PET Imaging of a Transgenic Tau Rat Model SHR24 with [F]AV1451.

Purpose: Positron Emission Tomography (PET) scans with radioligands targeting tau neurofibrillary tangles (NFT) have accelerated our understanding of the role of misfolded tau in neurodegeneration. While intended for human research, applying these radioligands to small animals establishes a vital translational link. Transgenic animal models of dementia, such as the tau rat SHR24, play a crucial role in enhancing our understanding of these disorders. This study aims to evaluate the utility of SHR24 rat model for PET studies.

Procedures: Dynamic PET scans were conducted in male SHR24 rats and their wild-type SHR (SHRwt) littermates using [F]AV1451. Rapid blood sampling and metabolite analysis were performed to acquire input curves. Time activity curves were obtained from various brain regions over 60 min. Blood-based, 2-Tissue Compartment Model (2-TCM) and Logan graphical analysis were used to obtain kinetic modelling parameters. The ability of reference tissue models to predict the binding potential (BP) were assessed. Autoradiography studies were performed to corroborate the scan data.

Results: Total distribution volume (V) was the best predicted parameter which revealed significantly higher uptake of [F]AV1451 in the cortex (5.8 ± 1.1 vs 4.6 ± 0.7, P < 0.05) of SHR24 rats compared to SHRwt rats. Binding potential obtained from 2-TCM was variable, however BP from reference tissue models detected significantly higher binding in cortex (0.28 ± 0.07 vs 0.20 ± 0.04, P < 0.01 by SRTM) and brainstem (0.14 ± 0.04 vs 0.08 ± 0.02, P < 0.01, by SRTM).

Conclusions: With the ability to detect binding of established radioligand [F]AV1451 in these rats, we have demonstrated the utility of this model for assessing aggregated tau neurobiology by PET, with reference tissue models providing potential for longitudinal studies.