Molecular Optical Probes for Imaging Tumors

摘要

Biomedical optical methods provide distinctly new diagnostic capabilities while complementing conventional imaging modalities. Some advantages of optical methods include the use of non-ionizing radiation, detection of minute amounts of light-absorbing materials in tissue models, capability of continuous data acquisition for real-time monitoring, and the potential availability of low cost, user friendly, and portable imaging systems and endoscopes. While many human diseases have been studied successfully by using intrinsic optical properties of normal and pathologic tissues, molecular imaging of the expression of aberrant genes, proteins, and other pathophysiologic processes would be enhanced by the use of highly specific exogenous molecular probes. In addition to enhancing the specificity and sensitivity of detecting and imaging various diseases, optical molecular probes are less dependent on inter- and intra-species variations. They can also furnish unique information regarding the functional status of diseases. Recent review articles have described the development and application of various optical molecular probes in biomedical research. These include bioluminescent reporters, fluorescent proteins, protease-sensitive optical probes, nanoparticles, quantum dots, and general overview of the trends in contrast-mediated optical imaging of tumors. To be effective, the molecular probes should produce detectable, quantifiable and discernable signals in response to light absorption or biological activation. In addition, optimizing the in vivo stability, biocompatibility and pharmacokmetics is necessary for their use in living mammals. Presently, fluorescein, indocyanine green (ICG) and fluorescent photosensitizers are widely used as optical molecular probes for in vivo imaging of tumors, possibly due to their established photophysical properties and safety profile in humans. Accordingly, we have developed a library of near infrared molecular probes that target tumors by receptor-mediated endocytosis. We recently used this approach to target the expression of integrins in tumors and to monitor the functional status of highly metabolizing cells in vivo. As shown in Figure 1, a peptide containing the ROD sequence is clearly retained in αvβ3 receptor-positive human lung tumor model implanted in nude mice. Competitive blocking studies showed that the uptake is receptor-specific.