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 [(18)F]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.

Figure 1. Criteria to consider when developing a reporter transcription-based cancer imaging system

Figure 2. Trends in publication on reporter gene expression-based cancer imaging (and therapy)

(a) The number of publications on gene transcription-based imaging systems each year over the last decade. The Search terms “(cancer or tumor) and specific and promoter and imaging” and “(cancer or tumor) and specific and promoter and imaging and therapy” were used for PubMed database research. Only publications that contain in vivo preclinical testing were included. (b) Promoters used for cancer imaging in 65 publications shown in (a). (Abbreviations: PSA, prostate-specific antigen; hTERT, human telomerase reverse transcriptase; AFP, α-fetoprotein; CEA, carcinoembryonic antigen; P0, myelin protein zero; hAAT, human α-1-antitrypsin; CCKAR, cholecystokinin type A receptor; ERE, oestrogen-responsive element; HIP, hepatocarcinoma-intestine-pancreas; HRE, hypoxia-responsive element; Id1, inhibitor of DNA binding-1; rNIS, rat sodium iodide symporter; and, PEG-3, progression elevated gene-3).