Fluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111

Objectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7R) is an adenosine triphosphate (ATP)-gated ion-channel, and P2X7R is a key player in inflammation. P2X7R is an emerging therapeutic target in central nervous system (CNS) diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), because P2X7R also plays a pivotal role in neuroinflammation. P2X7R represents a potential molecular imaging target for neuroinflammation via biomedical imaging technique positron emission tomography (PET), and several radioligands targeting P2X7R have been developed and evaluated in animals. In our previous work, we have developed and characterized [11C]GSK1482160 as a P2X7R radioligand for neuroinflammation,2 clinical evaluation of [11C]GSK1482160 in healthy controls and patients is currently underway, and the estimation of radiation dosimetry for [11C]GSK1482160 in normal human subjects has been reported.3 Since the half-life (t1/2) of radionuclide carbon-11 is only 20.4 min, it is attractive for us to develop derivatives of [11C]GSK1482160, which can be labeled with the radionuclide fluorine-18 (t1/2, 109.7 min), and a fluorine-18 ligand would be ideal for widespread use.4 To this end, a series of [18F]fluoroalkyl including [18F]fluoromethyl (FM), [18F]fluoroethyl (FE), and [18F]fluoropropyl (FP) derivatives of GSK1482160 have been prepared and examined as new potential P2X7R radioligands. © 2019 The Authors
Volume 62, Supplement 1 of the Journal of Labelled Compounds & Pharmaceuticals is comprised of the Abstracts from ISRS 2019.
Fluorine 18, Proteins, Ligands, Inflammation, Tracer techniques, Rats
Wyatt, N. A., Safavi-Naeini, M., Wotherspoon, A., Arthur, A., Nguyen, A. P., Parmar, A., Hamze, H., Day, C. M., Zahra, D., Matesic, L., Davis, E., Rahardjo, G. L., Yepuri, N. R., Shepherd, R. K., Murphy, R. B., Pham, T. Q., Nguyen, V. H., Callaghan, P. D., Holden, P. J., Grégoire, M.-C., Darwish, T.A. & Fraser, B. H. (2019). Fluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111. Poster presented at the 23rd International Symposium on Radiopharmaceutical Sciences (ISRS 2019), Beijing, China, 26 to 31 May 2019. In Journal of Labelled Compounds and Radiopharmaceuticals 62(S1), S123-S588. doi:10.1002/jlcr.3725