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 Ktrans (the volume transfer constant of Gd-DTPA) and ve (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 Ktrans , and there was an unambiguous inverse relationship between Ktrans and fraction of radiobiologically hypoxic cells. On the other hand, significant differences among the groups in ve 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.