2001 Fiscal Year Final Research Report Summary
Amplification of Targeting of Radiolabel led Antibody by Overcoming Tumor Hypoxia
| Project/Area Number |
10670838
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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 |
YOKOYAMA Kunihiko Kanazawa University, Hospital, Lecturer, 医学部・附属病院, 講師 (60230661)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBA Kazuhiro Kanazawa University Radioisotope Center, Associate Professor, アイソトープ総合センター, 助教授 (40143929)
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| Project Period (FY) |
1998 – 2000
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| Keywords | radioimmunotherapy / radiosensitivity / tumor hypoxia / hypoxia avid tracer / hypoxia imaging / neoangiogenesis |
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| Research Abstract |
Objectives: Hypoxia is known to increase resistance to radiation therapy. Moreover, hypoxia induced after certain anticancer drugs initiates neoangiogenesis in tumor tissues resulting in the first step of distant metastases. Therefore, it is clinically important to assess tumor hypoxia as an indicator of radio- and chemotherapeutic effect as well as a prognosis factor. In hypoxic tissues, 4,9-diaza-3, 3, 10, 10-tetramethyl dodecan-2, 11-dione bisoxime (HL91) is designed to accumulate and retained. In this study, we have attempted to evaluate Tc-99m-HL91 as a tumor targeting agent comparing with Tl-201, a flow dependent tumor-seeking agent.
Methods: P388 mouse leukemia, Lewis lung cancer (LLC) and B-16 melanoma cells were used either for in vitro cell binding assay (CBA) or pharmakokinetic studies in tumor xenografted mouse models. CBA was performed under hypoxic condition and compared to normoxic incubation. The biodistribution was assessed at 15, 60, 120 and 180 min after administratio
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n of Tc-99m-HL91 and Tl-201. Imaging studies were also performed with both tracers.
Results: Under normoxic condition %binding to P388 of Tc-99m-HL91 was low throughout the study (2.4 ± 0.11 % at 20 min and 3.7 ± 0.14% at 240 min), whereas under hypoxic condition %binding was increased with time (2.8 ± 0.11 % at 20 min and 40.4 ± 0.91% at 240 min). The biodistribution study showed comparable tumor uptake to B-16 between both tracers (HL91: 3.1% at 15 min, 2.7% at 180 min vs. Tl-201: 2.5%, 3.2%, respectively). However, the background activity of Tc-99m HL91 is lower than Tl-201 (muscle: HL91: 3.2% at 15 min, 0.8% at 180 min vs. Tl-201: 4.9%, 7.0%, respectively). The transplanted LLC and B-16 tumors were clearly visible with Tc-99m-HL91 and distribution pattern in the tumor was discordant with Tl-201.
Conclusion: Tc-99m-HL91 preferentially accumulates into hypoxic cells and is not flow dependent. Therefore, Tc-99m-HL91 can be used to detect tumor localization and provide the information on status of tumor hypoxia, which is distinctively different from Tl-201. Less
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