The influence of chemical structure of DNA and other oligomer radiopharmaceuticals on tumor delivery.
Deoxyribose nucleic acids (DNAs) and their many chemically distinct synthetic analogs (collectively 'oligomers') provide a rich variety of molecules with different properties, each attractive as a potential drug. The main impediment to the successful development of these drugs is often identified as its delivery. Delivery usually refers to the cell membrane transport required to bring the oligomer into the cytoplasm or nucleus and therefore into the vicinity of the mRNA target (antisense and RNA interference technology) or DNA target (gene therapy). Since these drugs are intended for systemic administration in most cases, the term 'delivery' should be expanded to include pharmacokinetics as woell. However, most studies of nonradioactive drugs emphasize pharmacology and efficacy at the expense of pharmacokinetics. Fortunately, by tracing radioactivity in the living subject, the development of radiopharmaceuticals for nuclear imaging is providing valuable data on pharmacokinetics as well as cell membrane transport of a limited, but important number of oligomers, primarily in connection with antisense therapy and pretargeting of tumors. This review is concerned with the influence of chemical structure on the delivery properties of radiolabeled oligomers primarily for nuclear imaging studies and largely in mouse models of tumors.
Hnatowic
Donald J
DJ
Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. donald.hnatowich@umassmed.edu
Nakamura
Kayoko
K
D000818:Animals; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism*; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy; D006801:Humans; D007553:Isotope Labeling; D012333:RNA, Messenger / Q000235:genetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D004247:DNA