The technique of non-invasive optical imaging is based on the principle that when a dye is exposed to light it absorbs energy and is elevated from the steady state to a high-energy state. To return to its normal, low-energy state, the molecule releases energy in the form of photons with wavelengths that are either in the visible (400–700 nm) or the near infrared (NIR; 700–900 nm) range (1). Although both types of dyes can be used for imaging, in general NIR agents are favored over those functional in the visible range because fluorescence from NIR probes can be detected in deep tissue, have low autofluorescence, and generate low background signals because tissues do not absorb in the NIR wavelength range (2). Among the various NIR agents, only one, indocyanine green (ICG; also known as IR-125 or Cardiogreen), with absorption at ~780 nm and emission at ~820 nm, is approved by the United States Food and Drug Administration (US FDA) for clinical applications (3) and is under evaluation in several clinical trials for other applications. ICG is a tricarbocyanine dye that is fluorescent only in the free state and easily binds to proteins through non-covalent linkages (such as ionic, hydrophobic, electrostatic, or hydrogen bonds). When bound to proteins ICG is non-fluorescent, but on dissociation from the protein complex it reverts to the fluorescent state and the signal has been shown to be suitable for imaging (4). The interleukin-2 (IL-2) receptor (IL2R) consists of three subunits (α, β, and γ) that are non-covalently linked. Among these subunits, the γ-chain is a constitutive component of the cell membrane, but the α- (also known as CD25) and β-chains have to be induced by IL-2 and other related ligands to bring about functionality to the receptor (5). The functions of the various subunits of IL2R and the signaling pathways used to mediate its activity are described elsewhere (5). Induction of the α-chain is believed to impart specificity to the receptor and indicates activation of the T cells and dendritic cells that participate in the development of an immune response and play a role in the progression of various malignancies and autoimmune diseases (6, 7). Once activated, the receptor-ligand complex is internalized by the cell for inactivation through enzymatic digestion in the lysosomes (8, 9). Because of its possible role in the development of allograft rejection, cancer, autoimmune diseases, etc., daclizumab (Dac), a commercially available humanized monoclonal antibody (MAb) directed toward the IL2R α-chain, is approved by the US FDA to prevent or treat renal allograft rejection (10). It is also under investigation in several clinical trials for the treatment of a variety of ailments, including cancer. The characteristic properties of ICG (fluorescent only in an unbound state) and the IL2R α-chain (internalization by the cell) prompted Ogawa et al. to develop an imaging probe for cancer by complexing ICG to Dac (Dac-ICG) (4). The investigators used the Dac-ICG complex to image cells that express the IL2R α-chain under conditions and showed that the complex could also be used for the imaging of IL2R α-chain–expressing xenograft tumors in mice.