Optimized Methodology for Reference Region and Image-Derived Input Function Kinetic Modeling in Preclinical PET

Positron emission tomography (PET) imaging of small animals is often used for assessing biodistribution of a novel radioligand and pharmacology in small animal models of disease. PET acquisition and processing settings may affect reference region or image-derived input function (IDIF) kinetic modeling estimates. We examined four different factors in comparing quantitative results: 1) effect of reconstruction algorithm; 2) number of maximum a posteriori (MAP) iterations; 3) strength of the MAP prior; and 4) attenuation and scatter. The effect of these parameters has not been explored for small-animal reference region and IDIF kinetic modeling approaches. Dynamic PET/CT scans were performed in three species with three different tracers: 1) house sparrows with [¹¹C]raclopride; 2) rats with [¹⁸F]AS2471907 ( $11\boldsymbol{\beta }$ HSD1); and 3) mice with [¹¹C]UCB-J (SV2A). FBP yielded lower kinetic modeling estimates compared to 3D-OSEM-MAP reconstructions, in sparrow and rat studies. Target resolutions (MAP prior strength) of 1.5 and 3.0 mm demonstrated reduced $V_{T}$ in rats but only 3.0 mm reduced $BP_{ND}$ in sparrows. Therefore, the use of the highest target resolution (0.8 mm) is warranted. We demonstrated using kinetic modeling that forgoing CT-based attenuation and scatter correction may be appropriate to improve animal throughput when using short-lived radioisotopes in sparrows and mice. This work provides recommendations and a framework for future optimization of kinetic modeling for preclinical PET methodology with novel radioligands.