Abstract
BackgroundHigh interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI.MethodsCK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm3 and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model.ResultsWhen gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent.ConclusionGadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.
Highlights
High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma
Tumor models CK-160 human cervical carcinoma xenografts growing in adult female BALB/c nu/nu mice were used as tumor models [16]
The Tofts model gave good curve fits to the plots of Ct versus T, but the uncertainty in the calculations of VTbofts were too large that reliable values for this parameter could be obtained, probably because the temporal resolution of the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was not sufficiently high
Summary
High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A large prospective study of the association between tumor IFP and outcome of treatment has been carried out in patients with locally advanced cervical carcinoma at Princess Margaret Hospital in Toronto [8,9]. The main findings reported by the Toronto group have been confirmed in a smaller prospective study of cervical carcinoma patients treated with radiation therapy at Chungnam National University Hospital in Daejeon [10]. Taken together, these studies suggest that cervical carcinoma patients with highly elevated tumor IFP may benefit from aggressive treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
