We describe the development of multifunctional nanoparticle probes based on semiconductor quantum dots (QDs) for cancer targeting and imaging in living animals. The structural design involves encapsulating luminescent QDs with an ABC triblock copolymer and linking this amphiphilic polymer to tumor-targeting ligands and drug-delivery functionalities. In vivo targeting studies of human prostate cancer growing in nude mice indicate that the QD probes accumulate at tumors both by the enhanced permeability and retention of tumor sites and by antibody binding to cancer-specific cell surface biomarkers. Using both subcutaneous injection of QD-tagged cancer cells and systemic injection of multifunctional QD probes, we have achieved sensitive and multicolor fluorescence imaging of cancer cells under in vivo conditions. We have also integrated a whole-body macro-illumination system with wavelength-resolved spectral imaging for efficient background removal and precise delineation of weak spectral signatures. These results raise new possibilities for ultrasensitive and multiplexed imaging of molecular targets in vivo.

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In vivo cancer targeting and imaging with semiconductor quantum dots

A Monte Carlo model of steady-state light transport in multi-layered tissues (MCML) has been coded in ANSI Standard C; therefore, the program can be used on various computers. Dynamic data allocation is used for MCML, hence the number of tissue layers and grid elements of the grid system can be varied by users at run time. The coordinates of the simulated data for each grid element in the radial and angular directions are optimized. Some of the MCML computational results have been verified with those of other theories or other investigators. The program, including the source code, has been in the public domain since 1992.

MCML-Monte Carlo modeling of light transport in multi-layered tissues

MCML—Monte Carlo modeling of light transport in multi-layered tissues

In vivo near-infrared fluorescence imaging

Photoacoustic imaging (also called optoacoustic or thermoacoustic imaging) has the potential to image animal or human organs, such as the breast and the brain, with simultaneous high contrast and high spatial resolution. This article provides an overview of the rapidly expanding field of photoacoustic imaging for biomedical applications. Imaging techniques, including depth profiling in layered media, scanning tomography with focused ultrasonic transducers, image forming with an acoustic lens, and computed tomography with unfocused transducers, are introduced. Special emphasis is placed on computed tomography, including reconstruction algorithms, spatial resolution, and related recent experiments. Promising biomedical applications are discussed throughout the text, including (1) tomographic imaging of the skin and other superficial organs by laser-induced photoacoustic microscopy, which offers the critical advantages, over current high-resolution optical imaging modalities, of deeper imaging depth and higher absorptioncontrasts, (2) breast cancerdetection by near-infrared light or radio-frequency–wave-induced photoacoustic imaging, which has important potential for early detection, and (3) small animal imaging by laser-induced photoacoustic imaging, which measures unique optical absorptioncontrasts related to important biochemical information and provides better resolution in deep tissues than optical imaging.

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Photoacoustic imaging in biomedicine

The known optical properties (absorption, scattering, total attenuation, effective attenuation, and/or anisotropy coefficients) of various biological tissues at a variety of wavelengths are reviewed. The theoretical foundations for most experimental approaches are outlined. Relations between Kubelka-Munk parameters and transport coefficients are listed. The optical properties of aorta, liver, and muscle at 633 nm are discussed in detail. An extensive bibliography is provided. >

W.F. Cheong

Papers

A review of the optical properties of biological tissues