Determination of receptor occupancy in the presence of mass dose: [¹¹C]GSK189254 PET imaging of histamine H₃ receptor occupancy by PF-03654746.

ABSTRACT: Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds "tracer" levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant K_d of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo K_d. This method was applied in a study of healthy human subjects with the histamine H₃ receptor radioligand [¹¹C]GSK189254 to measure the PK-occupancy relationship of the H₃ antagoni

SUBMITTER: Gallezot JD 

PROVIDER: S-EPMC5363483 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature