Merging molecular imaging and RNA interference: Early experience in live animals

Abstract

The rapid development of non-invasive imaging techniques and imaging reporters coincided with the enthusiastic response that the introduction of RNAi (RNA interference) techniques created in the research community. Imaging in experimental animals provides quantitative or semi-quantitative information regarding the biodistribution of small interfering RNAs and the levels of gene interference (i.e. knockdown of the target mRNA) in living animals. In this review we give a brief summary of the first imaging findings that have potential for accelerating the development and testing of new approaches that explore RNAi as a method for achieving loss-of-function effects in vivo and as a promising therapeutic tool.

Imaging CXCR4 Expression with 99mTc-Radiolabeled Small-Interference RNA in Experimental Human Breast Cancer Xenografts

“…Therefore, a noninvasive, convenient, and inexpensive technique for tracing the delivery of siRNAs in vivo is essential. Among several tracing agents developed in recent years, siRNA radiolabeling has attracted attention for its ability to localize and quantify siRNAs using noninvasive imaging methods [24,25].…”

Metabolism Studies of Unformulated Internally [3H]-Labeled Short Interfering RNAs in Mice

“…Understanding siRNA biodistribution and biostability is essential for their development as therapeutics. Although a variety of nonisotopic labeling techniques exist (e.g., bioluminescence and fluorescence) (Bogdanov, 2008;Moore and Medarova, 2009), the use of 3 H-radiolabeled oligonucleotides to perform (pre)-clinical in vitro and/or in vivo studies offers a distinct advantage of avoiding chemical and structural modifications.…”

Noninvasive Visualization of RNA Delivery with 99mTc-Radiolabeled Small-Interference RNA in Tumor Xenografts

“…Compared with these optical methods, radionuclide tracing methods have great advantages such as high sensitivity, quantitative determination, availability in large animals, and promising clinical application (6). When radiolabeled with g-or positron-emitting isotopes, siRNA is able to show its location, quantity, and duration by noninvasive imaging (7). Moreover, radiolabeled with g-and b-emitting isotopes such as 131 I, siRNA probes can achieve the dual effect of imaging and therapy.…”