Comparison of tumor blood perfusion assessed by dynamic contrast‐enhanced MRI with tumor blood supply assessed by invasive imaging

Abstract

Purpose: To evaluate the potential of Gd-DTPA-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for providing high-resolution tumor blood perfusion images. Materials and Methods:Xenografted tumors from two amelanotic human melanoma lines (A-07 and R-18) were used as preclinical models of human cancer. DCE-MRI was performed at a voxel size of 0.5 ϫ 0.2 ϫ 2.0 mm 3 with the use of spoiled gradient recalled sequences. We produced tumor images of E ⅐ F (where E is the initial extraction fraction, and F is perfusion) by subjecting the DCE-MRI data to Kety analysis, and then compared those images with images of tumor blood supply. We obtained high-resolution tumor blood supply images using the Bioscope silicon strip detector system to measure the uptake of Na 99m TcO 4 in histological preparations. We assessed the global blood supply by measuring the tumor uptake of three freely diffusible blood flow tracers: 86 RbCl, [ 14 C]IAP, and Na 99m TcO 4 .Results: E ⅐ F was found to mirror the blood supply well in A-07 and R-18 tumors. The mean E ⅐ F differed between the A-07 and R-18 tumors by a factor of ϳ1.6, and this difference was similar to the difference in the global blood supply. The intratumor heterogeneity in E ⅐ F was significant for tumors of both lines, and this heterogeneity was similar to the intratumor heterogeneity in the blood supply. The intratumor heterogeneity in the blood supply differed slightly between the A-07 and R-18 tumors, and even this difference was mirrored by the E ⅐ F images.Conclusion: E ⅐ F images of xenografted tumors reflect blood perfusion. This implies that E ⅐ F may be a useful parameter for improving cancer diagnostics and individualizing cancer treatment. This possibility deserves to be investigated thoroughly in clinical studies.

Coadministration of Vascular Disrupting Agents and Nanomedicines to Eradicate Tumors from Peripheral and Central Regions

“…[ 6,21 ] As such, drug-loaded nanoparticles are generally able to reach the cancer cells in the tumor periphery, but leave most tumor cells in the central regions unaffected due to the decreased vascularization of the central region compared to the periphery. [22][23][24] This, in turn, limits the efficacy of drug-loaded nanoparticles against solid tumor cancers. Therefore, in order to improve the therapeutic effi cacy of nanocarrier-based drugs, a strategy that can eradicate tumor cells in both the central and peripheral regions of a solid tumor is highly desired.…”

The relationship among tumor architecture, pharmacokinetics, pharmacodynamics, and efficacy of bortezomib in mouse xenograft models

“…However, meaningful correlation with response is difficult to achieve, as treatment with chemotherapy and angiogenic inhibitors can often themselves manipulate the expression of these proangiogenic factors. More recently, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been implemented as a noninvasive means to acquire images of tumor blood perfusion and predict response of tumors to therapeutic treatments (20)(21)(22)(23)(24). To complement the functional MRI readout, micro-computed tomographic (microCT) imaging of vascular casts can provide a high-resolution, threedimensional (3D) view of the tumor vessel architecture (25,26).…”

High-resolution 3D isotropic MR imaging of mouse flank tumours obtainedin vivowith solenoid RF micro-coil

“…MR angiography has been previously used to characterize intratumoural vasculature in mice (Fink et al 2003) and correlations made with histology (Graff et al 2005). Though, with a spatial resolution of 166 × 206 × 329 µm 3 , only larger vessels could be visualized.…”