PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.

Abstract

UNLABELLED:

[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.

CONCLUSION:

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.

• Authors: C H van Dyck, P Z Tan, R M Baldwin, L A Amici, P K Garg, C K Ng, R Soufer, D S Charney, R B Innis
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 41 Issue 2 Pg. 234-41 (Feb 2000) ISSN: 0161-5505 [Print] United States
• PMID: 10688105 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fluorine Radioisotopes
• Receptors, Serotonin
• altanserin
• Ketanserin

Topics

• Adult
• Brain (diagnostic imaging, metabolism)
• Feasibility Studies
• Female
• Fluorine Radioisotopes
• Humans
• Image Processing, Computer-Assisted
• Infusions, Intravenous
• Ketanserin (administration & dosage, analogs & derivatives)
• Linear Models
• Male
• Receptors, Serotonin (analysis)
• Time Factors
• Tomography, Emission-Computed