| Project/Area Number |
01470143
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
YOKOYAMA Akira Kyoto University, Fac. Pharmaceu-Sciences, Professor, 薬学部, 教授 (90025685)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIBAYASHI Yasuhisa Kyoto University, School of Medicine, Assistant Professor, 医学部, 助手 (50165411)
ENDO Keigo Kyoto University, School of Medicine, Associate Professor, 医学部, 助教授 (10115800)
AKABOSHI Mitsuhiko Kyoto University, Nuclear Reactor Laboratory, Associate Professor, 原子炉実験所, 助教授 (00027418)
ARANO Yasushi Kyoto University, Fac, Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (90151167)
HORIUCHI KAZUKO (SUZUKI KAZUKO) Kyoto University, Fac, Pharmaceutical Sciences, Assistant Professor., 薬学部, 助手 (50144382)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | 99m-Tc Labeled Antitumor Antibody / 186-Re Labeled Antitumor Antibody / Nuclear Medicine Tumor Diagnosis / Nuclear Medicine Tumor Therapy / 99m-Tc-Dimercaptosuccinic Acid Complex / Polynuclear Metal Complex / Biodistribution / がんの核医学診断 / がんの核医学治療 / 多核錯体 / 99m-Tc標識抗腫瘍抗体 / 186-Re標識抗腫瘍抗体 / 99m-Tcジメルカプトコハク酸錯体 |
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| Research Abstract |
The aim of the present work is the development of new 99m-Tc radiolabeled antitumor antibody for diagnostic use in Nuclear Medicine. Exploitation of previously found character of the polynuclear 99m-Tc complex of Dimercaptosuccinic acid (Tc-DMS) to accumulate in tumor cells was estimated as providing the basis to be associated with the tumor targetting function of antibodies.
At first, fundamental aspects needed in radiolabeled antibody were screened. The distinctive chemical character of the polynuclear Tc-DMS complex related with its stability in blood and its tumor accumulation were studied. Of particular interest was the effect of the environment on the injected Tc-DMS ; namely, the role of dilution on the dissociation of some 20-30% of the coordinated ligands, while the polynuclear state of Tc remained stable. Moreover, after this partial dissociation, the polynucleated Tc complex became pH sensitive ; in the in-vitro cell experimental, dramatic tumor cell radio activity increase of dissociated TcO_4^<-3> species took place, as the pH changed from neutral to the acidic region. On the other hand, in tumor tissue, low cell surrounding pH has been reported ; thus, the dilution related complex dissociation phenomenon has been demonstrated as holding the key for the very peculiar Tc-DMS behavior in-vivo.
The next task was the establishment of the basis required in antibodies holding the polynuclear Tc-DMS complex structure as the radiolabeled site. In this work, a conjugate of the ligand DMS with an antibody molecule (IgG) using the heterofunctional cross linker reagent N- (maleimidocaproyloxy) succinimide was synthesized and radiolabeled. The very preliminar data offered promising results ; so, it is understood that future research on therapeutical 186-Re labeling might be also feasible.
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