A Pharmacokinetic Model Determination of Time Activity Curves in Radiopharmaceutical Therapy

Radiopharmaceutical therapy (RPT) dosimetry can be challenging to perform due to sparse data measurements and variations in how the time activity curve (TAC) is determined. In this work, a single system of equations was theoretically derived to estimate the TAC.

A pharmacokinetic (PK) model was developed to estimate patient specific rate constants for a given set of body compartments. The PK model and an optimizer were numerically implemented to determine the rate constants and, using these physiologic data, to generate TACs and time integrated activities (TIAs) for 3 tissue systems from clinical data gathered in 5 patients. A fourth (aggregate) tissue compartment is added using conservation of activity considerations.

Feasibility of the PK model was demonstrated by successfully generating TACs and TIAs for all patients in a manner comparable to existing methods in the literature. The data are compared to smaller sampling regimes. Differences between the 3- and 4-compartment models show that conservation of activity considerations should be part of TAC estimations.

The results here suggest a new paradigm in RPT in using the rate constants so identified as a diagnostic tool and as a vehicle to achieving individualized tumorcidal dose and/or the maximum tolerable dose to normal tissues.