Imaging oncogene expression

Abstract

This review briefly outlines the importance of molecular imaging, particularly imaging of endogenous gene expression for noninvasive genetic analysis of radiographic masses. The concept of antisense imaging agents and the advantages and challenges in the development of hybridization probes for in vivo imaging are described. An overview of the investigations on oncogene expression imaging is given. Finally, the need for further improvement in antisense-based imaging agents and directions to improve oncogene mRNA targeting is stated.

Imaging Genetic Information

“…The ability to noninvasively image RNA in a patient would enable one to monitor disease states in which the disease state is associated with the expression of a unique gene, such as an oncogene [54], or a viral gene [55,56], or an overexpressed gene [57]. Antisense imaging of RNA could also be used to monitor the level and distribution of therapeutic genes in gene therapy or to monitor the effectiveness of therapeutic treatments that are based on suppressing gene expression.…”

“…Once a disease-specific mRNA sequence for a patient is identified, it would be straightforward, at least in principle, to design and synthesize a patient-specific antisense nucleic acid probe within days that can recognize and bind the RNA with high affinity by using only Watson-crick base-pairing rules. The problem at the moment is that currently available antisense oligonucleotides and analogs are membrane impermeable, and attempts to attach cell-targeting and cell-penetrating ligands to enable antisense imaging by PeT have not been very successful [54,58]. Thus, much of the development of antisense imaging agents has shifted to the design of the antisense delivery system and the use of optical turn-on probes that circumvent problems with membrane permeability.…”

Genomic Biomarkers for Molecular Imaging: Predicting the Future

“…More than 100 such specific oncogenes have been identified for various cancer types. CCND1 encodes cyclin D1 protein and the HER2 oncogene which is also known as ERBB2/neu, Her2 (5). …”

Native mRNA antisense-accessible sites library for the selection of antisense oligonucleotides, PNAs, and siRNAs

“…This library may also be useful for developing antisense-based mRNA imaging agents (Rodriguez et al 2007;Mukherjee et al 2009) and for constraining secondary structure predictions of native mRNAs (Chen 2008). Other factors, such as protein interactions and binding, may affect folding and accessibility of sites on mRNA in vivo and may explain variations in the effectiveness of the ps-ODN, PNA, and siRNA agents with sequence.…”

“…A more recent study has reached a conclusion concerning target site accessibility and the effectiveness of both siRNAs and microRNAs (miRNAs) (Obernosterer et al 2008). Likewise, antisense target accessibility should also be important for the effectiveness of fluorescent probes such as molecular beacons and positron emission tomography (PET) imaging agents (Rodriguez et al 2007;Mukherjee et al 2009), as well as for determining the folding of native mRNA (Chen 2008).…”