title: Vasculature-specific MRI reveals differential anti-angiogenic effects of a biomimetic peptide in an orthotopic breast cancer model.
abstract: Translational vasculature-specific MRI biomarkers were used to measure the effects of a novel anti-angiogenic biomimetic peptide in an orthotopic MDA-MB-231 human triple-negative breast cancer model at an early growth stage. In vivo diffusion-weighted and steady-state susceptibility contrast (SSC) MRI was performed pre-treatment and 2 weeks post-treatment in tumor volume-matched treatment and control groups (n = 5/group). Treatment response was measured by changes in tumor volume; baseline transverse relaxation time (T2); apparent diffusion coefficient (ADC); and SSC-MRI metrics of blood volume, vessel size, and vessel density. These vasculature-specific SSC-MRI biomarkers were compared to the more conventional, non-vascular biomarkers (tumor growth, ADC, and T2) in terms of their sensitivity to anti-angiogenic treatment response. After 2 weeks of peptide treatment, tumor growth inhibition was evident but not yet significant, and the changes in ADC or T2 were not significantly different between treated and control groups. In contrast, the vascular MRI biomarkers revealed a significant anti-angiogenic response to the peptide after 2 weeks—blood volume and vessel size decreased, and vessel density increased in treated tumors; the opposite was seen in control tumors. The MRI results were validated with histology—H&E staining showed no difference in tumor viability between groups, while peptide-treated tumors exhibited decreased vascularity. These results indicate that translational SSC-MRI biomarkers are able to detect the differential effects of anti-angiogenic therapy on the tumor vasculature before significant tumor growth inhibition or changes in tumor viability.
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.forename: Esak
authors.initials: E
authors.lastname: Lee
authors.forename: Charlesa
authors.initials: C
authors.lastname: Plummer
authors.forename: Stacy
authors.initials: S
authors.lastname: Gil
authors.forename: Aleksander S
authors.initials: AS
authors.lastname: Popel
authors.forename: Arvind P
authors.initials: AP
authors.lastname: Pathak
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D032701:Biomimetics; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D010455:Peptides