Combined Macromolecular DCE-MRI and Hyperpolarized 13C MRSI Indicate an Association Between Vascular and Metabolic Effects of Imatinib in a Prostate Cancer Bone Metastasis Model

Hagit Dafni¹, Peder E. Z. Larson¹, Simon Hu¹, Robert Bok¹, Chris Ward¹, Chunsheng Wang¹, Lynn DeLosSantos¹, Xiaoliang Zhang¹, Daniel B. Vigneron¹, Sabrina M. Ronen¹

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.