Quantification of inflammation in the rat brain using [¹¹C]PBR28 PET

Objectives The non-invasive, longitudinal measurement of neuroinflammation in rodent models may aid our understanding of the pathogenesis of diseases such as Alzheimer’s and Parkinson’s. PBR28 binds to translocator protein (18 kDa), which is highly expressed by activated microglia. We tested various methods to quantify [¹¹C]PBR28 binding in the rat brain using PET. The analysis is challenging due to the absence of a non-binding region, the limited structural information present in the [¹¹C]PBR28 distribution, and the potential for variable tracer metabolism.

Methods [¹¹C]PBR28 PET imaging and in vitro autoradiography was performed in a unilaterally 6-hydroxydopamine (6OHDA) lesioned rat, normal control rats and rats treated systemically with lipopolysaccharide (LPS).

Results In the lesioned rat, increased [¹¹C]PBR28 binding was observed by PET in the striatal region where 6OHDA was injected and in the cortex immediately superior. The [¹¹C]PBR28 distribution was similar between PET and autoradiography. Tracer uptake at the site of lesioning was 1.6 times that in the contralateral region for [¹¹C]PBR28 PET, compared to a binding ratio of 2.0 for autoradiography. The injected region had reduced [¹¹C]DTBZ (dihydrotetrabenazine) binding, confirming loss of dopaminergic terminals. [¹¹C]PBR28 binding in neuronal tissue was low compared to that for ventricular walls. Injection of LPS caused observable sickness. Initial results from autoradiography in such rats showed increased [¹¹C]PBR28 binding in several brain regions, unlike our initial findings from PET data for a similar cohort (n=4; ratio of whole-brain SUV between LPS and vehicle treated rats =1.01). Further testing and quantitative analyses are underway.

Conclusions From these initial data we conclude that [¹¹C]PBR28 is a useful ligand for measurement of neuroinflammation in the rat using autoradiography, but that further methodological testing is warranted before its routine use as a PET tracer in rats.

Research Support Canadian Institutes of Health Research, The Michael J Fox Foundation for Parkinson's Research