Characterization of Tissue Kinetics

Kinetic modeling of radiotracer (or radiopharmaceutical) is the core of dynamic PET/SPECT imaging. The aim of modeling is to interpret kinetic data quantitatively in terms of physiological and pharmacological parameters of a mathematical model, which describes the exchanges (e.g. delivery and uptake) of radiotracer by the tissue. Statistical inferences can then be made regarding the distribution and circulation of tracers within different tissues regions, which are quantitatively represented by the physiological/pharmacological parameters in the model. Successful statistical inference relies heavily on the appropriate use of analysis approaches and a priori knowledge of the underlying system as well as the validity of the assumptions being made. What if we know nothing about the underlying system, or little is known about the tracer characteristics and we are unsure if the assumptions (e.g. tissue homogeneity) being made are valid? The use of kinetic modeling could lead to incorrect inferences about the complex physiological or biochemical processes. In this case, data-driven approaches can provide important clues to what is going on inside the underlying system and how the radiotracer behaves inside the tissue, as they interrogate the measured data to characterize the complex processes, with minimal assumptions and independent of any kinetic model.

Evaluation of soft tissue sarcomas (STS) is a challenging clinical problem because these tumors are very heterogeneous, and the treatment of patients with STS is also very complicated. The most essential step in the diagnostic evaluation of STS is tumor biopsy. PET imaging has the ability to differentiate benign from malignant lesions. It can detect intralesional morphologic variation in soft tissue sarcomas, and it is of value in grading tumor, staging, restaging, and prognosis. Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobi-ologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (18F), its uptake in tissue can be localized and detected quantitatively with high precision by PET. [18F]FMISO uptake has been investigated in various human malignancies [117]. PET imaging with [18F]FMISO, FDG, and 15O-water may provide valuable information complementary to tumor biopsy for better understanding of the biological behavior of STS. As cluster analysis does not rely on tracer assumptions nor kinetic model, it maybe useful in analyzing tissue TACs of STS obtained from [18F]FMISO-PET and FDG-PET, and in looking for any correlations, for instance, tumor volume, hypoxic volume, and vascular endothelial growth factor expression, etc, between different datasets [118].

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