| Project/Area Number |
04557049
|
|---|
| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Radiation science
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
FUJIBAYASHI Yasuhisa Kyoto University, Department of Genetic Biochemistty, Associate Professor, 薬学部, 助教授 (50165411)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Junichi Nihon-Medi-physics, Co.Ltd., Research and Development Center, Director., 研究開発本部, 研究部長
SAKAHARA Harumi Kyoto University, Faculty of Medicine, Department of Nuclear Medicine, Lecturer, 医学部, 講師 (10187031)
HORIUCHI Kazuko Kyoto university, Faculty of Pharmaceutical Sciences, Department of Radiopharmac, 薬学部, 助手 (50144382)
吉川 淳一 日本メジフィジックス(株), 研究開発本部, 研究部長
葉杖 正昭 日本メジフィジックス(株), 研究開発本部長
|
|---|
| Project Period (FY) |
1992 – 1994
|
| Project Status |
Completed (Fiscal Year 1994)
|
| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥4,600,000 (Direct Cost: ¥4,600,000)
|
|---|
| Keywords | radioimmunoassay / high specific activity / metal label / gallium / Indium / antisense oligonucleotide / antibody / digoxin / 高感度 / ガリウム-67 / 銅-62 |
|---|
| Research Abstract |
To achieve higher sensitivity in the detection of biologically active substances (ca..antibodies, drugs, antisense oligonucleotides, etc.) and lessen radioactive waste disposal, short-lived gamma emitting metal radionuclide was attached to such molecules. Gallium-67(Ga-67, half life=78hr)or indium-111 (In-111, half life=2.8day) was selected as a metalradionuclide and biologically active substances conjugated with deferoxamine, diethylenetriamine-pentaacetic acid or isothiocyanobenzyl-EDTA were radiolabeled.
(1) Antibody : monoclonal anti-human growth hormone (GH) antibody was conjugated with deferoxiamine (DF) through dialdehyde-starch polymer spacer and labeled with Ga-67. Using this Ga-67-anti-GH antibody, immunoradiometric assay with 10 times higher sensitivity could be realized.
(2) Drug : digoxin, a cardiac glycoside requireing therapeutic drug monitoring, was labeled with Ga-67 using DF as a bifunctional chelating agent. Ga-67-DF-digoxin has similar affinity to anti-digoxin antibody as well as Na, K-ATPase. Using the Ga-67-DF-digoxin, digoxin-RIA as well as myocardial Na, K-ATPase imaging in vivo.were successfully performed.
3) Antisense oligonucleotide : Antisense oligonucleotide against human c-erbB-2 was 5'-aminated and conjugated with isothiocyanobenzyl-EDTA (IBE) and labeled with In-111. In-111-IBE-oligonucleotide showed high stability even in human serum, an indication of possible in-vivo application. In fact, biodistribution study in nude mice bearing c-erbB2 mRNA (+) tumor indicated the sequence selective tumor localization.
It was concluded that short-lived metal radionuclide can be used not only for in vivo nuclear medicine, but in vitro diagnosis as well as basic research studies.
|
