Neuroinflammation is a key pathologic hallmark of numerous neurologic diseases, however, its exact role in vivo is yet to be fully understood. PET imaging enables investigation, quantification, and tracking of different neuroinflammation biomarkers in living subjects longitudinally. One such biomarker that has been imaged extensively using PET is translocator protein 18 kDa (TSPO). Although imaging TSPO has yielded valuable clinical data linking neuroinflammation to various neurodegenerative diseases, considerable limitations of TSPO PET have prompted identification of other more cell-specific and functionally relevant biomarkers. This review analyzes the clinical potential of available and emerging PET biomarkers of innate and adaptive immune responses, with mention of exciting future directions for the field.

Three new positron emission tomography (PET) radiotracers of interest to our functional neuroimaging and translational oncology programs have been prepared through new developments in [11C]CO2 fixation chemistry. [11C]QZ (glutaminyl cyclase) was prepared via a tandem trapping of [11C]CO2/intramolecular cyclization; [11C]tideglusib (glycogen synthase kinase-3) was synthesized through a tandem trapping of [11C]CO2 followed by an intermolecular cycloaddition between a [11C]isocyanate and an isothiocyanate to form the 1,2,4-thiadiazolidine-3,5-dione core; [11C]ibrutinib (Bruton’s tyrosine kinase) was synthesized through a HATU peptide coupling of an amino precursor with [11C]acrylic acid (generated from [11C]CO2 fixation with vinylmagnesium bromide). All radiochemical syntheses are fully-automated on commercial radiochemical synthesis modules and provide radiotracers in 1 – 5% radiochemical yield (non-corrected, based upon [11C]CO2). All three radiotracers have advanced to rodent imaging studies and preliminary PET imaging results are also reported.

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The phenol of 1-(3-(1H-imidazol-1-yl)propyl)-3-(4-hydroxy-3-methoxyphenyl)thiourea was selectively carbon-11 labelled to generate [11C]PBD150 in 7.3% yield from [11C]methyl triflate (non-decay corrected; radiochemical purity ≥95%, specific activity = 5.7 Ci/µmol, n=5). Evaluation of [11C]PBD150 by small animal PET imaging (mouse and rat) determined it does not permeate the blood brain barrier, indicating previously described therapeutic effect in transgenic mice was likely not the result of inhibiting central nervous system glutaminyl cyclase.