Quantification of Volume-of-Distribution of Free-state Radiotracer Using Total-Body PET Kinetic Modeling with Time Delay Correction

Dynamic PET with tracer kinetic modeling is commonly used for characterizing metabolized or bound radiotracer. The characteristics of free-state radiotracer in tissue, however, have been less explored. In this work, we explore quantification of the volume-of-distribution of free state
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F-FDG, V
f
, and demonstrate its potential usefulness in the spleen (a key immune organ) as an example. The evaluation included ten cancer patients who underwent a baseline dynamic FDG scan on the uEXPLORER total-body PET/CT and a follow-up scan after two weeks of immunotherapy. An irreversible two-tissue compartmental model with time delay correction was used for modeling the dynamic FDG PET data. Results show that time delay correction can significantly impact the V
f
quantification and its ability to measure subtle changes in response to intervention. With time delay correction, spleen V
f
was significantly increased post immunotherapy as compared to the pre-treatment scan, while this change was not observed with other kinetic parameters, including FDG net influx rate Ki and delivery rate K1. The results indicate that characterization of free-state radiotracer has the potential to detect early changes, provide novel insights into the physiology underlying therapy, and likely stimulate new clinical applications.