Dynamic contrast-enhanced perfusion parameters in ovarian cancer: Good accuracy in identifying high HIF-1[alpha] expression

Hypoxia significantly influences treatment response and clinical outcome in solid tumors. A noninvasive marker for hypoxia will help physicians in treatment planning and encourage the efficient use of hypoxia targeted therapies. The purpose of this study was to investigate whether pharmacokinetic dynamic contrast-enhanced (DCE) perfusion parameters are associated with a specific marker of hypoxia, hypoxia-inducible factor 1 alpha (HIF-1[alpha]) in ovarian cancer (OC). Thirty-eight patients with primary OC were enrolled in this prospective study approved by the local ethical committee. Patients underwent dynamic gadolinium-enhanced 3.0 T MRI as part of their staging investigations. Pharmacokinetic perfusion parameters, including a rate constant for transfer of contrast agent from plasma to extravascular extracellular space (EES) (K.sup.trans) and a rate constant from EES to plasma (K.sub.ep ), were measured by drawing two types of regions of interest (ROIs): a large solid lesion (L-ROI) and a solid, most enhancing small area (S-ROI) (NordicICE platform). Tissue samples for immunohistochemical analysis were collected during surgery. Kruskal-Wallis, Mann-Whitney U and Chi-square tests were used in statistical analyses. Receiver Operating Characteristic curve analyzes were done for DCE parameters to discriminate high HIF-1[alpha] expression. Pharmacokinetic perfusion parameters K.sup.trans and K.sub.ep were inversely associated with HIF-1[alpha] expression (K.sup.trans L-ROI P = 0.021; K.sup.trans S-ROI P = 0.018 and K.sub.ep L-ROI P = 0.032; K.sub.ep S-ROI P = 0.033). K.sup.trans and K.sub.ep showed good accuracy in identifying high HIF-1[alpha] expression (AUC = 0.832 K.sup.trans L-ROI; 0.840 K.sup.trans S-ROI; 0.808 K.sub.ep L-ROI and 0.808 K.sub.ep L-ROI). This preliminary study demonstrated that pharmacokinetic DCE-MRI perfusion parameters are associated with the hypoxia specific marker, HIF-1[alpha] in OC. DCE-MRI may be a useful supplementary tool in the characterization of OC tumors in a staging investigation.