PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.
[18F]altanserin has been used to label serotonin 5-HT2A receptors, which are believed to be important in the pathophysiology of schizophrenia and depression. The purpose of this study was to test the feasibility of a constant infusion paradigm for equilibrium modeling of [18F]altanserin with PET. Kinetic modeling with [18F]altanserin may be hampered by the presence of lipophilic radiometabolites observed in plasma after intravenous administration.


METHODS
Eight healthy volunteers were injected with [18F]altanserin as a bolus (208+/-9 MBq [5.62+/-0.25 mCi]) plus constant infusion (65+/-3 MBq/h [1.76+/-0.08 mCi/h]) ranging from 555 to 626 min (615+/-24 min) after injection. PET acquisitions (10-20 min) and venous blood sampling were performed every 30-60 min throughout the infusion period.


RESULTS
Linear regression analysis revealed that time-activity curves for both brain activity and plasma [18F]altanserin and metabolite concentrations stabilized after about 6 h. This permitted equilibrium modeling and estimation of V3' (ratio of specific uptake [cortical-cerebellar] to total plasma parent concentration after 6 h). Values of V3' ranged from 1.57+/-0.38 for anterior cingulate cortex to 1.02+/-0.39 for frontal cortex. The binding potential V3 (ratio of specific uptake to free plasma parent concentration after 6 h, using group mean f1) was also calculated and ranged from 169+/-41 for anterior cingulate cortex to 110+/-42 for frontal cortex. From 6 h onward, the rate of change for V3' and V3 was only 1.11+/-1.69 %/h.


CONCLUSIONS
These results demonstrate the feasibility of equilibrium imaging with [18F]altanserin over more than 5 radioactive half-lives and suggest a method to overcome difficulties associated with lipophilic radiolabeled metabolites. The stability in V3 and V3' once equilibrium is achieved suggests that a single PET acquisition obtained at 6 h may provide a reasonable measure of 5-HT2A receptor density.
van Dyck
C H
CH
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Tan
P Z
PZ
Baldwin
R M
RM
Amici
L A
LA
Garg
P K
PK
Ng
C K
CK
Soufer
R
R
Charney
D S
DS
Innis
R B
RB
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D007650:Ketanserin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016014:Linear Models; D008297:Male; D011985:Receptors, Serotonin / Q000032:analysis*; D013997:Time Factors; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D011985:Receptors, Serotonin; C071983:altanserin; D007650:Ketanserin