Nuclear molecular imaging: a novel means of drug discovery in gene therapy?

Abstract

The next step for medical imaging is molecular imaging. Nuclear imaging with its extremely high sensitivity is well suited to target molecular structures. Nuclear imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can measure transgene expression in living animals using appropriate reporter gene-reporter probe systems. One such system uses the herpes simplex virus (HSV) thymidine kinase (HSV-1-tk) gene as reporter gene and radiolabeled guanosine analogues such as aciclovir, ganciclovir and penciclovir as substrates. Another system uses receptor genes as reporter gene and receptor-targeting radiolabeled agents such as spiperone and octreotide as probe. In addition, sodium/iodide symporter gene expression can be monitored by iodide uptake and may well serve as a suitable system to obtain quantitative information on gene expression. This new methodology provides temporal quantitative data on biodistribution and pharmacological action, without the need to sacrifice numerous animals. In this way, nuclear molecular imaging may reduce the time of development and testing of new drugs involved in gene therapy and may therefore represent a cost-saving strategy.