Longitudinal Comparative Quantification of [18F]RO948 and florzolotau (18F) PET in the TgF344-AD Rat Model.

Purpose Tau PET (positron emission tomography) quantification in advanced AD (Alzheimer’s disease) animal models remains insufficiently harmonized, particularly for recently developed tau tracers. Here, we compared the longitudinal performance and quantification of [ ¹⁸ F]RO948 and florzolotau (18F) PET in the TgF344-AD rat model to identify tracer-specific methodological constraints and robust outcome measures. Methods TgF344-AD and wild-type rats (n = 6–10) underwent dynamic PET-CT with [ ¹⁸ F]RO948 at 10, 14, 18, and 22 months and with florzolotau (18F) at 18 and 22 months. Quantification included regional SUV, SUVR, two-step reference tissue modelling (SRTM2), plasma radiometabolite analysis, and in vitro autoradiography. For florzolotau (18F), brainstem-based modelling was used to derive BP _ND and evaluate SUVR time windows. Results [ ¹⁸ F]RO948 showed progressively increasing late signal in cortex and cerebellum, together with skull uptake and plasma radiometabolites. Late-frame quantification was unreliable, and SUV _20–35 was selected as a pragmatic metric. However, [ ¹⁸ F]RO948 signal increased with age in both Tg and wild-type rats, showed limited genotype separation, lacked a valid reference region, and displayed a non-tau binding component in vitro . In contrast, florzolotau (18F) showed stable washout kinetics, no evidence of radio-defluorination, and marked group differences in tau-relevant regions. The brainstem supported SRTM2 modelling, while SUVR _65–90 strongly correlated with BP _ND , supporting its use as a practical semi-quantitative metric. Conclusion In our study, tau PET quantification in TgF344-AD rats was strongly tracer-dependent. While florzolotau (18F) provides a robust framework for longitudinal tau assessment in this model, the limitations of [ ¹⁸ F]RO948 substantially restrict the interpretability and use of this tracer.