Deconvolution of Plasma Pharmacokinetics from Dynamic Heart Imaging Data Obtained by Single Positron Emission Computed Tomography/Computed Tomography Imaging

Plasma pharmacokinetic (PK) data are required as an input function for graphical analysis of single positron emission com-puted tomography/computed tomography (SPECT/CT) and posi-tron emission tomography/CT (PET/CT) data to evaluate tissue influx rate of radiotracers. Dynamic heart imaging data are often used as a surrogate of plasma PK. However, accumulation of ra-diolabel in the heart tissue may cause overprediction of plasma PK. Therefore, we developed a compartmental model, which in-volves forcing functions to describe intact and degraded radiola-beled proteins in plasma and their accumulation in heart tissue, to deconvolve plasma PK of 125I-amyloid beta 40 (125I-Ab40) and 125 I-insulin from their dynamic heart imaging data. The three -compartment model was shown to adequately describe the plasma concentration-time profile of intact/degraded proteins and the heart radioactivity time data obtained from SPECT/CT imaging for both tracers. The model was successfully applied to deconvolve the plasma PK of both tracers from their naive datasets of dynamic heart imaging. In agreement with our previous observations made by conventional serial plasma sampling, the deconvolved plasma PK of 125I-Ab40 and 125I-insulin in young mice exhibited lower area under the curve than aged mice. Further, Patlak plot parameters ex-tracted using deconvolved plasma PK as input function success-fully recapitulated age-dependent plasma-to-brain influx kinetics changes. Therefore, the compartment model developed in this study provides a novel approach to deconvolve plasma PK of ra-diotracers from their noninvasive dynamic heart imaging. This method facilitates the application of preclinical SPECT/PET imag-ing data to characterize distribution kinetics of tracers where si-multaneous plasma sampling is not feasible.SIGNIFICANCE STATEMENT Knowledge of plasma pharmacokinetics (PK) of a radiotracer is necessary to accurately estimate its plasma-to-brain influx. How-ever, simultaneous plasma sampling during dynamic imaging pro-cedures is not always feasible. In the current study, we developed approaches to deconvolve plasma PK from dynamic heart imaging data of two model radiotracers, 125I-amyloid beta 40 (125I-Ab40) and 125I-insulin. This novel method is expected to minimize the need for conducting additional plasma PK studies and allow for accurate estimation of the brain influx rate.