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 ¹⁸F⁻ 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 ¹⁸F decay. This embodiment is superior to current SLN mapping agents such as nontargeted [^99mTc]sulfur colloids and Isosulfan Blue, as well as the phase III targeted ligand [^99mTc]SPECT Lymphoseek counterpart, species that are visible by SPECT or visible absorbance separately. Facile incorporation of ¹⁸F into a NIRF probe should promote many synergistic PET and NIRF combinations.