Conference Paper PET Quantification in Molecular Brain Imaging Taking into Account the Contribution of the Radiometabolite Entering the Brain

Ichise, Masanori  ,  Kimura, Yasuyuki  ,  Shimada, Hitoshi  ,  Higuchi, Makoto  ,  Suhara, Tetsuya

A good understanding of the in vivo pharmacokinetics of radioligands is important for accurate PET quantification in molecular brain imaging. For many reversibly binding radioligands for which there exists a brain region devoid of molecular target binding sites called “reference tissue,” data analysis methods that do not require blood data including the standardized uptake value ratio of target-toreference tissue at a “fixed time point” (SUVR) and reference tissue model to estimate binding potential (BPND) are commonly used, the latter being directly proportional to the binding site density (Bavail). Theoretically, BPND is the tissue ratio minus 1 at equilibrium. It is generally believed that radioligands should not ideally produce radiometabolites that can enter the brain because they might complicate accurate quantification of specific binding of the parent radioligand. However, the tissue ratio that contains the contribution of radiometabolite can also be theoretically a valid parameter that reflects the target binding site density. This article describes the validation of the tissue ratio concept using, as an example of our recent PET data analysis approach for a novel radioligand, 11C-PBB3, to quantify pathological tau accumulations in the brain of Alzheimer’s disease patients in which the SUVR and reference tissue model methods using the cerebellar cortex as the reference tissue were validated by the dual-input graphical analysis model that uses the plasma parent and radiometabolite activity as input functions in order to take into account the contribution of the radiometabolite entering the brain.

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