2002 Fiscal Year Final Research Report Summary
Radio immunotherapy of malignant tumors by pretargeting
| Project/Area Number |
11670911
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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 | Saitama Medical School |
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Principal Investigator |
HOSONO Makoto Saitama Medical School, Faculty of Medicine, assistant professor, 医学部, 講師 (00281303)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Takeo Saitama Medical School, Faculty of Medicine, assistant professor, 医学部, 講師 (70241883)
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| Project Period (FY) |
1999 – 2002
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| Keywords | small cell lung carcinoma / antineural cell adhesion molecule / bispecific antibody / pretargeting |
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| Research Abstract |
The "affinity enhancement system", a two-step targeting technique using bispecific antibody and radiolabeled bivalent hapten, has been reported to be useful for the targeting of carcinoembryonic antigen-expressing tumors. The purpose of this study was to evaluate the efficacy of this method for targeting human small cell lung cancer using an antineural cell adhesion molecule antibody.
Antineural cell adhesion molecule/antihistamine bispecific anti-body NKI NBLIJ79 was prepared by coupling an equimolecular quantity of a Fab' fragment of NK1NBL1 to a Fab fragment of antihistamine 679. Athymic mice inoculated with NC1-H69 small cell lung cancer cells expressing neural cell adhesion molecule were administered bispecific antibody and then 48 h later 1251-labeled bivalent histamine hapten. 1251-labeled in tact NKINBLI was injected into other groups of mice. Biodisributions were examined as a function of time.
In mice of the two-step targeting, tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 1.4 ± 1.1, 10.8 ± 13.2 and 4.6 ± 4.7, respectively, at 5 h, whereas 1251-labeled NK1NBL1 showed tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 0.3 ± 0.1, 1.1 ± 0.2 and 0.9 ± 0.1, respectively, at 5 h. Dosimetry showed that tumor-to-liver and -to-bone marrow ratios of absorbed irradiation doses were 14.3 and 16.8 for the two-step method and 4.2 and 2.6 for the one-step method. This suggested that the affinity enhancement system could enhance the therapeutic potential of the antineural cell adhesion molecule antibody NK1NBL1.
This two-step targeting method seems promising for the diagnosis and therapy of small cell lung cancer by giving enhanced tumor-to-normal tissue contrast.
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