Distribution volume ratios without blood sampling from graphical analysis of PET data.
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.
Logan
J
J
Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Fowler
J S
JS
Volkow
N D
ND
Wang
G J
GJ
Ding
Y S
YS
Alexoff
D L
DL
D001479:Basal Ganglia / Q000378:metabolism; D001800:Blood Specimen Collection; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008774:Methylphenidate / Q000378:metabolism; D009419:Nerve Tissue Proteins; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D008774:Methylphenidate; D020891:Raclopride