Shortening of apparent transverse relaxation time of inorganic phosphate as a breast cancer biomarker

van der Kemp, Wybe J M, van der Velden, Tijl A, Schmitz, Alexander M, Gilhuijs, Kenneth G, Luijten, Peter R, Klomp, Dennis W J, Wijnen, Jannie P


NMR in Biomedicine p. e4011


Phosphorus MRS offers a non-invasive tool for monitoring cell energy and phospholipid metabolism and can be of additional value in diagnosing cancer and monitoring cancer therapy. In this study, we determined the transverse relaxation times of a number of phosphorous metabolites in a group of breast cancer patients by adiabatic multi-echo spectroscopic imaging at 7 T. The transverse relaxation times of phosphoethanolamine, phosphocholine, inorganic phosphate (Pi ), glycerophosphocholine and glycerophosphatidylcholine were 184 ± 8 ms, 203 ± 17 ms, 87 ± 8 ms, 240 ± 56 ms and 20 ± 10 ms, respectively. The transverse relaxation time of Pi in breast cancer tissue was less than half that of healthy fibroglandular tissue. This effect is most likely caused by an up-regulation of glycolysis in breast cancer tissue that leads to interaction of Pi with the GAPDH enzyme, which forms part of the reversible pathway of exchange of Pi with gamma-adenosine tri-phosphate, thus shortening its apparent transverse relaxation time. As healthy breast tissue shows very little glycolytic activity, the apparent T2 shortening of Pi due to malignant transformation could possibly be used as a biomarker for cancer.