Automated analysis of investigational near-infrared fluorescence lymphatic imaging in humans.
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ABSTRACT:
SUBMITTER: Zhang J
PROVIDER: S-EPMC3395493 | biostudies-other | 2012 Jul
REPOSITORIES: biostudies-other
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Project description:The relationship between lymphatic and venous malformations in Klippel-Trénaunay syndrome is difficult to assess. Herein the authors describe near-infrared fluorescence lymphatic imaging to assess the lymphatics of a subject with a large port-wine stain and right leg edema. Although lymphatic vessels in the medial, affected knee appeared dilated and perhaps tortuous, no definitive abnormal lymphatic pooling or propulsion was observed. The lymphatics in the affected limb were well defined but less numerous than in the contralateral limb, and active, contractile function was observed in all vessels. As demonstrated, near-infrared fluorescence lymphatic imaging enables the clinical assessment of lymphatics in lymphovenous malformations.
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Project description:PurposeThe aim of this study was to develop and characterize a novel peptide imaging agent for noninvasive near-infrared fluorescence imaging of protein transport by the lymphatics. An imaging agent consisting of a cyclic albumin-binding domain (cABD) peptide, with sequence, Arg-Leu-Ile-Glu-Asp-Ile-Cys-Leu-Pro-Arg-Trp-Gly-Cys-Leu-Trp-Glu-Asp-Asp-Lys, was conjugated to a near-infrared fluorophore, IRDye800CW, allowing for enhanced vascular uptake, retention, and fluorescence imaging.ProcedureCharacterization of the cABD-IRDye800 peptide conjugate was performed using fluorescence spectroscopy to assess optical properties and SDS-PAGE and Biacore binding assays to determine binding affinity and specificity. Fluorescence imaging of normal C57BL/6 mice was conducted to monitor lymphatic uptake and retention.ResultscABD-IRDye800 exhibited approximately six times greater fluorescent yield and greater stability than indocyanine green, an agent previously used in humans to image lymphatic vasculature. The agent exhibited affinity for albumin with IC(50) and Kd in the nanomolar range and demonstrated superior retention characteristics within mouse lymphatics when compared with IRDye800CW.ConclusionscABD-IRDye800 has utility for assessing lymphatic function in mouse models of human lymphatic disease and the potential for use in clinical diagnostic imaging of the lymphatic vasculature.
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