Mapping of Histamine H₁ Receptors in the Human Brain Using [¹¹C]Pyrilamine and Positron Emission Tomography

We have studied the characteristics of carbon‐11 labeled pyrilamine as a radioligand for investigating histamine H₁ receptors in human brain with positron emission tomography (PET). [¹¹QPyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45–60 min), ¹¹C radioactivity was observed at high concentrations in the frontal and temporal cortex, hippocampus, and thalamus, and at low concentrations in the cerebellum and pons. The regional distribution of the carbon‐11 labeled compound in the brain corresponded well with that of the histamine H₁ receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 ± 0.071. Intravenous administration of d‐chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 ±0.015). The availability of this method for measuring histamine H₁ receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H₁ receptors are thought to be abnormal.