In vivo molecular-genetic imaging: multi-modality nuclear and optical combinations.

Multi-modality, noninvasive in vivo imaging is increasingly being used in molecular-genetic studies and will soon become the standard approach for reporter gene imaging studies in small animals. The coupling of nuclear and optical reporter genes, as described here, represents only the beginning of a far wider application of this technology in the future. Optical imaging and optical reporter systems are cost-effective and time-efficient; they require less resources and space than PET or MRI, and are particularly well suited for imaging small animals, such as mice. Optical reporter systems are also very useful for the quantification and selection of transduced cells using FACS, and for performing in vitro assays to validate the function and sensitivity of constitutive and specific-inducible reporter systems. However, optical imaging techniques are limited by depth of light penetration and do not yet provide optimal quantitative or tomographic information. These issues are not limiting for PET- or MRI-based reporter systems, and PET- and MRI-based animal studies are more easily generalized to human applications. Many of the shortcomings of each modality alone can be overcome by the use of dual- or triple-modality reporter constructs that incorporate the opportunity for PET, fluorescence and bioluminescence imaging.