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

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.