Development of Molecular Imaging and its Application to Medical Science

Kazuhiko Yanai
Professor
Department of Pharmacology, Graduate School of Medicine

Our group is dedicated to conducting basic and clinical research, of the highest quality, originality, and creativity, on molecular PET imaging and the medical applications of PIXE. Our division is conducting the following basic and clinical studies:

1.PET imaging of specific neurotransmission in the human brain (Figs. 1, 2, 3)

Neuroimaging is a powerful, innovative tool for studying the pathology of psychiatric and neurological diseases and, more recently, for assessing the efficacy of drug treatment. Technological advances in imaging have made it possible to extract information from the human brain regarding a drug's mechanism and site of action, non-invasively. Until now, our understanding of human brain pharmacology has depended primarily on indirect assessments or models derived from animal studies. However, the advent of multiple techniques for human brain imaging has allowed researchers to focus directly on human pharmacology and brain function. In this project, we will first develop labeling methods, using radiopharmaceuticals and kinetic modeling, to measure specific neurotransmission, in order to investigate the functions of neurotransmission non-invasively. Simultaneously, we will apply PET techniques to examine the functions of specific neurotransmissions in the living human brain. PET images of dopamine D2 and histamine H1 receptors in living human brains are shown in Fig. 1. In particular, the animal PET camera will be indispensable for developing new PET imaging techniques.

2.Functional neuroanatomy of subjective feelings using 3D-PET(Fig. 4)

One of the most exciting methodological advances for brain research has been in functional brain imaging, which enables the localization and characterization of neural activity in the living human brain. Recently developed 3D-PET imaging techniques using H₂¹⁵O and¹⁸F-FDG make it possible to visualize the brain activity associated with cognitive processes. We will visualize functional neuroanatomy of subjective feelings of sleepiness, visceral perception, itching, and emotion using H₂¹⁵O.

3.Application of PIXE to medical science

PIXE is a unique method for quantifying heavy elements precisely. So far, this extraordinary method has had only limited use in the field of medicine. Our group will develop new applications of PIXE for the medical sciences. Micro and macro PIXE methods will be used to study the secretory mechanisms of cells and for regional brain imaging of the elements in several pathological conditions, respectively.

Fig. 1: Our automated synthesis system for producing¹¹C-labeled ligands. Using this system, we are examining specific neurotransmission in the living human brain.

Fig. 2:¹¹C-Labeled ligands developed at Tohoku University.¹¹C-Labeled raclopride, doxepin, and donepezil are used for imaging dopamine D2 receptors, histamine H1 receptors, and acetylcholinesterase, respectively.

Fig. 3: PET visualization of specific dopamine D2 and histamine H1 receptors in the living human brain.

Fig. 4: The subjective feeling of "sleepiness" can be imaged using 3D-PET and H₂¹⁵O. Sleepiness can be induced by administering sedative antihistamines while performing a spatial cognition task. Some areas are deactivated and others are activated during sleepiness caused by antihistamines.