Nuclear Magnetic Resonance (NMR) Spectroscopy in the Study of Whole‐animal Metabolism

Abstract

NMR‐active isotopes are present in living systems and, because the radiofrequency of nuclear magnetic resonance experiments is non‐ionizing, NMR signals can be obtained noninvasively and nondestructively from whole living organisms.

Keywords: non‐invasive; in vivo; isotopomer; isotope

Figure 1.

ISIS‐localized 31P MR spectrum, obtained at 4.7 T from MCF‐7 human breast cancer xenograft growing in the mammary fat pad of a SCID mouse. Spectral volume was 1 cm3 and acquisition time was 30 min. Abbreviations: 3‐APP, 3‐aminopropylphosphonate; PEtn, phosphoethanolamine; PCho, phosphocholine; Pi, inorganic phosphate; GPC, glycerophosphorylcholine; PCr, phosphocreatine; γ‐,α‐,β‐ NTP, terminal, primary and middle phosphates of nucleoside triphosphates (e.g. GTP, ATP). Prior to spectroscopy, the mouse was injected with 3‐APP, a nontoxic extracellular pH marker. Intra‐ and extracellular pH values are determined from the chemical shifts of Pi and 3‐APP, respectively.

Figure 2.

Images of a 12‐mm‐thick axial section using identical fields‐of‐view from a human patient, acquired at a field strength of 1.5 T. (a) Conventional T2‐weighted fast spin echo MRI. (b) Conventional postcontrast T1‐weighted MRI. (c) Map of choline intensities. (d) Image of the apparent water diffusion coefficient. The spectroscopic image (c) was acquired with a repetition time of 2.3 s and an echo time of 272 ms, and is shown at the nominal volume resolution (10 × 10 × 12 mm) without smoothing. Courtesy of J.R. Alger, Department of Radiology, UCLA.

Figure 3.

19F spectra from tumours of HT‐29 human colon cancer cells growing in Nude mice treated with 5‐fluorocytosine. Spectrum (a) was obtained from tumours of control HT‐29neo cells. Spectrum (b) was obtained from tumours of HT‐29 cells transfected with the cytidyltransferase gene from Saccharomyces cerevisiae. Surface coillocalized spectra were obtained from volumes of approximately 1 cm × 1 cm × 1 cm in an acquisition time of 12 min. Abbreviations: 5‐FC, 5‐fluorocytosine; 5‐FU, 5‐fluorouracil; FNuc, fluorinated nucleotides; FβAl, fluoro‐β‐D‐alanine. Reprinted with permission from Stegman LD, Rehemtulla A, Beattie B et al. (1999) Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy. Proceedings of the National Academy of Sciences of the USA96: 9821–9826.

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Further Reading

Gadian D (1982) NMR and its Applications to Living Systems. Oxford: Oxford University Press.

Gillies RJ (ed.) (1994) NMR and its Application to Physiology and Biomedicine. Orlando: Academic Press.

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Gillies, Robert J, and Raghunand, Natarajan(Apr 2001) Nuclear Magnetic Resonance (NMR) Spectroscopy in the Study of Whole‐animal Metabolism. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003102]