Journal
BIOCONJUGATE CHEMISTRY
Volume 21, Issue 10, Pages 1811-1819Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc1001328
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Funding
- Howard Hughes Medical Institute (HHMI)
- Department of Defense Breast Cancer Research [W81XWH-05-1-0183]
- Canadian Institute of Health Research (CIHR) [MFE 83832]
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We combine a novel boronate trap for F- with a near-infrared fluorophore into a single molecule. Attachment to targeting ligands enables localization by positron emission tomography (PET) and near-infrared fluorescence (NIRF). Our first application of this generic tag is to label Lymphoseek (tilmanocept), an agent designed for receptor-specific sentinel lymph node (SLN) mapping. The new conjugate incorporates F-18(-) in a single, aqueous step, targets mouse SLN rapidly (1 h) with reduced distal lymph node accumulation, permits PET or scintigraphic imaging of SLN, and enables NIRF-guided excision and histological verification even after F-18 decay. This embodiment is superior to current SLN mapping agents such as nontargeted [Tc-99m]sulfur colloids and Isosulfan Blue, as well as the phase III targeted ligand [Tc-99m]SPECT Lymphoseek counterpart, species that are visible by SPECT or visible absorbance separately. Facile incorporation of F-18 into a NIRF probe should promote many synergistic PET and NIRF combinations.
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