期刊
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
卷 84, 期 3, 页码 E393-E399出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ijrobp.2012.05.005
关键词
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资金
- National Institutes of Health [R01 CA84596, R24 CA83084, P01 CA115675, P50 CA86438]
- Geoffrey Beene Cancer Research Foundation
Purpose: The behavior of copper-64-diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-64-ATSM) in hypoxic tumors was examined through a combination of in vivo dynamic positron emission tomography (PET) and ex vivo autoradiographic and histologic evaluation using a xenograft model of head-and-neck squamous cell carcinoma. Methods and Materials: Cu-64-ATSM was administered during dynamic PET imaging, and temporal changes in Cu-64-ATSM distribution within tumors were evaluated for at least 1 hour and up to 18 hours. Animals were sacrificed at either 1 hour (cohort A) or after 18 hours (cohort B) postinjection of radiotracer and autoradiography performed. Ex vivo analysis of microenvironment subregions was conducted by immunohistochemical staining for markers of hypoxia (pimonidazole hydrochloride) and blood flow (Hoechst-33342). Results: Kinetic analysis revealed rapid uptake of radiotracer by tumors. The net influx (K-i) constant was 12-fold that of muscle, whereas the distribution volume (V-d) was 5-fold. PET images showed large tumor-to-muscle ratios, which continually increased over the entire 18-hour course of imaging. However, no spatial changes in Cu-64-ATSM distribution occurred in PET imaging at 20 minutes postinjection. Microscopic intratumoral distribution of Cu-64-ATSM and pimonidazole were not correlated at 1 hour or after 18 hours postinjection, nor was Cu-64-ATSM and Hoechst-33342. Conclusions: The oxygen partial pressures at which Cu-64-ATSM and pimonidazole are reduced and bound in cells are theorized to be distinct and separable. However, this study demonstrated that microscopic distributions of these tracers within tumors are independent. Researchers have shown Cu-64-ATSM uptake to be specific to malignant expression, and this work has also demonstrated clear tumor targeting by the radiotracer. (C) 2012 Elsevier Inc.
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