1H NMR spectroscopy of subcutaneous tumors in mice: Preliminary studies of effects of growth, chemotherapy and blood flow reduction

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Abstract
This study evaluates a number of methods for obtaining 1H NMR spectra with adequate suppression of lipid and water resonances in two subcutaneously implanted transplantable tumor models (RIF-1 and EMT6/SF). Spin-echo spectra with long TEs (270 ms; water suppressed by presaturation) eliminated lipid resonances from 1H spectra of RIF-1 and decreased lipid contamination in spectra of EMT6/SF; however, spectral sensitivity was substantially reduced. A shorter TE (135 ms) increased sensitivity but did not result in adequate suppression of the lipid peaks. In RIF-1, but not EMT6/SF, adequate lipid suppression was achieved by: (i) spatially selective presaturation of lipid, which in this tumor (but not in EMT6/SF) was localized in a thin region along the periphery of the tumor, followed by a 1-D spin-echo chemical shift imaging pulse sequence (TE = 135 ms); and (ii) 2-D spin-echo chemical shift imaging (TE = 270 ms; ∼2 × 2 × 9 mm3 voxels). Preliminary 1H studies of the RIF-1 tumor indicate that: (i) there are no significant changes in metabolite levels relative to tumor water during 4 days of untreated tumor growth; (ii) tumor response to chemotherapy with 5-fluorouracil results in a decrease in intensity of all metabolite 1H resonances relative to tumor water, with total choline decreasing the most and lactate the least; and (iii) acute tumor blood flow reduction induced by administration of hydralazine results in doubling of the lactate intensity relative to water. These experiments demonstrate that in vivo 1H spectroscopy is feasible in at least one commonly employed subcutaneous tumor model (RIF-1) and that this nucleus holds considerable promise for clinical and experimental studies of tumors.
Funding Information
  • National Institutes of Health (CA51950, CA51935)