The radioligand [carbonyl-11C]WAY-100635 (11C-WAY) is a PET tracer of the serotonin 5HT1A receptors in the human brain. It is metabolized so rapidly in the circulation that it behaves more as a chemical microsphere than as a tracer subject to continuous exchange between the circulation and brain tissue. Although reference tissue methods are useful as analyses of uptake of some radioligands with indeterminate arterial input functions, their use to analyze 11C-WAY uptake and binding is challenged by the rapid plasma metabolism, which violates the assumption that regions of interest and reference regions continue to exchange radioligand with the circulation during the entire uptake period. Here, we proposed a method of calculation (Hypotime) that specifically uses the washout rather than the accumulation of 11C-WAY to determine binding potentials (BP ND), without the use of regression analysis. Methods: A total of 19 healthy volunteers (age range, 23-73 y) underwent PET to test the Hypotime application of the chemical microsphere properties of 11C-WAY to identify regions of binding and nonbinding on the exclusive basis of the rate of washout of 11C-WAY. Results: The results of the Hypotime method were compared with the simplified but multilinearized reference tissue method (MLSRTM). The distribution of receptor BPND obtained with Hypotime was consistent with previous autoradiography of postmortem brain tissue, with the highest values of BPND recorded in the medial temporal lobe and decline of receptor availability with age. The values in the basal ganglia and cerebellum were negligible. The MLSRTM, in contrast, yielded lower BP ND in all regions and only weakly revealed the decline with age. Conclusion: The simple and computationally efficient Hypotime method gave reliable values of BPND without the use of regression. The MLSRTM, on the other hand, appeared to be affected by the early disappearance of the radioligand from the circulation and the associated uncertain late presence of 11C-WAY in the circulation.
- Serotonin 5HT receptors
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging