Detection of transgene expression using hyperpolarized 13C urea and diffusion-weighted magnetic resonance spectroscopy.

Abstract:: Purpose To assess the potential of a gene reporter system, based on a urea transporter (UTB) and hyperpolarized [¹³C]urea. Methods Mice were implanted subcutaneously with either unmodified control cells or otherwise identical cells expressing UTB. After injection of hyperpolarized [¹³C]urea, a spin echo sequence was used to measure urea concentration, T1, and diffusion in control and UTB-expressing tissue. Results The apparent diffusion coefficient of hyperpolarized urea was 21% lower in tissue expressing UTB, in comparison with control tissue (P<0.05, 1-tailed t-test, n=6 in each group). No difference in water apparent diffusion coefficient or cellularity between these tissues was found, indicating that they were otherwise similar in composition. Conclusion Expression of UTB, by mediating cell uptake of urea, lowers the apparent diffusion coefficient of hyperpolarized ¹³C urea in tissue and thus the transporter has the potential to be used as a magnetic resonance-based gene reporter in vivo.

Authors:: PS Patrick, MI Kettunen, S-S Tee, TB Rodrigues, E Serrao, KN Timm, S McGuire, KM Brindle

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