In vivo 5-fluorouracil and fluoronucleotide T1 relaxation time measurements using the variable nutation angle method.
19Fluorine NMRS has the potential to enable noninvasive predictions of tumor response to 5-fluorouracil (5FU) therapy based on tumor pharmacokinetics. Knowledge of the T1'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 T1's of 5FU and FNuc in subcutaneous Walker 256 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 T1's were calculated based on signal intensities acquired with NAs of 20 degrees, 35 degrees, 45 degrees, 60 degrees, and 75 degrees. The acquisition order of these NAs was shuffled to reduce the effect of signal variations. The determined T1'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.
Gade
Terence P F
TP
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Spees
William M
WM
Le
H Carl
HC
Zakian
Kristen L
KL
Ponomarev
Vladimir
V
Doubrovin
Michael
M
Gelovani
Juri G
JG
Koutcher
Jason A
JA
D000818:Animals; D005260:Female; D005472:Fluorouracil / Q000378:metabolism*; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D005472:Fluorouracil