Elsevier

Nuclear Medicine and Biology

Volume 31, Issue 8, November 2004, Pages 1005-1011
Nuclear Medicine and Biology

Simplified PET measurement for evaluating histamine H1 receptors in human brains using [11C]doxepin

https://doi.org/10.1016/j.nucmedbio.2004.06.009Get rights and content

Abstract

The aim of this study was to develop simplified positron emission tomography measurement using [11C]doxepin ([11C]DOX) to evaluate histamine H1 receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [11C]DOX, estimated quantitatively with a two-compartment model, and the [11C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [11C]DOX–H1R binding.

Introduction

The histamine system plays important roles in cortical activation and cognitive and behavioral processing, mainly through the histamine H1 receptors (H1Rs) [1], [2], [3], [4], [5], [6], [7]. In addition, the H1R is associated with neurological diseases such as Alzheimer's disease (AD) and epilepsy [8], [9]. These previous studies imply that understanding the histaminergic system in the central nervous system (CNS) is physiologically and clinically important. Recently, receptor imaging using positron emission tomography (PET) with [11C]doxepin ([11C]DOX) was developed to evaluate H1R in the living human brain [10], [11], and provided direct evidence for the physiological function of histamine and abnormalities of the H1R in patients with AD and epileptic patients [10], [12], [13], [14]. Therefore, it is considered that the mapping of H1Rs using PET provides a strong tool for clarifying the functions of H1Rs in the CNS. However, in the quantitative PET measurement of H1Rs we have been obliged to cannulate the subject's radial artery, to allow sampling of arterial blood, and to have subjects remain with their head fixed in a PET camera for 90 min. Experiments of such long duration cause patients and other volunteers mental and physical stress, and such a protocol is not suitable for some categories of patients. There are several simplified methods for quantitative evaluation of receptor density in human brains using PET, such as the reference tissue model and graphical analysis without blood sampling [15], [16]. These methods can eliminate the arterial blood sampling but do not shorten the duration of the PET scan. In the present study, we propose a simplified method for quantifying H1Rs using PET and [11C]DOX. The method consists of a static PET scan and arterial blood sampling at a single time point.

Section snippets

Subjects

Five male volunteers, 21–27 years of age and weighing 44–67 kg, were recruited for this study. No subjects were on medication or had any history of psychiatric disorders. No anatomical abnormalities were found in the MRI images. Subjects were asked to abstain from medication for a week before their study. Written informed consent was obtained from all subjects. The study was approved by the Ethics Committees of the Tokyo Metropolitan Institute of Gerontology and the Tohoku University School of

Correlation between DV and SUV

The correlation coefficients between DV and all SUVs investigated, every 10- and 20-min static scan, were low for all intervals of PET scan (−0.30<r<0.37), although they became larger in the later stage.

Correlation between DV and NUVAUP

The correlation coefficient between DV and NUVAUC became larger with time and reached a plateau between 60 and 90 min, where no difference was found between the 10- and 20-min scans (Fig. 2).

Correlation between AUC0–t and plasma radioactivity

The correlation coefficient between AUC0–t and each arterial blood sampling time is summarized in Table 1

Discussion

In this study, we developed a simplified static PET measurement for evaluation of H1Rs using PET and [11C]DOX and using DV estimated with a two-compartment model as a standard [18]. Yanai et al. reported that the distribution of [11C]DOX in PET images in the later stages of the scan reflected the distribution of H1R in the brain [11].

First, we examined the correlation between DV and SUV. SUV is the uptake value normalized for the injected dose and body weight, and is often used for quantitative

Acknowledgments

This work was partly supported by grants-in-aid from the Japan Society for the Promotion of Science and a 21st Century COE Program (Bio-nano-technology) from the Ministry of Education, Science, Sports and Culture, Japan, and the Ministry of Health, Labour and Welfare, Japan. The authors thank the volunteers in the PET measurement, Ms. Miyoko Ando for care of subjects and Dr. Kazunori Kawamura for the preparation of [11C]DOX.

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