Imaging transgene expression with radionuclide imaging technologies

A variety of imaging technologies are being investigated as tools for study ing gene expression in living subjects, Noninvasive, repetitive and quantit ative imaging of gene expression will help both to facilitate human gene th erapy trials and to allow for the study of animal models of molecular and c ellular therapy, Radionuclide approaches using single photon emission compu ted tomography (SPECT) and positron emission tomography (PET) are the most mature of the current imaging technologies and offer many advantages for im aging gene expression compared to optical and magnetic resonance imaging (M RI)-based approaches. These advantages include relatively high sensitivity, full quantitative capability (for PET), and the ability to extend small an imal assays directly into clinical human applications, We describe a PET sc anner (microPET) designed specifically for studies of small animals. We rev iew "marker/reporter gene" imaging approaches using the herpes simplex type 1 virus thymidine kinase (HSV1-tk) and the dopamine type 2 receptor (D2R) genes. We describe and contrast several radiolabeled probes that can be use d with the HSV1-tk reporter gene both for SPECT and for PET imaging. We als o describe the advantages/disadvantages of each of the assays developed and discuss future animal and human applications.