PURPOSE: To determine whether vascular-targeting effects can be detected in vivo using magnetic resonance imaging (MRI). METHODS AND MATERIALS: MR images of HCT-116 xenograft-bearing mice were acquired at 7 Tesla before and 24 hours after intraperitoneal injections of tirapazamine. Quantitative dynamic contrast-enhanced MRI analyses were performed to evaluate changes in tumor perfusion using two biomarkers: the volume transfer constant (K(trans)) and the initial area under the concentration-time curve (IAUC). We used novel implanted fiducial markers to obtain cryosections that corresponded to MR image planes from excised tumors; quantitative immunohistochemical mapping of tumor vasculature, perfusion, and necrosis enabled correlative analysis between these and MR images. RESULTS: Conventional histological analysis showed lower vascular perfusion or greater amounts of necrosis in the central regions of five of eight tirapazamine-treated tumors, with three treated tumors showing no vascular dysfunction response. MRI data reflected this result, and a striking decrease in both K(trans) and IAUC values was seen with the responsive tumors. Retrospective evaluation of pretreatment MRI parameters revealed that those tumors that did not respond to the vascular-targeting effects of tirapazamine had significantly higher pretreatment K(trans) and IAUC values. CONCLUSIONS: MRI-derived parameter maps showed good agreement with histological tumor mapping. MRI was found to be an effective tool for noninvasively monitoring and predicting tirapazamine-mediated central vascular dysfunction.
PURPOSE: To determine whether vascular-targeting effects can be detected in vivo using magnetic resonance imaging (MRI). METHODS AND MATERIALS: MR images of HCT-116 xenograft-bearing mice were acquired at 7 Tesla before and 24 hours after intraperitoneal injections of tirapazamine. Quantitative dynamic contrast-enhanced MRI analyses were performed to evaluate changes in tumor perfusion using two biomarkers: the volume transfer constant (K(trans)) and the initial area under the concentration-time curve (IAUC). We used novel implanted fiducial markers to obtain cryosections that corresponded to MR image planes from excised tumors; quantitative immunohistochemical mapping of tumor vasculature, perfusion, and necrosis enabled correlative analysis between these and MR images. RESULTS: Conventional histological analysis showed lower vascular perfusion or greater amounts of necrosis in the central regions of five of eight tirapazamine-treated tumors, with three treated tumors showing no vascular dysfunction response. MRI data reflected this result, and a striking decrease in both K(trans) and IAUC values was seen with the responsive tumors. Retrospective evaluation of pretreatment MRI parameters revealed that those tumors that did not respond to the vascular-targeting effects of tirapazamine had significantly higher pretreatment K(trans) and IAUC values. CONCLUSIONS: MRI-derived parameter maps showed good agreement with histological tumor mapping. MRI was found to be an effective tool for noninvasively monitoring and predicting tirapazamine-mediated central vascular dysfunction.
Authors: Yaacov Richard Lawrence; Bhadrasain Vikram; James J Dignam; Arnab Chakravarti; Mitchell Machtay; Boris Freidlin; Naoko Takebe; Walter J Curran; Soren M Bentzen; Paul Okunieff; C Norman Coleman; Adam P Dicker Journal: J Natl Cancer Inst Date: 2012-12-10 Impact factor: 13.506
Authors: Jennifer H E Baker; Alastair H Kyle; Kirsten L Bartels; Stephen P Methot; Erin J Flanagan; Andrew Balbirnie; Jordan D Cran; Andrew I Minchinton Journal: PLoS One Date: 2013-10-28 Impact factor: 3.240
Authors: Jennifer Hazel Elizabeth Baker; Alastair Hugh Kyle; Stefan Alexander Reinsberg; Firas Moosvi; Haley Margaret Patrick; Jordan Cran; Katayoun Saatchi; Urs Häfeli; Andrew Ivor Minchinton Journal: Clin Exp Metastasis Date: 2018-09-08 Impact factor: 5.150