2003 Fiscal Year Final Research Report Summary
Suppression of metastatic lesions of cancer with cooperative effects of internal radiotherapy and antiangiogenic therapy
| Project/Area Number |
14570843
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kanazawa University |
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Principal Investigator |
KINUYA Seigo Kanazawa University, Graduate School of Medical Sciences, Assistant, 医学系研究科, 助手 (20281024)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Radioimmunotherapy / Internal radiotherapy / antiangiogenic therapy / Colon cancer / Metastasis / I-131 / Re-186 / Pretherapeutic prediction |
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| Research Abstract |
1.Benefits of Combination therapy of radioimmunotherapy(RIT)using ^<131>I-labeled anti-colorectal carcinoma monoclonal antibody, A7, and antiangiogenic therapy employing thalidomide or 2-methoxyestradiol were demonstrated in a subcutaneous xenograft model and a liver metastasis model of human colon cancer cells.Preceeding antiangiogenic therapy did not affect specific targeting of ^<131>I-A7 in metastatic lesions. Accumulation of ^<131>I-A7 was higher in smaller metastatic lesions, indicating the feasibility of RIT in adjuvant clinical settings.gurthermore, the Combination of antiangiogenic therapy did not affect the seventy of myelotoxicity Caused by RIT.These results suggest that' the combined utility of antianglogenic therapy and RIT may synergistically effect treatment of cancer lesions ; that is, antiangiogenic therapy induces dormancy of lesions and RAT may eradicate this population of dormant cells.
2.To further Verify the role of RAT with β-emitters, efficacy of RAT with ^<186>Re-A7 was compared to that with ^<131>I-A7 in a liver metastasis model and a pentoneal dissemination model of colon cancer cells. ^<186>Re emits β-particles of energy higher than ^<131>I.At maximum tolerated doses, ^<186>Re-RIT produced better therapeutic results in both models.Therefore, the efficacy of the regimen combined with antiangiogenic therapy would be further improved by the usage of ^<186>Re.
3.Pretherapeutic prediction of therapeutic outcomes is extremely important for the good management of cancer patients. Many reports have demonstrated the feasibility of scintigraphic assessment Using radiopharmaceuticals such as ^<99m>Tc-sestamibi in this regard.The present investigation revealed that hypoxic conditions of tumor tissues reduced the tracer accumulation, acdnceming the mechanism of scintigraphic findings in this issue.
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