In vivo 5-fluorouracil and fluoronucleotide T1 relaxation time measurements using the variable nutation angle method

(19)Fluorine NMRS has the potential to enable noninvasive predictions of tumor response to 5-fluorouracil (5FU) therapy based on tumor pharmacokinetics. Knowledge of the T-1's of 5FU and its fluoronucleotide anabolites (FNuc) is required for quantitative spectral analysis and selection of optimal pulse parameters. We used the variable nutation angle (VNA) method to determine T-1's of 5FU and FNuc in subcutaneous Walker 25 rat mammary carcinosarcoma tumors transfected with a cytosine deaminase/uracil phosphoribosyltransferase fusion gene. We calibrated in vivo NAs using methoxydifluoroacetate to ensure the accuracy of these measurements. The T-1's were calculated based on signal intensities acquired with NAs of 20degrees, 35degrees, 45degrees, 60degrees, and 75degrees. The acquisition order of these NAs was shuffled to reduce the effect of signal variations. The determined T-1's for 5FU and FNuc (2.3 +/- 0.1 s and 1.3 +/- 0.1 s, respectively) represent the first reported in vivo measurements for these metabolites in tumor.