Hagit Dafni1, Peder E. Z. Larson1, Simon Hu1, Robert Bok1, Chris Ward1, Chunsheng Wang1, Lynn DeLosSantos1, Xiaoliang Zhang1, Daniel B. Vigneron1, Sabrina M. Ronen1
1Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
Combined vascular and metabolic changes were detected in responses to 2-days imatinib (PDGFR inhibitor) and paclitaxel treatment of a bone metastases model (PC-3MM2). Macromolecular DCE-MRI, using albumin-GdDTPA, indicated decrease in vascular permeability and 13C-MRSI, using hyperpolarized pyruvate, indicated reduced lactate signal. Immunohistochemistry suggested HIF-1 as a connecting link, as HIF-1 is regulated by receptor tyrosine kinases (i.e. PDGFR) signaling and controls both LDH (catalyzes pyruvate to lactate conversion) and VEGF (involved in the vascular response to imatinib, as we showed previously). Thus, combining DCE-MRI, hyperpolarized 13C-MRSI and immunohistochemistry can help reveal the mechanism and identify biomarkers of response to treatment.