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In Vivo Evaluation of Combination Use of Two Radiosensitizers Iododeoxyuridine and Misonidazole: A Biodistribution Study with Whole-Body Autoradiography

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Author(s): Jeng-Jong Hwang | Hsin-Ell Wang | Hsin-Yu Fang | Fu-Du Chen | Frank Q. H. Ngo

Journal: Journal of Cancer Molecules
ISSN 1816-0735

Volume: 2;
Issue: 1;
Start page: 37;
Date: 2006;
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Keywords: biodistribution | whole-body autoradiography | radiosensitizer | [131I]IUdR | [18F]FMISO

ABSTRACT
AIM: To investigate the intratumoral localization and biodistribution of the combination administration of two radiosensitizers, iododeoxyuridine and misonidazole, in the mouse model to evaluate the availability and possible schedule for future clinical application.METHODS: Gamma-scintillation counting and whole-body autoradiography were adopted to investigate the biodistribution of [131I]iododeoxyuridine ([131I]IUdR) and [18F]misonidazole ([18F]FMISO) in KHT sarcoma-bearing C3H/HeN mice. RESULTS: The amounts of [131I]IUdR incorporated into the DNA of KHT sarcoma cells at 0.5, 2, 4, and 24-h postinjection with single dose were 3.76, 3.50, 3.41, and 3.29 μBq/cell, respectively. The tumor/brain ratios of [131I]IUdR calculated from the % injected dose per gram tissue were 14.5, 13.0, 11.5, and 88.0, respectively, at 0.5, 2, 4, and 24 h after [131I]IUdR injection; the tumor/blood ratios were 0.76, 0.76, 0.70, and 12.57; while the tumor/muscle ratios were 3.22, 3.71, 2.56, and 22.00, respectively. On the other hand, the tumor/brain ratios of [18F]FMISO were 1.29, 1.21, 1.26, and 2.48 at 0.5, 1, 2, and 4 h after [18F]FMISO injection, respectively; while the tumor/muscle ratios were 1.41, 1.30, 1.25, and 2.21. The tumor/muscle ratios were 4.0, 2.0, and 4.7 for [131I]IUdR alone, [131I]IUdR and [18F]FMISO simultaneously for 4 h, and [131I]IUdR 2 h followed by [18F]FMISO for another 2 h, respectively. The whole-body autoradiography showed uptake of [131I]IUdR at the peripheral region of tumor while [18F]FMISO at the deeper sites. CONCLUSION: [131I]IUdR was accumulated at the superficial area while [18F]FMISO at the deeper hypoxic site of tumor. Combination use of both radiosensitizers, [131I]IUdR first 2 h followed by [18F]FMISO for another 2 h, may be optimal to enhance the radiosensitization during radiotherapy.
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