@article{oai:repo.qst.go.jp:00045107,
 author = {Hanaoka, Hirofumi and Mukai, Takahiro and Habashita, Sayo and Asano, Daigo and Ogawa, Kazuma and Kuroda, Yoshihiro and Akizawa, Hiromichi and IIda, Yasuhiko and Endou, Keigo and Saga, Tsuneo and Saji, Hideo and 秋澤 宏行 and 遠藤 啓吾 and 佐賀 恒夫},
 issue = {5},
 journal = {Nuclear Medicine and Biology},
 month = {Jul},
 note = {Since elevated levels of gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] are associated with a poor prognosis in cancer patients, these enzymes are potential targets for tumor imaging. In the present study, a cyclic decapeptide, cCTTHWGFTLC (CTT), was selected as a mother compound because of its selective inhibitory activity toward gelatinases. For imaging gelatinase activity in tumors, we designed a CTT-based radiopharmaceutical taking into consideration that (1) the HWGF motif of the peptide is important for the activity, (2) hydrophilic radiolabeled peptides show low-level accumulation in the liver and (3) an increase in the negative charge of radiolabeled peptides is effective in reducing renal accumulation. Thus, a highly hydrophilic and negatively charged radiolabel, indiun-111-diethylenetriaminepentaacetic acid ((111)In-DTPA), was attached to an N-terminal residue distant from the HWGF motif ((111)In-DTPA-CTT). In MMP-2 inhibition assays, In-DTPA-CTT significantly inhibited the proteolytic activity in a concentration-dependent fashion. When injected into normal mice, (111)In-DTPA-CTT showed low levels of radioactivity in the liver and kidney. A comparison of the pharmacokinetic characteristics of (111)In-DTPA-CTT with those of other CTT derivatives having different physicochemical properties revealed that the increase in hydrophilicity and negative charge caused by the conjugation of (111)In-DTPA reduced levels of radioactivity in the liver and kidney. In tumor-bearing mice, a significant correlation was observed between the accumulation in the tumor as well as tumor-to-blood ratio of (111)In-DTPA-CTT and gelatinase activity. These findings support the validity of the chemical design of (111)In-DTPA-CTT for reducing accumulation in nontarget tissues and maintaining the inhibitory activity of the mother compound. Furthermore, (111)In-DTPA-CTT derivatives would be potential radiopharmaceuticals for the imaging of gelatinase activity in metastatic tumors in vivo.},
 pages = {503--510},
 title = {Chemical design of a radiolabeled gelatinase inhibitor peptide for the imaging of gelatinase activity in tumors.},
 volume = {34},
 year = {2007}
}