Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data

Abstract

The distribution volume ratio (DVR), which is a linear function of receptor availability, is widely used as a model parameter in imaging studies. The DVR corresponds to the ratio of the DV of a receptor-containing region to a nonreceptor region and generally requires the measurement of an arterial input function. Here we propose a graphical method for determining the DVR that does not require blood sampling. This method uses data from a nonreceptor region with an average tissue-to-plasma efflux constant k2 to approximate the plasma integral. Data from positron emission tomography studies with [11C]raclopride (n = 20) and [11C]d-threo-methylphenidate ([11C]dMP) (n = 8) in which plasma data were taken and used to compare results from two graphical methods, one that uses plasma data and one that does not. k2 was 0.163 and 0.051 min-1 for [11C]raclopride and [11C]dMP, respectively. Results from both methods were very similar, and the average percentage difference between the methods was -0.11% for [11C]raclopride and 0.46% for [11C]dMP for DVR of basal ganglia (BG) to cerebellum (CB). Good agreement between the two methods was also achieved for DVR images created by both methods. This technique provides an alternative method of analysis not requiring blood sampling that gives equivalent results for the two ligands studied. It requires initial studies with blood sampling to determine the average kinetic constant and to test applicability. In some cases, it may be possible to neglect the k2 term if the BG/CB ratio becomes reasonably constant for a sufficiently long period of time over the course of the experiment.

Evaluation of Four Pyridine Analogs to Characterize 6-OHDA-Induced Modulation of mGluR5 Function in Rat Brain Using microPET Studies

“…Rapid changes in the accumulation of the activity in small brain areas create significant fluctuation of data and cause difficulties in direct mathematical fitting using a three-compartment model. For that reason, we developed a modified graphical model of the Logan method for data analysis (Logan et al, 1990(Logan et al, , 1996Logan, 2000). To increase the accuracy of the outcome measures from the same rat, we used cerebellum as a reference tissue, as the selection of the region is repeatable; based on in situ hybridization histochemical and immunohistochemical studies, adult rat brain has only weak expression of mGluR5 in Golgi cells and cerebellar nuclei in the cerebellum (Shigemoto and Mizuno, 2000).…”

“…The severity of the lesion was determined by PET imaging of DA transporter binding using [ 11 C]CFT, a selective and sensitive ligand for DA transporter (Brownell et al, 1996). After PET imaging with mGluR5 ligands and [ 11 C]CFT binding potential images were processed using a modified graphical method of Logan (Logan et al, 1990(Logan et al, , 1996Logan, 2000). In addition, representative regions of interests (ROIs) were drawn to the left and right brain areas on the original images of activity distribution.…”

Evaluation of Dopamine D-2 Receptor Occupancy by Clozapine, Risperidone, and Haloperidol In Vivo in the Rodent and Nonhuman Primate Brain Using 18F-Fallypride

“…This index was measured by using the distribution volume method (DV) of 18 F-fallypride in each brain region (Logan et al 1990) as well as the distribution volume ratio method (DVR) using the cerebellum as a reference region (Logan et al 1996) and are described below.…”

“…Method B: Distribution Volume Ratio (DVR) (Logan et al 1996). As with the DV method, this is also a multiple time graphic method that yields a parameter, DVR, that is proportional to specific binding.…”

“…As with the DV method, this is also a multiple time graphic method that yields a parameter, DVR, that is proportional to specific binding. The DVR method differs from the DV method in that the reference region is incorporated rather than the arterial blood radioligand concentration (Logan et al 1996). The implementation of this method to 18 F-fallypride was previously described.…”