Central in vivo nicotinic acetylcholine receptor imaging agents for positron emission tomography (PET) and single photon emission computed tomography (SPECT). 2009

Mikako Ogawa, and Hideo Tsukada, and Kentaro Hatano, and Yasuomi Ouchi, and Hideo Saji, and Yasuhiro Magata
Photon Medical Research Center, Hamamatsu University School of Medicine, Japan.

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are useful for non-invasive investigation of brain receptors. With these imaging techniques, changes in brain receptor densities and distributions during chronic drug treatments and disease progressions can be tracked for a long period. Appropriate radiolabeled imaging agents are necessary for PET and SPECT molecular imaging. Nicotinic acetylcholine receptors (nAChRs) play important roles in brain functions. The alpha4beta2 and alpha7 are the major nAChR subtypes in the brain. To date, several subtype selective radiolabeled ligands for nAChR have been reported. For the alpha4beta2 subtype, some agents are already applied for human studies, but only a few agents are developed for the alpha7 subtype. Here, we overview our results of [(125/123)I]5-iodo-3-(2(S)-azetidinylmethoxy)pyridine and 5-[11C]methyl-3-(2-(S)-azetidinylmethoxy)pyridine ([11C]5MA) for alpha4beta2 subtype imaging, and [11C](R)-2-methylamino-benzoic acid 1-aza-bicyclo[2.2.2]oct-3-yl ester ([11C](R)-MeQAA) for alpha7 subtype imaging.

UI MeSH Term Description Entries
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D011978 Receptors, Nicotinic One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors. Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001384 Azetidines
D015899 Tomography, Emission-Computed, Single-Photon A method of computed tomography that uses radionuclides which emit a single photon of a given energy. The camera is rotated 180 or 360 degrees around the patient to capture images at multiple positions along the arc. The computer is then used to reconstruct the transaxial, sagittal, and coronal images from the 3-dimensional distribution of radionuclides in the organ. The advantages of SPECT are that it can be used to observe biochemical and physiological processes as well as size and volume of the organ. The disadvantage is that, unlike positron-emission tomography where the positron-electron annihilation results in the emission of 2 photons at 180 degrees from each other, SPECT requires physical collimation to line up the photons, which results in the loss of many available photons and hence degrades the image. CAT Scan, Single-Photon Emission,CT Scan, Single-Photon Emission,Radionuclide Tomography, Single-Photon Emission-Computed,SPECT,Single-Photon Emission-Computed Tomography,Tomography, Single-Photon, Emission-Computed,Single-Photon Emission CT Scan,Single-Photon Emission Computer-Assisted Tomography,Single-Photon Emission Computerized Tomography,CAT Scan, Single Photon Emission,CT Scan, Single Photon Emission,Emission-Computed Tomography, Single-Photon,Radionuclide Tomography, Single Photon Emission Computed,Single Photon Emission CT Scan,Single Photon Emission Computed Tomography,Single Photon Emission Computer Assisted Tomography,Single Photon Emission Computerized Tomography,Tomography, Single-Photon Emission-Computed
D049268 Positron-Emission Tomography An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower. PET Imaging,PET Scan,Positron-Emission Tomography Imaging,Tomography, Positron-Emission,Imaging, PET,Imaging, Positron-Emission Tomography,PET Imagings,PET Scans,Positron Emission Tomography,Positron Emission Tomography Imaging,Positron-Emission Tomography Imagings,Scan, PET,Tomography Imaging, Positron-Emission,Tomography, Positron Emission
D019275 Radiopharmaceuticals Compounds that are used in medicine as sources of radiation for radiotherapy and for diagnostic purposes. They have numerous uses in research and industry. (Martindale, The Extra Pharmacopoeia, 30th ed, p1161) Radiopharmaceutical

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