Imaging Techniques for Gene Therapy: SPECT,PET,and MRI

Abstract

Gene therapy by the transfer and expression of suicide genes is performed using genes coding for nonmammalian enzymes that transform nontoxic prodrugs into toxic metabolites. Employing radiolabeled specific substrates and scintigraphic procedures to determine the functional activity of the recombinant enzyme in vivo, a therapeutic window of maximal gene expression and consecutive drug administration may be defined. If the gene therapy approach is based on the transduction of receptor genes, the recombinant gene expression in tumor cells can be monitored with radiolabeled ligands. Transfer of transporter genes as the sodium iodide transporter may also lead to the visualization of transduction via accumulation of iodide or pertechnetate. Furthermore, imaging based on transchelation of oxotechnetate to a polypeptide motif from a biocompatible complex with a higher dissociation constant than that of a diglycilcysteine complex or tyrosinase gene transfer for metal ion scavenging have been described. In addition, therapy effects may be assessed by the evaluation of the morphological changes of the tumor using magnetic resonance imaging or, more effectively, by the measurement of changes in metabolism with positron emission tomography employing tracers of tumor metabolism and proliferation. Finally, enzyme or receptor genes may serve as noninvasive reporter genes, if applied in the context of bicistronic vectors leading to coexpression of the therapeutic gene and the noninvasive reporter gene.