RESEARCH INTEREST
Development of Targeted Molecular Imaging Agents
Dr. Sutcliffe’s research involves the design, synthesis and in vivo evaluation of targeted molecular imaging agents with a focus on PET. Her group has developed rapid radiolabeling technologies using both solid-phase and solution-phase chemistries to incorporate the short half-life PET radionuclide 18F into peptides. Peptide based radiopharmaceuticals are gaining extensive attention as targeted molecular imaging agents. It is therefore important that technologies are developed that allow these agents to be synthesized rapidly and screened both in vitro and in vivo to assess their efficacy. Her group applies radiolabeled peptides to target cell surface receptors in vivo using small animal imaging. Major cell surface receptors of interest include the integrin receptors alpha(v)beta(3) and alpha(v)beta(6). Integrins are cell surface glycoproteins involved in cell-cell and cell- extracellular matrix interactions. Their over expression has been associated with many diseases including cancer. In particular alpha(v)beta(6) is expressed at low or undetectable levels on normal tissue and is upregulated on many cancers including oral squamous cell carcinoma, breast cancer, pancreatic cancer and has recently been identified as a marker of prognosis in colon and lung cancer. In vivo imaging of this receptor could therefore have a significant impact on patient diagnosis, care and management. Dr Sutcliffe’s group uses two approaches to develop targeted molecular imaging agents to image cell surface receptors A “rational approach” based on known binding structures and a “random approach” using the one-bead-one-compound molecular library methodology. Peptides are synthesized using standard Fmoc chemistries, screened in vitro for affinity and selectivity and subsequently radiolabeled and screened in vivo using small animal imaging.
RESEARCH FACILITY
Sutcliffe Lab Website
PUBLICATIONS
Jan Marik and Julie L. Sutcliffe, Click for PET: Rapid preparation of [18F]fluoropeptides using Cu(I) catalyzed 1,3-dipolar cycloaddition. Tetrahedron Letters, 2006, Vol 47, Issue 37.
Jan Marik, Sven H. Hausner, Lauren A. Fix, M. Karen Gagnon, Julie L. Sutcliffe, Solid phase synthesis of 2- [18F]fluoropropionyl peptides. Bioconjugate Chemistry, 17, 1017-1021 (2006).
Jan Marik, and Julie L. Sutcliffe, Fully automated preparation of n.c.a. 4-[18F]fluorobenzoic acid and N-succinimidyl 4-[18F]fluorobenzoate using Siemens CTI/CPCU chemistry module. Appl Radiat Isot. 2007 Feb;65(2):199-203.
DiCara D, Rapisarda C, Sutcliffe JL, Violette SM, Weinreb PH, Hart IR, Howard MJ, Marshall JF. Structure-function analysis of Arg-Gly-Asp helix motifs in alpha v beta 6 integrin ligands. J Biol Chem. 2007 Mar 30;282(13):9657-65. Epub 2007 Jan 23.
Hausner, S. H.; DiCara, D.; Marik, J.; Marshall, J. F.; Sutcliffe, J. L.; Use of a peptide derived from foot-and-mouth-disease-virus (FMDV) for the non-invasive imaging of human cancer: Generation and evaluation of [18F]FBA-A20FMDV2 for in vivo imaging of integrin alpha(v)beta(6) expression with Positron Emission Tomography; Cancer Res. 2007 Aug 15;67(16):7833-40.
MAJOR RESEARCH INTERESTS
Development of novel imaging probes and chemistries for PET.
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