Yann Jamin1, Simon P. Robinson1, Martin O. Leach1, Thomas R. Eykyn1
1Institute of Cancer Research and Royal
Marsden NHS trust, Sutton, UK
The yeast cytosine deaminase (CD) is used in cancer chemotherapy to activate selectively the nontoxic prodrug 5-Fluorocytosine (5-FC) into the toxic antimetabolite 5-Fluorouracil (5-FU) in tumours. Employing Dynamic Nuclear Polarization (DNP) and 13C MRS, we demonstrate that both 5-FC and 5-FU are readily hyperpolarizable, demonstrate long T1 (> 20s, at 11.7T) and a appreciable 13C chemical shift difference of ~ 5ppm. This results encourage further investigation on the use of hyperpolarized 13C MRS to monitor CD-mediated activation of 5-FU in vivo as well as other Fluoropyrimidine-based chemotherapy strategies.
Keywords