Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A).
PURPOSE
Synaptic abnormalities have been implicated in a variety of neuropsychiatric disorders, including epilepsy, Alzheimer's disease, and schizophrenia. Hence, PET imaging of the synaptic vesicle glycoprotein 2A (SV2A) may be a valuable in vivo biomarker for neurologic and psychiatric diseases. We previously developed [11C]UCB-J, a PET radiotracer with high affinity and selectivity toward SV2A; however, the short radioactive half-life (20 min for 11C) places some limitations on its broader application. Herein, we report the first synthesis of the longer-lived 18F-labeled counterpart (half-life: 110 min), [18F]UCB-J, and its evaluation in nonhuman primates.


METHODS
[18F]UCB-J was synthesized from the iodonium precursors. PET imaging experiments with [18F]UCB-J were conducted in rhesus monkeys to assess the pharmacokinetic and in vivo binding properties. Arterial samples were taken for analysis of radioactive metabolites and generation of input functions. Regional time-activity curves were analyzed using the one-tissue compartment model to derive regional distribution volumes and binding potentials for comparison with [11C]UCB-J.


RESULTS
[18F]UCB-J was prepared in high radiochemical and enantiomeric purity, but low radiochemical yield. Evaluation in nonhuman primates indicated that the radiotracer displayed pharmacokinetic and imaging characteristics similar to those of [11C]UCB-J, with moderate metabolism rate, high brain uptake, fast and reversible binding kinetics, and high specific binding signals.


CONCLUSION
We have accomplished the first synthesis of the novel SV2A radiotracer [18F]UCB-J. [18F]UCB-J is demonstrated to be an excellent imaging agent and may prove to be useful for imaging and quantification of SV2A expression, and synaptic density, in humans.
['Li|Songye|S|http://orcid.org/0000-0002-6096-8756', 'Cai|Zhengxin|Z|', 'Zhang|Wenjie|W|', 'Holden|Daniel|D|', 'Lin|Shu-Fei|SF|', 'Finnema|Sjoerd J|SJ|', 'Shirali|Anupama|A|', 'Ropchan|Jim|J|', 'Carre|Stephane|S|', 'Mercier|Joel|J|', 'Carson|Richard E|RE|', 'Nabulsi|Nabeel|N|', 'Huang|Yiyun|Y|']
D000818:Animals D060326:Chemistry Techniques, Synthetic D005260:Female D005462:Fluorine Radioisotopes D008253:Macaca mulatta D008297:Male D008562:Membrane Glycoproteins D049268:Positron-Emission Tomography D011725:Pyridines D011760:Pyrrolidinones D011854:Radiochemistry
PET SV2A Radiotracer Nonhuman primates Alzheimer’s disease Fluorination