2004 Fiscal Year Final Research Report Summary
Molecular design of radioiodinated peptides for targeted radiotherapy
| Project/Area Number |
14370270
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Chiba University |
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Principal Investigator |
ARANO Yasushi Chiba University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (90151167)
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| Co-Investigator(Kenkyū-buntansha) |
UEHARA Tomoya Chiba University, Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学研究院, 助手 (10323403)
ENDO Keigo Gunma University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10115800)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Radiotherapy / antibody fragment / radioiodine / kidney / brush border membrane / metabolizable linkage / peptides |
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| Research Abstract |
The effect of amino acid sequence of radioiodination reagents on recognition by renal brush border membrane was investigated. L-Lysine in 3'0iodohippuryl-N^ε-maleoyl-L-lysine3'-Iodohippuryl-N^ε-maleoyl-L-lysine (HML) was replaced with L-aspartic acid, L-phenylalanine, L-tyrosine to prepare respective low molecular weight substrates. All of the three substrate liberated m-iodohippuric acid while incubated in the presence of brush membrane vesicles prepared from rat kidney cortex. The highest release of m-iodohippuric acid was observed with glycyl-tyrosine sequence, and the release of m-iodohippuric acid was significantly inhibited by the presence of cilastatin, a well-known inhibitor for renal dipeptidase. After converting the hydroxy group of tyrosine to maleimide group, the compound was radioiodinated and conjugated to Fab fragments. In biodistribution studies in mice, the new radiolabeling reagent-conjugated Fab registered renal radioactivity levels as low as those observed with HWL-conjugated Fab fragments. these findings indicates that enzymes on renal brush border membrane recognize a variety of peptide linkages. Such characteristics of the enzymes on renal brush border membrane render further appliation of the present molecular design feasible to a variety of radionuclides including modified iodobenzoate and metallic redionuclides such as ^<90>Y, ^<111>In, ^<99m>Tc and ^<186/188>Re.
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