Antisense and nuclear medicine

Abstract

Despite many uncertainties concerning mechanism, synthetic single-strand antisense deoxyribonucleic acids (DNAs) are now in clinical trials for the chemotherapy of viral infections such as human immunodeficiency virus (HIV) and human papilloma virus; several cancers, including follicular lymphoma and acute myelogenous leukemia; inflammatory processes such as Crohn's disease and rheumatoid arthritis and in allergic disorders. There are approximately 10 trials, and early results are generally encouraging. Therefore, the expectation is that antisense DNAs will be important to future chemotherapy. The question considered here is whether antisense DNAs will also be important to future nuclear medicine imaging. While efforts toward developing antisense imaging are comparatively nonexistent thus far, investigations into the mechanisms of cellular transport and localization and the development of a second generation of antisense DNAs have occurred largely within the antisense chemotherapy industry. Fortunately, many of the properties of DNA for antisense imaging, such as high in vivo stability and adequate cell membrane transport, are the same as those for antisense chemotherapy. Unfortunately, interests diverge in the case of several other key properties. For example, rapid localization and clearance kinetics of the radiolabel and prolonged retention in the target are requirements unique to nuclear medicine. No doubt the development of antisense imaging will continue to benefit from improvements in the antisense chemotherapy industry. However, a considerable effort will be required to optimize this approach for imaging (and radiotherapy). The potential of specifically targeting virtually any disease or normal tissue should make this effort worthwhile.