| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
It is very important to evaluate a receptor binding affinity of novel neuro-functional radiopharmaceuticals accurately when we are developing these compounds. Currently we usually measure the affinity of them with radio-receptor assay, using receptor preparation removed from living tissue, but structure of the receptor may be different from its natural state because the receptor was under in vitro condition. For the purpose of evaluating the affinity of these developing pharmaceuticals, easy, quick and accurate procedure is desirable in screening test. In this study, we tried to put on a new method which can evaluate the receptor binding affinity by keeping the condition like under living body. We will compare the affinity measured from new method with those measured from conventional in vivo and in vitro methods. First, we developed a new radiopharmaceutical for comparing and evaluating the affinity. Nicotinic acetylcholine receptors (nAChRs) are implicated in various brain functions, such as cognition and memory, so we synthesized a derivative of 3-(2-(S)-azetidinylmethoxy) pyridine (A-85380), 5IA, and its binding property in vivo are evaluated. From our experimental data, 5IA has high affinity to nAChRs in vivo and we can easily measure the binding property in vivo and in vitro. In next experiment, we synthesized [^<11>C]DASB, which show selective binding to serotonin trans porter (SERT), and evaluated its binding property in vivo in normal control and patients of neuro-degenerative diseases by PET. From this study, [^<11>C]DASB has great potential for in vivo PET imaging of SERT and we will be able to compare the affinity with those from in vivo and in vitro assay.
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