ORIGINAL RESEARCH n MOLECULAR IMAGING 818 radiology.rsna.org n Radiology: Volume 267: Number 3—June 2013 Molecular Imaging of Inflammation in Inflammatory Bowel Disease with a Clinically Translatable Dual-Selectin–targeted US Contrast Agent: Comparison with FDG PET/CT in a Mouse Model 1 Huaijun Wang, MD, PhD Steven Machtaler, PhD Thierry Bettinger, PhD Amelie M. Lutz, MD Richard Luong, BVSc, DACVP Philippe Bussat, MSc Sanjiv S. Gambhir, MD, PhD François Tranquart, MD, PhD Lu Tian, PhD Jürgen K. Willmann, MD Purpose: To develop and test a molecular imaging approach that uses ultrasonography (US) and a clinically translatable dual-targeted (P- and E-selectin) contrast agent (MB Selectin ) in the quantification of inflammation at the molecular level and to quantitatively correlate selectin-targeted US with fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and computed tomography (CT) in terms of visualization and quantification of different levels of inflammation in a murine acute colitis model. Materials and Methods: Animal studies were approved by the Institutional Admin- istrative Panel on Laboratory Animal Care at Stanford University. MB Selectin was developed by covalently binding an analog of the naturally occurring binding ligand P-se- lectin glycoprotein ligand 1 fused to a human fragment crystallizable(or Fc) domain onto the lipid shell of perfluo- robutane and nitrogen-containing MBs. Binding specificity of MB Selectin was assessed in vitro with a flow chamber as- say and in vivo with a chemically induced acute colitis mu- rine model. US signal was quantitatively correlated with FDG uptake at PET/CT and histologic grade. Statistical analysis was performed with the Student t test, analysis of variance, and Pearson correlation analysis. Results: MB Selectin showed strong attachment to both human and mouse P- and E-selectin compared with MB Control in vitro (P  .002). In vivo, US signal was significantly increased (P , .001) in mice with acute colitis (173.8 arbitrary units [au] 6 134.8 [standard deviation]) compared with control mice (5.0 au 6 4.5). US imaging signal strongly correlated with FDG uptake on PET/CT images (r = 0.89, P , .001). Ex vivo analysis enabled confirmation of inflammation in mice with acute colitis and high expression levels of P- and E-selectin in mucosal capillaries (P = .014). Conclusion: US with MB Selectin specifically enables detection and quan- tification of inflammation in a murine acute colitis model, leveraging the natural pathway of leukocyte recruitment in inflammatory tissue. US imaging with MB Selectin correlates well with FDG uptake at PET/CT imaging. q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl/doi:10.1148/radiol.13122509/-/DC1 1 From the Department of Radiology, Molecular Imaging Program at Stanford (H.W., S.M., A.M.L., S.S.G., J.K.W.), Department of Comparative Medicine (R.L.), and Depart- ment of Health, Research & Policy (L.T.), Stanford University School of Medicine, 300 Pasteur Dr, Room H1307; Stanford, CA 94305-5621; and Bracco Suisse, Geneva, Switzerland (T.B., P.B., F.T.). From the 2012 RSNA Annual Meeting. Re- ceived November 27, 2012; revision requested December 21; revision received January 2, 2013; accepted January 4; final version accepted January 7. H.W. supported by the Stanford Dean Fellowship award. J.K.W. supported in part by the Howard S. Stern Research Grant of the Society of Gastrointestinal Radiologists. Address correspondence to J.K.W. (e-mail: willmann@stanford.edu). q RSNA, 2013 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights.