成果報告書詳細
管理番号20120000001207
タイトル*平成23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)」
公開日2014/6/14
報告書年度2011 - 2011
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
英文要約(1) 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 and GLP-1 receptor for pancreatic endocrine tumor.

・ For the integrin probe, a radioiodinated peptide probe (123I-IFMDV2) was successfully synthesized. The examinations performed in vitro and in vivo revealed the affinity and specificity of 123I-IFMDV2 to integrin αVβ6.
・ For the somatostatin receptor probe, 68Ga-DOTATOC was successfully synthesized. Microwave-assisted, efficient labeling method for 68Ga-DOTATOC synthesis was also established.
・ For the GLP-1 receptor probe, [123I]IB12-Ex(9-39), an Exendin (9-39) derivative probe, was synthesized. An in vivo imaging study using mice bearing subcutaneously implanted cancer brought a clear SPECT image of insulinoma.

(2) 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. Thus, 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).

・ For the ER probe, 18F-FES was successfully synthesized.
・ For the HER2 probe, 111In-anti-HER2 diabody was successfully obtained. An in vivo biodistribution study showed high accumulation in tumors.
・ For the MT1-MMP probe, 111In-anti-MT1-MMP diabody was successfully obtained. An in vivo biodistribution study showed high accumulation in tumors.

(3) 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.

・ For the PSMA probe, an unsymmetrical urea probe was successfully synthesized. An in vivo imaging study brought a clear SPECT image of PSMA expressed tumors in mice.

(4) Development of molecular imaging probes targeting hypoxic microenvironment in cancer
In various types of solid tumors, hypoxic microenvironment develops as abnormal proliferation outstrips the blood supply. Because this hypoxic region is involved in tumor malignancy, we developed molecular probes for hypoxic microenvironments.

・ For the hypoxia imaging probe, we selected acridine, which was reported to bind hypoxia-inducible factor-1α expressed in the hypoxic regions as a parent compound of the probe. An in vivo biodistribution study showed accumulation of a radioiodinated acridine probe in tumors expressing HIF-1α.
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