Xiaoyuan (Shawn) Chen

Research/Lab website:   Molecular Imaging Probe Laboratory (MIPL)

Molecular Imaging is a novel multidisciplinary field involving the efforts from molecular and cell biology to identify the molecular imaging target, radiochemistry and bioconjugation chemistry to develop suitable imaging probes, pharmacology to optimize the probes for optimal targeting efficacy and favorable in vivo kinetics, and image-capture techniques to non-invasively monitor the fate of molecular imaging probes in vivo. Aside from its basic diagnostic applications, molecular imaging also plays pivotal roles in treatment efficacy assessment, drug discovery, and understanding of molecular mechanisms in living systems. This lab is interested in developing and validating novel molecular imaging probes (monoclonal antibodies, minibodies, proteins, peptides and peptidomimetics) for visualization and quantification of molecular targets that are aberrantly expressed during tumor growth, angiogenesis and metastasis. The combination of anatomical (microMRI and microCT) and molecular imaging techniques (microPET, microSPECT, and NIR fluorescence imaging) will allow us to obtain molecular and functional information related to tumor growth and dissemination, and monitor specific molecular therapeutic efficacy.

Most solid tumors are angiogenesis dependent. Without neovascular blood supply, tumor cannot grow beyond 1-2 mm in diameter. The neovascularization of solid tumors is an essential feature of an aggressive tumor phenotype, although this issue remains somewhat controversial. Inhibition of angiogenesis has been shown to prevent tumor growth and even to cause tumor regression in various experimental models. Angiogenesis is a complex process involving extensive interplay between cells, soluble factors, and extracellular matrix (ECM) components. The construction of a vascular network requires different sequential steps including the release of proteases from “activated” endothelial cells with subsequent degradation of basement membrane surrounding the existing vessel, migration of endothelial cells into the interstitial space, endothelial cell proliferation, and differentiation into mature blood vessels. These processes are mediated by a wide range of angiogenic inducers, including growth factors, chemokines, angiogenic enzymes, endothelial specific receptors, and adhesion molecules. Each of these processes presents likely targets for possible diagnostic and therapeutic interventions. We are currently working closely with two important angiogenesis targets: integrin alpha(v)beta(3) and vascular endothelial growth factor receptor subtype-2 (VEGFR-2). Integrins expressed on endothelial cells modulate cell migration and survival during angiogenesis. Integrins expressed on carcinoma cells potentiate metastasis by facilitating invasion and movement across blood vessels. In several malignancies, tumor expression of integrin alpha(v)beta(3) correlates well with tumor progression. VEGF is a key regulator of tumor angiogenesis and is the most potent endothelial cell mitogen. Binding of VEGF to its receptor on the endothelial cell membrane stimulates the VEGF signaling pathway. VEGFR-2 (KDR/Flk-1) is the primary VEGF receptor on endothelial cells. Specific projects include multimodality (e.g. PET, SPECT, optical) imaging of tumor angiogenesis in vivo and tumor vessel specific delivery of gene, chemo, and radiotherapeutics.