成果報告書詳細
管理番号20140000000504
タイトル*平成25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2015/3/25
報告書年度2013 - 2013
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, the majority of patients are in an advanced or metastatic condition at the time of diagnosis, resulting in poor prognosis. Earlier diagnosis and better treatments are needed urgently to improve the survival rate of patients with pancreatic cancer. We therefore developed molecular probes for the early detection of pancreatic cancer. This involved the design and synthesis of molecular probes targeting 1) the integrin αVβ6 which is involved in tumor progression of pancreatic ductal carcinoma, and 2) the GLP-1 receptor which is expressed in pancreatic endocrine tumors.

・For the integrin probe, radiogallium labeled peptide probes were designed and synthesized based on the structure of a radioiodinated probe which had enabled in vivo SPECT imaging of tumor expressing integrin αVβ6 last year. The biodistribution study with tumor bearing mice revealed that the radiogallium labeled probe accumulated in integrin αVβ6 positive tumor higher than integrin αVβ6 negative tumor.
・For the GLP-1 receptor probe, the development of automatic synthesis system of a 123I-labeled probe that showed high safety in an extended single-dose toxicity study last year was tested toward clinical trials. In addition, some promising candidate compounds were successfully synthesized using 68Ga as a radioisotope that can be obtained from a generator system.

(2) Development of molecular imaging probes targeting lung cancer.
A molecular-targeted approach has already been established for treatment of lung cancer. There is an increased expectation for personalized medicine for lung cancer based on prediction of its therapeutic effects. The aim of our research was to develop molecular imaging probes targeting EGFR or PI3K.

・Some probes were designed and synthesized based on the structures of EGFR inhibitors. Through the in vitro evaluations, a few promising candidate probes which showed high affinity with EGFR-TK were obtained.
・A probe candidate compound designed from the structure of PI3K inhibitor was evaluated in in vitro and in vivo experiments. This candidate probe showed high selectivity for PI3K in vitro, but this also showed rapid metabolism and degradation in in vivo biodistribution study.

(3) Development of molecular imaging probes targeting prostate cancer.
Treatment strategies for prostate cancer are determined based on risk assessment. We developed molecular probes for prostate cancer that involved designing a low molecular weight probe that targeted prostate-specific membrane antigen (PSMA). This probe was expected to have better biokinetics than existing probes.

・For the PSMA probe, a radiofluorinated probe was synthesized successfully based on the unsymmetrical urea probe ([123I]IGLCE) that we developed last year. An in vivo imaging study in mice achieved a clear PET image of tumors expressing PSMA. On the basis of results, we are now testing the toxicity of the novel radiofluorinated probe toward clinical trials.

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

・For the hypoxia-imaging probe, 18F-FMISO and 18F-FAZA were synthesized successfully for the comparison with 18F-labeled nitroimidazole probes that we synthesized last year. An in vivo imaging study in tumor bearing mice achieved clear PET images of hypoxic regions in the tumor.
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