Optical Contrast Agents and Imaging Systems for Detection and Diagnosis of Cancer

Department of Bioengineering, Rice University, Houston, TX, USA.
International Journal of Cancer (Impact Factor: 5.09). 11/2008; 123(9):1979-90. DOI: 10.1002/ijc.23858
Source: PubMed


Molecular imaging has rapidly emerged as a discipline with the potential to impact fundamental biomedical research and clinical practice. Within this field, optical imaging offers several unique capabilities, based on the ability of cells and tissues to effect quantifiable changes in the properties of visible and near-infrared light. Beyond endogenous optical properties, the development of molecularly targeted contrast agents enables disease-specific morphologic and biochemical processes to be labeled with unique optical signatures. Optical imaging systems can then provide real-time visualization of pathophysiology at spatial scales from the subcellular to whole organ levels. In this article, we review fundamental techniques and recent developments in optical molecular imaging, emphasizing laboratory and clinical systems that aim to visualize the microscopic and macroscopic hallmarks of cancer.

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Available from: Rebecca Kortum, Aug 06, 2014
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    • "Most conventional approaches for utilizing NIRF dyes in cancer imaging require chemical conjugation of NIR fluorophores with appropriate tumor-specific ligands, including metabolic substrates, aptamers, growth factors, and antibodies [5e7]. A number of surface molecules have been tested as targets, including membrane receptors, extracellular matrices, cancer cell surface-specific markers, and neovascular endothelial cell-specific markers [8] [9]. "
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    ABSTRACT: Near-infrared fluorescence (NIRF) imaging agents are promising tools for noninvasive cancer imaging. Here, we explored the mechanistic properties of a specific group of NIR heptamethine carbocyanines including MHI-148 dye we identified and synthesized, and demonstrated these dyes to achieve cancer-specific imaging and targeting via a hypoxia-mediated mechanism. We found that cancer cells and tumor xenografts exhibited hypoxia-dependent MHI-148 dye uptake in vitro and in vivo, which was directly mediated by hypoxia-inducible factor 1α (HIF1α). Microarray analysis and dye uptake assay further revealed a group of hypoxia-inducible organic anion-transporting polypeptides (OATPs) responsible for dye uptake, and the correlation between OATPs and HIF1α was manifested in progressive clinical cancer specimens. Finally, we demonstrated increased uptake of MHI-148 dye in situ in perfused clinical tumor samples with activated HIF1α/OATPs signaling. Our results establish these NIRF dyes as potential tumor hypoxia-dependent cancer-targeting agents and provide a mechanistic rationale for continued development of NIRF imaging agents for improved cancer detection, prognosis and therapy.
    Biomaterials 06/2014; 35(28). DOI:10.1016/j.biomaterials.2014.05.073 · 8.56 Impact Factor
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    • "Over the past several years, there has been an explosion of reports describing successful in vivo NIR fluorescence imaging [11-18]. Several optical contrast agents have been developed for the detection of various types of cancer [19-21]. Although most of these studies are qualitative, quantitative studies are beginning to emerge. "
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    ABSTRACT: The aim of this study was to develop the near infrared fluorescence (NIRF)-based imaging agent for the visualization of vascular endothelial growth factor (VEGF) in colon cancer. AlexaFluor 750 conjugating with bevacizumab, and injected intravenously into nude mice bearing VEGF over-expressing HT29 human colorectal cancer. Optical imaging was performed at 15 min, 24 h and 48 h post injection. Immunofluorescences staining of the tumor sections were performed. HT29 colorectal cancer xenografts were clearly visualized with bevacizumab-AlexaFluor 750. Ex vivo analysis showed 2.1 +/- 0.4%, 37.6 +/- 6.3% and 38.5 +/- 6.2% injected dose/g accumulated in the tumors at 15 min, 24 h and 48 h respectively. Tumor uptake was significantly decreased in pretreated with excess of bevacizumab (p = 0.002). Immunofluorescence analysis showed strong staining of anti-CD 31 antibody around the blood vessels. Anti-VEGF-A and bevacizumab showed heterogeneous expression throughout the tumor. Current study successfully detected the VEGF expression in HT29 colorectal cancer xenografts, signifying as a potential agent for non-invasive imaging of VEGF expression, which may be applied in clinical practice.
    Journal of Biomedical Science 04/2014; 21(1):35. DOI:10.1186/1423-0127-21-35 · 2.76 Impact Factor
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    • "Combined with the advances in imaging systems [16]–[20], reconstruction algorithms [21]–[27] and optical contrast agents [28], [29], more applications are expected in fundamental researches , drug development, and clinical experiments. Nevertheless, challenges remain in the 4-D FDOT reconstruction . "
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    ABSTRACT: Dynamic fluorescence diffuse optical tomography (FDOT) is important for the research of drug delivery, medical diagnosis and treatment. Conventionally, dynamic tomographic images are reconstructed frame by frame, independently. This approach fails to account for the temporal correlations in measurement data. Ideally, the entire image sequence should be considered as a whole and a four-dimensional (4-D) reconstruction should be performed. However, the fully 4-D reconstruction is computationally intensive. In this paper, we propose a new 4-D reconstruction approach for dynamic FDOT, which is achieved by applying a temporal Karhunen-Loève (KL) transformation to the imaging equation. By taking advantage of the decorrelation and compression properties of the KL transformation, the complex 4-D optical reconstruction problem is greatly simplified. To evaluate the performance of the method, simulation, phantom, and in vivo experiments (N=7) are performed on a hybrid FDOT/x-ray computed tomography imaging system. The experimental results indicate that the reconstruction images obtained by the KL method provide good reconstruction quality. Additionally, by discarding high-order KL components, the computation time involved with fully 4-D reconstruction can be greatly reduced in contrast to the conventional frame-by-frame reconstruction.
    08/2012; 31(11). DOI:10.1109/TMI.2012.2213828
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