercial Disposable Cassettes and an Automated Module

• Nanabala R
• Ambikalmajan Pillai MR
• Gopal B

• KMID: 2530645
• DOI: http://doi.org/10.1007/s13139-022-00742-w

Abstract

Purpose
The clinical demand of 6-L-[ ¹⁸ F] FDOPA is gaining rapidly for imaging neurodegenerative diseases by using positron emission tomography. Hence, large-scale production of 6-L-[ ¹⁸ F] FDOPA is necessary. This paper describes our experience on the production of 6-L-[ ¹⁸ F]FDOPA via nucleophilic synthesis using NEPTIS module and a commercially available cassette based chemistry. Method 6-L-[ ¹⁸ F]FDOPA production could be completed in three synthetic steps by using ABX nitro precursor. The precursor is first labeled with ¹⁸ F by replacing a –NO 2 leaving group followed by purification using a solid phase cartridge. In the subsequent step, the radiolabeled precursor is oxidized using meta chloroperoxy benzoic acid hydrolyzed to remove the four different protecting groups. The product is finally purified in a series of solid phase cartridges to yield radiochemically pure 6-L-[ ¹⁸ F]FDOPA.
Results
Total 36 batches of 6-L-[ ¹⁸ F]FDOPA were produced. The decay uncorrected yield were 5.5 ± 1.5% (n = 33) which corresponds to a decay corrected yield of 11.8 ± 3.2% (n = 33). The radiochemical purity of the product obtained is always > 95%.
Conclusion
The yields obtained are low and hence there is a need to improve synthetic chemistry. In order to understand the efficiency of each step, a detailed analysis using the radioactive traces obtained from the automated module was carried out. The radiolabeling yield of precursor is only about 50% and there is subsequent reduction in activity in the oxidation as well as hydrolysis steps. Despite the low radiochemical yields, the product obtained was suitable for imaging.

Keyword

FDOPA; [ ¹⁸ F]FDOPA; Nucleophilic FDOPA production; mCPBA; Parkinson’s disease