Cancer imaging: Gene transcription-based imaging and therapeutic systems

Abstract

Molecular-genetic imaging of cancer is in its infancy. Over the past decade gene reporter systems have been optimized in preclinical models and some have found their way into the clinic. The search is on to find the best combination of gene delivery vehicle and reporter imaging system that can be translated safely and quickly. The goal is to have a combination that can detect a wide variety of cancers with high sensitivity and specificity in a way that rivals the current clinical standard, positron emission tomography with [18F]fluorodeoxyglucose. To do so will require systemic delivery of reporter genes for the detection of micrometastases, and a nontoxic vector, whether viral or based on nanotechnology, to gain widespread acceptance by the oncology community. Merger of molecular-genetic imaging with gene therapy, a strategy that has been employed in the past, will likely be necessary for such imaging to reach widespread clinical use.

Tumor‐specific expression and detection of a CEST reporter gene

“…The latter can be accomplished by using a target‐selective promoter to drive the expression of a reporter following systemic delivery of a reporter plasmid. Many promoters of genes with elevated expression in human cancers have been examined as potential cancer‐specific promoters, but most are active only in cancers of certain tissues of origin . The optimal promoters for cancer‐specific, molecular‐genetic imaging would be active in a variety of human cancers, while remaining minimally active or silent in normal tissues.…”

Illuminating Cancer Systems with Genetically Engineered Mouse Models and Coupled Luciferase ReportersIn Vivo

“…An inherent constraint to the development of conventional injectable agents is that the details of synthesizing, labeling and validating a new and different ligand for every new receptor or protein of interest impose long cycle times on development. However, genetically-encoded reporters offer more modular tools for preclinical research, which once cloned into appropriate vectors and biologically confirmed, can be quickly applied to a broad array of applications with minimal modification (22, 24). While genetically-encoded imaging reporters are under development for use in humans, the potential for immunogenicity and transduction inefficiencies raise unique challenges (25).…”

Toward nanotechnology-based solutions for a particular disease: ovarian cancer as an example

“…Molecular imaging techniques target particular cancerassociated cell markers either on the cell surface or intracellular markers such as intracellular signaling molecules or may even target gene expression [53][54][55]. Examples of such markers in ovarian cancer are folate receptor α and CA125.…”