PT  - JOURNAL ARTICLE
AU  - John Gerdes
AU  - Syed Ahmed
AU  - Michael Braden
AU  - Shorouk Dannoon
AU  - Joseph Blecha
AU  - Henry VanBrocklin
TI  - Radiosynthesis, Rodent and Non-human Primate Studies of a Novel PET Tracer for the Excitatory Amino Acid Transporter 2 (EAAT2) in the CNS
DP  - 2015 May 01
TA  - Journal of Nuclear Medicine
PG  - 1100--1100
VI  - 56
IP  - supplement 3
4099  - http://jnm.snmjournals.org/content/56/supplement_3/1100.short
4100  - http://jnm.snmjournals.org/content/56/supplement_3/1100.full
SO  - J Nucl Med2015 May 01; 56
AB  - 1100 Objectives Our objective has been to develop a novel PET imaging tracer of the L-glutamate (L-Glu) transporter EAAT2 (Excitatory Amino Acid Transporter 2) found on astrocytes in the CNS. Transport by EAAT2 is the primary regulatory mechanism for clearance of extracellular levels of L-Glu. Excitotoxic CNS injury promoted by elevated L-Glu can be a result from altered regional astrocyte EAAT2 activity and/or cell surface expression. Our hypothesis is that an EAAT2 PET tracer will mark these in vivo CNS changes. We sought to develop low and high specific activity radiosyntheses of the EAAT2 tracer [18F]1 and evaluate these radioligand forms within rodent and monkey CNS tissues.Methods Respective radiosyntheses of [18F]1 were performed using either an electrophilic [18F]F2 fluoro-destannylation reaction or a nucleophilic [18F]F- fluoro-denitration transformation. CNS {ET imaging studies (i.v. injection, 0-90 min scans) were performed in male rats with an Inveon microPET scanner and also in male and female rhesus monkeys with a P4 scanner.Results [18F]1 was prepared in > 95% radiochemical purity by both methods in 2-4 hours (EOS). A mean specific activity of ~2.3 Ci/mmol (n=20) was obtained by the electrophilic method and ~ 1,300 Ci/mmol (n=8) by the nucleophilic radiosynthesis. Within both rats and monkeys [18F]1 results in high uptake of radioactivity in thalamus, motor cortex, frontal cortex and other ROIs, including spine, consistent with high EAAT2 densities, in which tracer signal to noise is enhanced with the high specific activity tracer form.Conclusions [18F]1 is a first-in-class CNS [18F]-tracer for the astrocytic EAAT2 target in rodents and non-human primates. This tracer is considered suitable for advancement for human studies.Research Support The Robert Packard Center for ALS Research, Johns Hopkins University; P2ALS; ALS Association and NIH P30-NS055022.