Molecular MR Imaging of Cancer Gene Therapy: Ferritin Transgene Reporter Takes the Stage

Abstract

Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic e‹cacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene.

Magnetic Resonance Imaging of Tumors Colonized with Bacterial Ferritin-Expressing Escherichia coli

“…Recent studies successfully tested the potential of magnetotactic bacteria ( Magnetospirillum magneticum ) or one of their genes ( magA ) for the detection of tumors [47], [48], as well as the human H-chain ferritin as a reporters for non-invasive MRI of mammalian cells in different applications [23], [24], [25], [26], [27], [28], [29], [30], [31]. Here we report, for the first time, the evaluation of bacterial ferritin-like genes (namely bfr , fri , and ftn ) as MRI reporter genes expressed in prokaryotic organisms.…”

“…In MRI transverse relaxation (T2) is shortened by the presence of iron and its reciprocal, known as R2 is directly proportional to iron concentration. Expression of human H-chain ferritin can be used to generate contrast in T2 weighted MRI in vivo [23], [24], [25], [26], [27], [28], [29], [30], [31], causing a local reduction in the signal intensity. The iron loading of human ferritin, which has been intensively studied at different magnetic field strengths, results in changes to the longitudinal ( R 1  = 1/ T 1 ) and transverse ( R 2  = 1/ T 2 ) relaxation rates of water [32], [33].…”

Imaging Mouse Cancer Models In Vivo Using Reporter Transgenes

“…Tumor models have been a popular choice for proof-of-concept studies for novel MR reporters as they provide a large imageable mass in vivo and as cancer cells are in general easy to grow and genetically modify. Perhaps there has been a resulting tendency to assume that MR reporters could be of use in answering relevant questions about tumor biology (Hasegawa et al 2010), but this is not necessarily the case. For example, the utility of ferritin, or indeed any of the several iron-based MR reporter systems (Weissleder et al 1997(Weissleder et al , 2000Deans et al 2006;Zurkiya et al 2008;Cui et al 2010) with regard to cancer, might be limited by the fact that a perturbed iron metabolism is a feature of many tumor types; iron-import proteins are up-regulated and iron-storage proteins (ferritin) down-regulated (Gatter et al 1983;Hogemann-Savellano et al 2003;Herbison et al 2009;Okazaki et al 2010).…”

Magnetic Resonance Reporter Gene Imaging

“…Molecular imaging encompasses the fields of chemistry, biology, physics, and medicine, and brings experts in these scientific fields together to determine means of visualizing molecular and cellular events 1, 2…”