成果報告書詳細
管理番号20110000001719
タイトル*平成22年度中間年報 「がん超早期診断・治療機器の総合研究開発/超早期高精度診断システムの研究開発:画像診断システムの研究開発/がんの性状をとらえる分子プローブ等の研究開発(がんの特性識別型分子プローブ)」(国立大学法人京都大学)
公開日2012/9/11
報告書年度2010 - 2010
委託先名国立大学法人京都大学
プロジェクト番号P10003
部署名バイオテクノロジー・医療技術部
和文要約和文要約等以下本編抜粋:1. 研究開発の内容及び成果等
(1) 乳がんを標的とした分子プローブ開発
分子標的治療が確立しており治療効果予測に基づくテーラーメード医療が期待されるがんとして乳がんを選択し、分子プローブ開発を行った。具体的には、エストロゲン受容体(ER)、ヒト上皮成長因子受容体(HER2)、膜結合型マトリクスメタロプロテアーゼ-1(MT1-MMP)を標的分子とする分子プローブの設計・合成を行った。その結果、高い標的親和性を有する抗HER2単鎖抗体、抗MT1-MMP単鎖抗体を得ることに成功した。また、標識化した抗MT1-MMP単鎖抗体およびペプチドプローブについて、皮下移植担がんマウスを用いたインビボ検討を行ったところ、腫瘍部位に高い集積性を認めた。
英文要約(1) Development of molecular imaging probes targeting breast cancer
A molecularly targeted approach has already been established for breast cancer treatment. There is an increased expectation for personalized medicine for breast cancer based on prediction of its therapeutic effects. We developed molecular probes for breast cancer. That is, we designed and synthesized molecular probes targeting estrogen receptor (ER), human epidermal growth factor receptor (HER2), and membrane type-1 matrix metalloproteinase (MT-1 MMP). Anti-HER2 single chain antibody and anti-MT1-MMT single chain antibody were successfully prepared. Labeled anti-MT1-MMT single chain antibody and peptide probe were examined in vivo using mice bearing subcutaneously implanted cancer, resulting in high accumulations observed in tumor.
(2) Development of molecular imaging probes targeting prostate cancer
A treatment strategy for prostate cancer is determined based on risk assessment. We developed molecular probes for prostate cancer. That is, we designed a low molecular weight probe targeting prostate-specific membrane antigen (PSMA). This probe is expected to have better biokinetics compared to existing probes. We successfully synthesized target compounds, control compounds, and labeled compounds. Two types of cancer cells were obtained that were promising as evaluation systems for PSMA probes. We were able to prepare animals bearing subcutaneously implanted cancer.
(3) Development of molecular imaging probes targeting pancreatic cancer
Due to the asymptomatic onset of pancreatic cancer, most patients are in advanced or metastatic condition at the time of diagnosis, resulting in poor prognosis. Earlier diagnosis and better treatments are urgently needed to improve the survival rate of pancreatic cancer. Thus, we developed molecular probes for the early detection of pancreatic cancer. That is, we designed and synthesized molecular probes targeting integrin αVβ6, which was involved in tumor progression, for pancreatic ductal carcinoma and targeting somatostatin receptor for pancreatic endocrine tumor. For the integrin probe, a peptide probe was successfully synthesized and labeled. An in vivo examination was performed using mice bearing subcutaneously implanted cancer, and a higher accumulation of the probe was observed in αVβ6-positive tumor than αVβ6-negative tumor. For the somatostatin receptor probe, a method for synthesizing 68Ga-DOTATOC was established.
(4) Development of molecular imaging probes targeting hypoxic environment in cancer regions
In various types of solid tumors, hypoxia develops as abnormal proliferation outstrips the blood supply. Because this hypoxic region is involved in tumor malignancy, we developed molecular probes for hypoxic environments. That is, we designed and synthesized molecular probes targeting hypoxia-inducible factor-1 (HIF-1)-active regions that imply biologically hypoxic regions. A low-molecular-weight probe which existed stable in such regions was successfully synthesized and labeled. We also successfully radiolabeled another probe which was a derivative of the HIF-1 binding low-molecular-weight compound and performed in vivo examination using mice bearing subcutaneously implanted cancer. A high accumulation of probe was observed in the tumor.
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