Preclinical evaluation and validation of ~(18)FHX4,a promising hypoxia marker for imaging

Dubois L.J.; Lieuwes N.G.; Janssen M.H.M.Peeters W.J.M.Windhorst A.D.Walsh J.C.Kolb H.C.?llers M.C.Bussink J.Van Dongen G.A.M.S.Van Der Kogel A.Lambin P.

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Preclinical evaluation and validation of ~(18)FHX4,a promising hypoxia marker for imaging

机译：Preclinical evaluation and validation of ~(18)FHX4,a promising hypoxia marker for imaging

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Hypoxia has been shown to be an important microenvironmental parameter influencing tumor progression and treatment efficacy. Patient guidance for hypoxia-targeted therapy requires evaluation of tumor oxygenation, preferably in a noninvasive manner. The aim of this study was to evaluate and validate the uptake of ~(18)F HX4, a novel developed hypoxia marker for PET imaging. A heterogeneous accumulation of ~(18)FHX4 was found within rat rhabdomyosarcoma tumors that was significantly (P < 0.0001) higher compared with the surrounding tissues, with temporal increasing tumor-to-blood ratios reaching a plateau of 7.638 ± 0.926 and optimal imaging properties 4 h after injection. ~(18)FHX4 retention in normal tissues was found to be short-lived, homogeneous and characterized by a fast progressive temporal clearance. Heterogeneity in ~(18)FHX4 tumor uptake was analyzed based on 16 regions within the tumor according to the different orthogonal planes at the largest diameter. Validation of heterogeneous 18FHX4 tumor uptake was shown by a strong and significant relationship (r = 0.722; P < 0.0001) with the hypoxic fraction as calculated by the percentage pimonidazole-positive pixels. Furthermore, a causal relationship with tumor oxygenation was established, because combination treatment of nicotinamide and carbogen resulted in a 40 reduction (P < 0.001) in ~(18)FHX4 tumor accumulation whereas treatment with 7 oxygen breathing resulted in a 30 increased uptake (P < 0.05). ~(18)FHX4 is therefore a promising candidate for noninvasive detection and evaluation of tumor hypoxia at a macroscopic level.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2011年第35期|14620-14625|共6页
作者
Dubois L.J.; Lieuwes N.G.; Janssen M.H.M.Peeters W.J.M.Windhorst A.D.Walsh J.C.Kolb H.C.?llers M.C.Bussink J.Van Dongen G.A.M.S.Van Der Kogel A.Lambin P.;
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作者单位

Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands;

Departments of Nuclear Medicine and PET Research, VU University Medical Centre, 1081 HV Amsterdam, Netherlands;

Siemens Molecular Imaging Medical Solutions, Culver City, CA 90231, United StatesDepartment of Radiation Oncology (MaastRO Lab.), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, 6200 MD Maastricht, Netherlands;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Cancer; Experimental research; Nuclear medicine;

Preclinical evaluation and validation of ~(18)FHX4,a promising hypoxia marker for imaging

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