The synthesis of [18F]PSMA-1007 and [18F]FDG solutions for injection was conducted on-site at the Radiopharmaceutical Chemistry Laboratory of Turku PET Centre. [18F]FDG was synthesized following an analogous procedure as described previously [15 (link)]. A FASTLab® synthesizer (GE Healthcare, Waukesha, WI, USA) and FDG-phosphate cassettes were used for the production. The radiochemical purity exceeded 98%. [18F]PSMA-1007 was synthesized with TRASIS AllInOne synthesizer (TRASIS Radiopharma, Ans, Belgium) using the single-use cassettes supplied by TRASIS and reagents supplied by ABX (ABX advanced biochemical compounds Gmb, Radeberg, Germany). The radiochemical purity exceeded 93%.
Fastlab synthesizer
Manufactured by GE Healthcare
Sourced in United States
The FASTlab synthesizer is a compact, automated system designed for the synthesis of radiopharmaceuticals. It provides a controlled environment for the production of medical isotopes used in nuclear medicine imaging procedures.
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10 protocols using fastlab synthesizer
1
Synthesis of [18F]PSMA-1007 and [18F]FDG for Injection
2
Synthesis of [18F]Flutemetamol for PET Imaging
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[18F]Flutemetamol was synthesized according to methods described in the patent WO 2007/020400 A1 “Fluorination process of anilide derivatives and benzothiazole fluorinate derivatives as in vivo imaging agents”. FASTlab™ synthesizer (GE Healthcare, Waukesha, WI, USA) and single-use disposable cassettes designed for [18F]Flutemetamol production were used. The molar activity was 936 ± 390 GBq/μmol (mean ± SD, n = 11) at the end of synthesis, and the non-decay-corrected radiochemical yield was 20% ± 5%. Radiochemical purity was 95% ±1%.
3
Radiosynthesis of [18F]FDG and [18F]F-DPA
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[18F]FDG was synthesized at the Radiopharmaceutical Chemistry Laboratory of Turku PET Centre using the FASTlab synthesizer (GE Healthcare) as described previously [25 ]. Radiochemical purity exceeded 98% in all syntheses, and the molar activity (Am) at the end of the synthesis (EOS) was > 100 GBq/μmol.
[18F]F-DPA was synthesized via two different approaches resulting in different Ams. High Am (360–900 GBq/μmol at EOS) [18F]F-DPA was produced by a copper-mediated nucleophilic 18F-fluorination methodology [26 ]. The electrophilic syntheses of [18F]F-DPA, resulting in lower Am (10 GBq/μmol at EOS), were performed according to previously described procedures [24 ].
[18F]F-DPA was synthesized via two different approaches resulting in different Ams. High Am (360–900 GBq/μmol at EOS) [18F]F-DPA was produced by a copper-mediated nucleophilic 18F-fluorination methodology [26 ]. The electrophilic syntheses of [18F]F-DPA, resulting in lower Am (10 GBq/μmol at EOS), were performed according to previously described procedures [24 ].
4
Automated Radiosynthesis of [18F]GE-180
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[18F]GE-180 was prepared by direct nucleophilic [18F] fluorination of its corresponding mesylate precursor. The preparation was performed on a GE FASTlab™ synthesizer with cartridge SPE purification and formulation [36 (link)]. Radiochemical purity was 96 ± 1 % (seven production runs) and the specific activity was 175 ± 38 GBq/μmol (seven production runs) at the end of synthesis (see Supplementary Fig. 2 ).
5
Synthesis of 18F-Fluciclatide Radiotracer
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The radiotracer was manufactured at the Clinical Research Imaging Centre, University of Edinburgh on an automated module (FASTlab synthesizer; GE Healthcare) by coupling an amino-oxy-functionalised peptide precursor (AH111695) with 4-18F-fluorobenzaldehyde at pH 3.5 to form 18F-fluciclatide. Full description of this synthesis has been published.5–7 (link)
6
Radiosynthesis of [18F]FDG and [18F]FTP
7
Radiolabeling Procedure for [18F]FDG
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[18F]FDG (37 batches) was synthesized at the Radiopharmaceutical Chemistry Laboratory of Turku PET Centre using the FASTlab synthesizer (GE Healthcare, Waukesha, WI, USA) as described previously6 (link). Radiochemical purity exceeded 95% in all syntheses.
8
Fluorinated Imaging Agent Synthesis
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[18 F]flutemetamol was produced with a FASTLab® Synthesizer (GE Healthcare), following analogous procedures to those described in the patent, WO 2007/020400 A1 ‘Fluorination process of anilide derivatives and benzothiazole fluorinate derivatives as in vivo imaging agents’. The specific radioactivity of [18 F]flutemetamol was >1 TBq/μmol at synthesis completion (N = 34). Radiochemical purity exceeded 92%.
9
Synthesis and PET Imaging of [18F]GE-180 Tracer
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[ 18 F]GE-180, a translocator protein ligand [110] , was synthesized on a FASTlab synthesizer (GE Healthcare) with precursor and reagent kits in single-use cassettes (GE Healthcare) according to the manufacturer's instructions. The radiochemical purity of the final formulated radiotracer was > 95% as determined by HPLC. The molar activity was determined at the time of injection as 576 ± 283 GBq/μmol. Three small-animal PET scanners (Inveon, Siemens, Erlangen, Germany) and dedicated rat brain beds (Jomatik Gmbh, Tuebingen, Germany) with stereotactic holders and temperature feedback control units (Medres, Cologne, Germany) were used. These ensured the delivery and removal of the anesthesia gas and stabilized the body temperature at 37 °C during the PET data acquisition. Anesthesia was induced by placing the animals in knock-out boxes and delivering 2% isoflurane in oxygen air. Subsequently, a 24 G catheter (BD Insyte, NJ, USA) was placed into the tail vein for the tracer and/or i.v. anesthesia administration. Afterward, animals of cohort 1 were anesthetized with 2% isoflurane vaporized in 1.0 L/min of oxygen. Animals of cohort 2 received a medetomidine bolus injection (0.05 mg/kg) and the anesthesia was switched to constant medetomidine infusion (0.1 mg/kg/h), and 0.5% isoflurane in air during the scan time, as adapted from the literature [111] .
10
Radiochemical Production and Characterization
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All reagents were commercial products and used without further purification unless otherwise indicated. Animal studies were approved by the local institutional animal care and use committee and performed according to the Guide for the Care and Use of Laboratory Animals published by the U.S. National Institutes of Health (NIH publication 85-23, revised 1996 (20) ).
Radiochemistry 14 C-methionine was purchased from PerkinElmer. 11 C-methionine and 18 F-FDG were produced in-house with a 16-MeV Cyclotron (PETtrace 6; GE Healthcare), as described previously (21) . Briefly, 18 F-FDG was produced on a FASTlab synthesizer (GE Healthcare), and 11 C-methionine was synthesized on a TRACERlab FX-C Pro module (GE Healthcare) by an online 11 C-methylation of L-homocysteine. 18 F-fluorobenzyl triphenyl phosphonium, a myocardial perfusion PET tracer, was prepared as reported previously (22, 23) . All radiolabeled ligands were analyzed by high-performance liquid chromatography or thin-layer chromatography at the end of syntheses to confirm radiochemical identity and purity (.95%).
Radiochemistry 14 C-methionine was purchased from PerkinElmer. 11 C-methionine and 18 F-FDG were produced in-house with a 16-MeV Cyclotron (PETtrace 6; GE Healthcare), as described previously (21) . Briefly, 18 F-FDG was produced on a FASTlab synthesizer (GE Healthcare), and 11 C-methionine was synthesized on a TRACERlab FX-C Pro module (GE Healthcare) by an online 11 C-methylation of L-homocysteine. 18 F-fluorobenzyl triphenyl phosphonium, a myocardial perfusion PET tracer, was prepared as reported previously (22, 23) . All radiolabeled ligands were analyzed by high-performance liquid chromatography or thin-layer chromatography at the end of syntheses to confirm radiochemical identity and purity (.95%).
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