In Vivo Imaging of Single Tumor Cells in Fast-Flowing Bloodstream Using Near-Infrared Quantum Dots and Time-Gated Imaging

Abstract
While in vivo fluorescence imaging of cells immobilized within tissues provides a valuable tool to a broad range of biological studies, it still lacks the sensitivity required to visualize isolated cells circulating fast in the blood stream, due in particular to the autofluorescence from endogenous fluorophores. Time-gated imaging of near infrared emitting ZnCuInSe/ZnS quantum dots (QD) with fluorescence lifetimes in the range of 150-300 ns enables efficient rejection of fast autofluorescence photons and selection of QD fluorescence photons, thus significantly increasing sensitivity. We labeled model erythrocytes as well as lymphoma cells using these QD coated with a stable zwitterionic polymer surface chemistry. After reinjection in the blood stream, we were able to image and count individual QD-labeled cells circulating at mm∙s-1 velocities in blood vessels.