In order to perform accurate pharmacokinetic modeling of dynamic PET data, a number of measurements need to be obtained with high accuracy; in particular, the time course of Selleckchem Proteasome inhibitor the concentration of the radiotracer in a vessel feeding the ROI (the so-called

arterial input function or AIF) is required. Unfortunately, characterizing the AIF in a typical PET scan is challenging due to both the limited spatial resolution and the lack of available anatomical landmarks to define an arterial ROI. The resolution of a PET scanner is mainly determined by the physical size and disposition of the radiation detectors. In clinical PET scanners, this resolution, as measured by the full-width at half maximum of the point spread function of the scanner, is approximately 4 to 5 mm [60] and [61]. This limited spatial resolution leads to the well-known partial volume effect (PVE), whereby the quantification of tracer uptake within a particular ROI is compromised by both activity spilling in from and out to adjacent tissues. The degree to which the PVE results in inaccuracy in estimating the concentration of tracer in a particular ROI depends on both the size of the ROI and the relative tracer activity between the ROI and the surrounding tissues [62] and [63]. For example, the PVE will lead to an overestimation of tracer uptake in an ROI surrounded by tissues with higher tracer uptake

and an underestimation when the ROI is surrounded by tissues with lower uptake values.

In particular, it has been Venetoclax supplier shown that PVE is negligible for regions with homogeneous uptake bigger than two to three times the spatial resolution of the scanner [62]. Thus, on most clinical scanners, quantification of ROIs smaller than 10–15 mm in any one dimension will be significantly affected by PVE. Given the small size of the vast majority of the arteries (< 10–15 mm) available within a typical FOV, the PVE represents a considerable barrier to accurate image-based AIF characterization. The PET community has explored two main approaches to overcome the difficulty of characterizing the AIF for applications in oncology: obtaining blood samples Protirelin from a peripheral vessel and deriving the time course from the blood pool of the left ventricle. For the former, arterial samples are taken at regular time intervals (defined according to the needs and specifications of the pharmacokinetics of the radiotracer), and radioactivity is determined in a gamma well counter to derive the radiotracer concentration in the blood at the time of sampling. This approach has the obvious advantage of being able to provide very accurate quantification of the AIF (see, e.g., Refs. [64] and [65]). For applications in which the heart is contained within the FOV, the AIF can be estimated by placing an ROI inside the left ventricle which is sufficiently large to minimize the PVE. However, these two common solutions suffer from fundamental limitations.