Multi-organ kinetic modeling for Na[¹⁸F]F pre-clinical total-body PET studies

Background: Total-body positron emission tomography (PET), already well-established in the pre-clinical setting, makes it possible to study multi-parameters in biological systems as a whole, rather than focusing on single tissues analysis. Simultaneous kinetic analysis of multiple organs poses some daunting new challenges. Purpose: To explore quantifying the pharmacokinetics of Na[¹⁸F]F in multiple dissimilar murine organs simultaneously in vivo with total-body PET imaging using different compartmental models for each organ and a shared cardiovascular system. Methods: Six mice underwent a 60-min total-body PET scan following intravenous bolus injection of Na[¹⁸F]F. Compartmental models were constructed for each organ (heart, lungs, liver, kidneys, and bone) using an image derived input function. Non-linear least squares fitting of a model that connects the five organs to a shared cardiovascular system was used to analyze both the first 3 min of data and the full hour. Analysis was repeated 5000 times using different initial parameter values for each duration, permitting analysis of correlations between parameters. Results: The models give a good qualitative account of the activity curves irrespective of the duration of the data; however, the quality of the fits to 3 min of data (average (Formula presented.) is 2.72) was generally better. Comparison of perfusion values to literature values was possible for the liver and lungs with the former (liver, 0.540 ± 0.177 mL/ml/min) being well-above expectations and the latter (lungs, 0.184 ± 0.413 mL/ml/min) in rough agreement. Correlations between microparameter values (especially affecting k₂) caused very noticeable problems for data modeling from both the kidneys and the femur. Conclusion: The present study demonstrates an approach to performing kinetic modeling for multiple organs simultaneously with Na[¹⁸F]F. The observed correlations between microparameter values remain a challenge. Nonetheless, many microparameters can be estimated reliably with a quantitative analysis of perfusion being possible for some organs.