ASSESSMENT OF HYPOXIA IN HUMAN CERVICAL CARCINOMA XENOGRAFTS BY DYNAMIC CONTRAST-ENHANCED MAGNETIC RESONANCE IMAGING

Purpose: Patients with advanced cervical cancer and highly hypoxic primary tumors show increased frequency of locoregional treatment failure and poor disease-free and overall survival rates. The potential usefulness of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing tumor hypoxia noninvasively was investigated in the present preclinical study. Methods and Materials: CK-160 and TS-415 human cervical carcinoma xenografts transplanted intramuscularly (i.m.) or subcutaneously (s.c.) in BALB/c nu/nu mice were subjected to DCE-MRI and measurement of fraction of radiobiologically hypoxic cells. Tumor images of K-trans (the volume transfer constant of Gd-DTPA) and v(e) (the extracellular volume fraction of the imaged tissue) were produced by pharmacokinetic analysis of the DCE-MRI data. Fraction of radiobiologically hypoxic cells was measured by using the paired survival curve method. Results: Fraction of radiobiologically hypoxic cells differed significantly among the four tumor groups. The mean values +/- SE were determined to be 44% +/- 7% (i.m. CK-160),77% +/- 10% (s.c. CK-160),23% +/- 5% (i.m. TS-415), and 52% +/- 6% (s.c. TS-415). The four tumor groups differed significantly also in K-trans, and there was an unambiguous inverse relationship between K-trans and fraction of radiobiologically hypoxic cells. On the other hand, significant differences among the groups in v(e) could not be detected. Conclusions: The study supports the clinical development of DCE-MRI as a method for assessing the extent of hypoxia in carcinoma of the cervix. (C) 2009 Elsevier Inc.