We report here the in vivo diagnostic use of a peptide-dye conjugate consisting of a cyanine dye and the somatostatin analog octreotate as a contrast agent for optical tumor imaging. When used in whole-body in vivo imaging of mouse xenografts, indotricarbocyanine-octreotate accumulated in tumor tissue. Tumor fluorescence rapidly increased and was more than threefold higher than that of normal tissue from 3 to 24 h after application. The targeting conjugate was also specifically internalized by primary human neuroendocrine tumor cells. This imaging approach, combining the specificity of ligand/receptor interaction with near-infrared fluorescence detection, may be applied in various other fields of cancer diagnosis.
The cooling of vibrationally hot azulene is studied in different solvents by picosecond spectroscopy. Excitation to the electronic S1 state generates molecules with a vibrationally hot ground state by rapid internal conversion. The subsequent cooling is monitored by the temperature-dependent change of the S0–S1 absorption edge and occurs via interaction with the solvent on a time scale of several tens of picoseconds. A theoretical model of intermolecular energy transfer in the liquid phase is developed. The vibrational excess energy of azulene is transferred to the solvent molecules by isolated binary collisions, where the multimode vibrational system of the molecules is considered explicitly. The dissipation of energy within the solvent is simulated by the macroscopic conduction of heat. The temporal development of the vibrational temperature of the azulene molecules and the concommitant changes of absorption are calculated taking into account the properties of the specific solvent. The results of the theory show quantitative agreement with our data.
We have developed diffusely scattering solid phantoms with optical (scattering) properties amenable to theoretical calculations. Monodisperse quartz glass spheres were used as scatterers embedded in polyester resin. An infrared dye was added to simulate absorption by biological tissue. Solid phantoms were tested for their macroscopic homogeneity. Several phantoms were built with well-defined spatial variations in their transport scattering and absorption coefficients to be used for optical tomography. Scattering, transport scattering, and absorption coefficients of solid, homogeneous phantoms and of aqueous suspensions of monodisperse quartz glass spheres were derived from measurements of time-integrated collimated transmittance and time-resolved diffuse transmittance. For aqueous suspensions of monodisperse quartz glass spheres at known number density scattering and transport scattering coefficients calculated by Mie theory are in quantitative agreement with experimentally derived values. In addition, diffuse reflectance and diffuse transmittance of aqueous suspensions at various number densities were measured and found to be in excellent agreement with results of Monte Carlo calculations using theoretical values for the scattering coefficients and anisotropy parameters.
Abstract. We compare pharmacokinetic, tolerance, and imaging properties of two near-IR contrast agents, indocyanine green (ICG) and 1,1 -bis-(4-sulfobutyl) indotricarbocyanine-5,5 -dicarboxylic acid diglucamide monosodium salt (SIDAG). ICG is a clinically approved imaging agent, and its derivative SIDAG is a more hydrophilic counterpart that has recently shown promising imaging properties in preclinical studies. The rather lipophilic ICG has a very short plasma half-life, thus limiting the time available to image body regions during its vascular circulation (e.g., the breast in optical mammography where scanning over several minutes is required). In order to change the physicochemical properties of the indotricarbocyanine dye backbone, several derivatives were synthesized with increasing hydrophilicity. The most hydrophilic dye SIDAG is selected for further biological characterization. The acute tolerance of SIDAG in mice is increased up to 60-fold compared to ICG. Contrary to ICG, the pharmacokinetic properties of SIDAG are shifted toward renal elimination, caused by the high hydrophilicity of the molecule. N-Nitrosomethylurea (NMU)-induced rat breast carcinomas are clearly demarcated, both immediately and 24 h after intravenous administration of SIDAG, whereas ICG shows a weak tumor contrast under the same conditions. Our findings demonstrate that SIDAG is a high potential contrast agent for optical imaging, which could increase the sensitivity for detection of inflamed regions and tumors. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).
Macromolecules accumulate in solid tumors and can thus be used as carriers for the delivery of attached contrast agents to tumors. We report the synthesis and use of serum protein-dye conjugates consisting of transferrin (Tf) or human serum albumin (HSA) and an indotricarbocyanine (ITCC) derivative as contrast agents for the optical imaging of tumors. The compounds were characterized with respect to their photophysical properties and tested in vitro for their ability to bind to tumor cells and in vivo for their potential to delineate experimental tumors. In contrast to HAS-ITTC, Tf-ITCC showed receptor-mediated uptake by HT29 human colon cancer cells in vitro. After intravenous injection into HT29 tumor-bearing nude mice both compounds induced increased fluorescence contrast of tumors in vivo. After 24 h the contrast between tumor and normal tissue was significantly higher for Tf-ITCC than for HAS-ITCC. Dye-induced fluorescence was found to be predominantly located in perinecrotic areas of the tumor. Furthermore, Tf-ITCC produced fluorescence of viable tumor cells, whereas HAS-ITCC fluorescence was recorded along connective tissue. We conclude that ITCC-labeled Tf and HSA can serve as macromolecular contrast agents for the optical imaging of tumors, with Tf-ITCC showing higher efficiency.
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