Ultrasound molecular imaging of secreted frizzled related protein-2 expression in murine angiosarcoma.
Angiosarcoma is a biologically aggressive vascular malignancy with a high metastatic potential. In the era of targeted medicine, knowledge of specific molecular tumor characteristics has become more important. Molecular imaging using targeted ultrasound contrast agents can monitor tumor progression non-invasively. Secreted frizzled related protein 2 (SFRP2) is a tumor endothelial marker expressed in angiosarcoma. We hypothesize that SFRP2-directed imaging could be a novel approach to imaging the tumor vasculature. To develop an SFRP2 contrast agent, SFRP2 polyclonal antibody was biotinylated and incubated with streptavidin-coated microbubbles. SVR angiosarcoma cells were injected into nude mice, and when tumors were established the mice were injected intravenously with the SFRP2 -targeted contrast agent, or a control streptavidin-coated contrast agent. SFRP2 -targeted contrast agent detected tumor vasculature with significantly more signal intensity than control contrast agent: the normalized fold-change was 1.6 ± 0.27 (n = 13, p = 0.0032). The kidney was largely devoid of echogenicity with no significant difference between the control contrast agent and the SFRP2-targeted contrast agent demonstrating that the SFRP2-targeted contrast agent was specific to tumor vessels. Plotting average pixel intensity obtained from SFRP2-targeted contrast agent against tumor volume showed that the average pixel intensity increased as tumor volume increased. In conclusion, molecularly-targeted imaging of SFRP2 visualizes angiosarcoma vessels, but not normal vessels, and intensity increases with tumor size. Molecular imaging of SFRP2 expression may provide a rapid, non-invasive method to monitor tumor regression during therapy for angiosarcoma and other SFRP2 expressing cancers, and contribute to our understanding of the biology of SFRP2 during tumor development and progression.
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America ; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America ; North Carolina State University, Raleigh, North Carolina, United States of America.
James K
JK
Tsuruta
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America ; UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Nancy
N
Klauber-DeMore
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America ; North Carolina State University, Raleigh, North Carolina, United States of America.
Jason
J
Streeter
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Jennifer
J
Samples
UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Cam
C
Patterson
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America ; North Carolina State University, Raleigh, North Carolina, United States of America ; Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina, United States of America.
Russell J
RJ
Mumper
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
David
D
Ketelsen
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America ; North Carolina State University, Raleigh, North Carolina, United States of America ; Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina, United States of America.
Paul
P
Dayton
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics*; D019921:Biotinylation; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D015870:Gene Expression; D006394:Hemangiosarcoma / Q000098:blood supply* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D057054:Molecular Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000473:pathology; D019809:Streptavidin / Q000737:chemistry; D014463:Ultrasonography; D000094742:Secreted Frizzled-Related Proteins
D000906:Antibodies; D014408:Biomarkers, Tumor; D003287:Contrast Media; D008565:Membrane Proteins; D019809:Streptavidin; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins