Mice are widely used for human tumor xenograft studies of cancer development and drug efficacy and toxicity. Stable isotope tracing coupled with metabolomic analysis is an emerging approach for assaying metabolic network activity. In mouse models there are several routes of tracer introduction, which have particular advantages and disadvantages that depend on the model and the questions addressed. This protocol describes the bolus i.v. route via repeated tail vein injections of solutions of stable isotope enriched tracers including 13C6-glucose and 13C5,15N2-glutamine. Repeated injections give higher enrichments and over longer labeling periods than a single bolus. Multiple injections of glutamine are necessary to achieve adequate enrichment in engrafted tumors.
The work has been supported by NIH Grants 1R01CA118434-01A2, NIH 5R01ES022191-04, NIH 3R01ES022191-04S1 (to TWMF), R01CA-086412 and RO1 CA150947 (to JY), NIH R21CA133688 (to ANL), NIH P01 CA163223 (to ANL, TWMF and JY), and NIH 1U24DK097215-01A1 (to TWMF, ANL), the Kentucky Challenge for Excellence, and the Susan G. Komen Foundation BCTR0503648.
Lane, Andrew N.; Yan, Jun; and Fan, Teresa W-M, "13C Tracer Studies of Metabolism in Mouse Tumor Xenografts" (2015). Toxicology and Cancer Biology Faculty Publications. 45.