The development of an automated and GMP compliant FASTlab™ Synthesis of [(18) F]GE-180; a radiotracer for imaging translocator protein (TSPO).
The level of the translocator protein (TSPO) increases dramatically in microglial cells when the cells are activated in response to neuronal injury and insult. The radiotracer [(18) F]GE-180 binds selectively and with high affinity to TSPO and can therefore be used to measure neuroinflammation in a variety of disease states. An optimized, automated synthesis of [(18) F]GE-180 has been developed for the GE FASTlab™ synthesizer. The entire process takes place on the single-use cassette. The radiolabelling is performed by nucleophilic fluorination of the S- enantiomer mesylate precursor. The crude product is purified post-radiolabelling using two solid-phase extraction cartridges integrated on the cassette. Experimental design and multivariate data analysis were used to assess the robustness, and critical steps were optimized with respect to efficacy and quality. The average radiochemical yield is 48% (RSD 6%, non-decay corrected), and the synthesis time including purification is approximately 43 min. The radiochemical purity is ≥95% for radioactive concentration ≤1100 MBq/mL. The total amount of precursor-related chemical impurities is 1-2 µg/mL. The use of solid-phase extraction purification results in a robust GMP compliant process with a product of high chemical and radiochemical purity and consistent performance across positron emission tomography (PET) centers.
GE Healthcare, Oslo, Norway.
Torild
T
Wickstrøm
Alan
A
Clarke
Ingvil
I
Gausemel
Eric
E
Horn
Karina
K
Jørgensen
Imtiaz
I
Khan
Dimitrios
D
Mantzilas
Thanushan
T
Rajanayagam
Dirk-Jan
DJ
in 't Veld
William
W
Trigg
D001331:Automation; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D060326:Chemistry Techniques, Synthetic; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D049268:Positron-Emission Tomography / Q000379:methods*; D011786:Quality Control; D011849:Radioactive Tracers; D011854:Radiochemistry / Q000379:methods* / Q000592:standards*; D018079:Receptors, GABA / Q000378:metabolism*; D052616:Solid Phase Extraction
D002227:Carbazoles; D005462:Fluorine Radioisotopes; C571664:GE-180; D011849:Radioactive Tracers; D018079:Receptors, GABA
FASTlab; GE-180; PET tracer; TSPO; neuroinflammation; peripheral benzodiazepine receptor