In vivo measurement and imaging of tumor oxygenation using coembedded paramagnetic particulates

Magnetic Resonance in Medicine - Tập 52 Số 3 - Trang 650-657 - 2004
Govindasamy Ilangovan1, Anna Bratasz2, Haiquan Li2, Petra Schmalbrock3, Jay L. Zweíer2, Periannan Kuppusamy4
1Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Internal Medicine, Ohio State University, Columbus, USA.
2Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Internal Medicine, Ohio State University, Columbus, Ohio
3Department of Radiology, Ohio State University, Columbus, Ohio
4420 West 12th Ave., Room 114, Ohio State University, Columbus, OH 43210

Tóm tắt

AbstractTumor tissue oxygenation is an important parameter that is positively correlated to the chemo‐ or radiation treatment outcome of certain tumors. Hence, methods to accurately and noninvasively determine the concentration of oxygen (pO2) in tumors will be valuable. In this study, electron paramagnetic resonance (EPR) spectroscopy, utilizing microcrystalline particulates of lithium phthalocyanine (LiPc), was used to perform repeated measurements of pO2 as a function of tumor growth. We permanently embedded the particulates in the tumor by coimplanting them with RIF‐1 tumor cells during inoculation in mice. This procedure enabled repeated measurements of oxygen concentration in the tumor to be obtained for >2 weeks during its growth phase. The particulates were stable and nontoxic to the tumor cells. Both an in vitro clonogenic assay and an in vivo tumor growth rate examination in C3H mice showed no apparent effect on cell proliferation or tumor growth rate. The measurements indicated that the pO2 of the tumor decreased exponentially with tumor growth and reached hypoxic levels (∼4 mmHg) within 4 days after inoculation of the tumor cells. Spatial EPR imaging revealed a nonuniform distribution of the embedded particulates, which were localized mainly in the middle of the tumor volume. Oxygen mapping of the tumor, obtained by spectroscopic EPR imaging, showed significant variation of pO2 within the tumor. In summary, EPR spectroscopy and imaging with an embedded oximetry probe enabled accurate and repeated measurements of pO2 to be obtained in growing tumors under nonperturbing conditions. Magn Reson Med 52:650–657, 2004. © 2004 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1016/S0167-8140(00)00268-1

10.1016/S1053-4296(96)80032-4

Sun SY, 1999, Mediation of N‐(4‐hydoxyphenyl)retinamide‐induced apoptosis in human cancer cells by different mechanisms, Cancer Res, 59, 2493

10.1021/jm9608422

Krammer B, 2001, Vascular effects of photodynamic therapy, Anticancer Res, 21, 4271

10.1023/A:1015967305659

10.1002/mrm.10254

10.1002/jmri.10192

10.1016/S0360-3016(02)03035-3

10.2307/3578556

10.1016/0360-3016(90)90018-F

10.1093/jnci/84.9.707

10.1038/bjc.1987.213

10.1038/bjc.1995.426

10.1038/bjc.1995.427

10.1016/0003-2697(91)90339-U

Aboagye EO, 1997, Preclinical evaluation of the fluorinated 2‐nitroimidazole N‐(2‐hydroxy‐3,3,3‐trifluoropropyl)‐2‐(2‐nitro‐1‐imidazolyl) acetamide (SR‐4554) as a probe for the measurement of tumor hypoxia, Cancer Res, 57, 3314

10.1002/mrm.1910320112

10.1016/S0360-3016(98)00306-X

10.2307/3577798

10.1016/0360-3016(90)90307-6

10.1073/pnas.91.26.13047

10.1088/0031-9155/43/7/017

10.2307/3579262

10.1002/mrm.1910330214

Kuppusamy P, 1998, In vivo electron paramagnetic resonance imaging of tumor heterogeneity and oxygenation in a murine model, Cancer Res, 58, 1562

10.1073/pnas.90.12.5438

10.1006/jmrb.1994.1099

10.1002/mrm.1910310207

10.1002/mrm.1910400120

10.1021/jp010130

10.1002/ijc.2910420515

10.1002/(SICI)1097-0215(19960516)66:4<578::AID-IJC25>3.0.CO;2-2

10.1038/bjc.1982.41

10.1007/978-1-4684-4895-5_30

Sutherland RM, 1986, Oxygenation and differentiation in multicellular spheroids of human colon carcinoma, Cancer Res, 46, 5320

10.1016/S0360-3016(99)00157-1

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Magnetic Resonance in Medicine

Tập 52 Số 3

650-657

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