Visualization 2: Integrated monolithic 3D MEMS scanner for switchable real time vertical/horizontal cross-sectional imaging

Visualization 2 Originally published in Optics Express on 08 February 2016 (oe-24-3-2145

Visualization 1: Integrated monolithic 3D MEMS scanner for switchable real time vertical/horizontal cross-sectional imaging

Visualization 1 Originally published in Optics Express on 08 February 2016 (oe-24-3-2145

Visualization 2: MEMS-based multiphoton endomicroscope for repetitive imaging of mouse colon

Dysplastic colon Originally published in Biomedical Optics Express on 01 August 2015 (boe-6-8-3074

Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2

We report the development, characterization, and validation of a peptide specific for the extracellular domain of HER2. This probe chemistry was developed for molecular imaging by using a structural model to select an optimal combination of amino acids that maximize the likelihood for unique hydrophobic and hydrophilic interactions with HER2 domain 3. The sequence KSPNPRF was identified and conjugated with either FITC or Cy5.5 via a GGGSK linker using Fmoc-mediated solid-phase synthesis to demonstrate flexibility for this chemical structure to be labeled with different fluorophores. A scrambled sequence was developed for control by altering the conformationally rigid spacer and moving both hydrophobic and hydrophilic amino acids on the C-terminus. We validated peptide specificity for HER2 in knockdown and competition experiments using human colorectal cancer cells in vitro, and measured a binding affinity of <i>k</i>_d = 21 nM and time constant of <i>k</i> = 0.14 min^–1 (7.14 min). We used this peptide with either topical or intravenous administration in a preclinical model of colorectal cancer to demonstrate specific uptake in spontaneous adenomas and to show feasibility for real time in vivo imaging with near-infrared fluorescence. We used this peptide in immunofluorescence studies of human proximal colon specimens to evaluate specificity for sessile serrated and sporadic adenomas. Improved visualization can be used endoscopically to guide tissue biopsy and detect premalignant lesions that would otherwise be missed. Our peptide design for specificity to HER2 is promising for clinical translation in molecular imaging methods for early cancer detection

Visualization 1: MEMS-based multiphoton endomicroscope for repetitive imaging of mouse colon

Normal colon Originally published in Biomedical Optics Express on 01 August 2015 (boe-6-8-3074

Multiplexed Targeting of Barrett’s Neoplasia with a Heterobivalent Ligand: Imaging Study on Mouse Xenograft in Vivo and Human Specimens ex Vivo

Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease that is rising rapidly in incidence and has poor prognosis. We developed a heterobivalent peptide to target detection of early Barrett’s neoplasia by combining monomer heptapeptides specific for either EGFR or ErbB2 in a heterodimer configuration. The structure of a triethylene glycol linker was optimized to maximize binding interactions to the surface receptors on cells. The Cy5.5-labeled heterodimer QRH*–KSP*–E3–Cy5.5 demonstrated specific binding to each target and showed 3-fold greater fluorescence intensity and 2-fold higher affinity compared with those of either monomer alone. Peak uptake in xenograft tumors was observed at 2 h postinjection with systemic clearance by ∼24 h in vivo. Furthermore, ligand binding was evaluated on human esophageal specimens ex vivo, and 88% sensitivity and 87% specificity were found for the detection of either high-grade dysplasia (HGD) or EAC. This peptide heterodimer shows promise for targeted detection of early Barrett’s neoplasia in clinical study