Additional file 1 of GMP production of 6-[18F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience
Creators: name: Andersen, Valdemar L.
name: Soerensen, Mikkel A.
name: Dam, Johan Hygum
name: Langkjaer, Niels
name: Petersen, Henrik
name: Bender, Dirk Andreas
name: Fugloe, Dan
name: Huynh, Tri Hien Viet
Publisher: name: figshare
Year: 2021
Subjects: subject: Biochemistry
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences

description: Additional file 1: Supplemental Table 1. AUH PET center has three cyclotrons for PET isotope production as its disposal, and thus, three different paths for the production of [18F]F2 are available. The cyclotron production parameters for the three different cyclotrons are summarized below. All three procedures involve proton beam irradiation of [18O]O2 gas, followed by cryogenic recovery of the [18O]O2 gas, and finally a consecutive proton irradiation on a noble gas containing 19F2 for F-18 recovery. All targets are evacuated for 30 min prior to usage in order to ensure proper operation. For the IBA setup, consecutive filling and emptying with Ne gas is necessary prior to evacuation. Supplemental Fig. 1. Setup for production of [18F]1 on the custom-build synthesis platform at AUH. The platform consists of a series of 12 V three-way valves, an electrical heater, a vacuum membrane pump, a pneumatically actuated HPLC injector with 5 ml stainless steel loop, HPLC pump, and a photodiode radio detector. The flow of [18F]F2 is adjusted by a needle valve. Where needed, overpressure is generated by helium. The fluorination reactor and the hydrolysis vessel are conventional Pyrex glassware. For the other containers, conventional single use sterile medical plastic materials are used. Supplemental Fig. 2. GUI of the LabVIEW application used for controlling the synthesis platform at AUH. Supplemental Fig. 3. Flowchart for the production of [18F]1 at AUH. Supplemental Fig. 4. Tracerlab MX layout within the synthesis unit control software at OUH. Supplemental Fig. 5. Flowchart for the synthesis of [18F]1 at OUH. Supplemental Fig. 6. Setup of the Tracerlab MX at OUH just before start of synthesis with vial contents and SPE cartridge types given. Supplemental Fig. 7. Trasis AllinOne layout within the synthesis unit control software at HUH. Supplemental Fig. 8. Setup of the Trasis AiO at HUH just before the start of synthesis with all the reagent vials/containers labelled. Note that the alkylation vial (vial D) is hidden behind the WFI IV bag. The contents of the different vials/syringes are as follows: Vial A contains QMA eluent (K222 and K2CO3 in methanol), vial B contains precursor 7 in DMF, syringe C contains 45% potassium hydroxide, vial D contains the Schiff base N-(diphenylmethylene)glycine tert-butyl ester and the phase-transfer catalyst as solids, vial E contains dichloromethane, vial F contains solid NaBH4, vial G contains ethanol, and vial H contains hydroiodic acid. An IV bag containing water for injections (WFI) is installed in position I, vial J contains solid ascorbic acid, and vial K contains a mixture of citric acid and trisodium citrate dihydrate in WFI (i.e. sterile citrate buffer). Supplemental Table 2. The specifications for preparations of [18F]1 at AUH. Supplemental Table 3. The specifications for preparations of [18F]1 at OUH. Supplemental Table 4. The specifications for preparations of [18F]1 at HUH. Supplemental Fig. 9. UV- and radiodetected HPLC chromatograms of a batch of [18F]1 at AUH. Supplemental Fig. 10. UV- and radiodetected HPLC chromatograms for the determination of the enantiomeric purity of a batch of [18F]1 at AUH. Supplemental Fig. 11. UV- (283 nm) and radioanalytical HPLC trace for a batch of [18F]1 produced at OUH. The UV-trace is given in blue, while the radiodetected chromatogram is given in red. Supplemental Fig. 12. UV- (280 nm) and radioanalytical HPLC trace for a batch of [18F]1 produced at HUH. The UV-trace is given in green, while the radiodetected chromatogram is given in purple. Supplemental Fig. 13. Radiodetected HPLC chromatogram for the determination of the enantiomeric purity of a batch of [18F]1 at HUH. The batch is the same as the one used in Supplemental Fig. 12. Supplemental Fig. 14. The alkylation vial (vial D) before (left) and after (right) addition of DCM. Note the powdered solids sticking to the sides and bottom of the vial before addition of solvent. After addition of DCM, several specks of suspended solids can be seen sticking to the bottom of the vial.