Metabolites of 2'-fluoro-2'-deoxy-D-glucose detected by 19F magnetic resonance spectroscopy in vivo predict response of murine RIF-1 tumors to 5-fluorouracil.
There is a clinical need for early detection of tumor response to therapy. This study aimed to determine whether metabolites of fluorodeoxyglucose (FDG) detected in solid mouse tumors in situ by I9F magnetic resonance spectroscopy (19F MRS) correlated with response to 5-fluorouracil chemotherapy. After injection of FDG (1.4 mmol/kg i.p.), uptake and metabolism was monitored for 2 h in RIF-1 tumors. FDG was detectable immediately, and after 10 min, a second broad peak was detected 5-6 ppm upfield. 19F MRS analysis of cell and tumor extracts in vitro showed that the upfield peak (> or =15% of the total detectable 19F signal) consisted of the epimer alpha-fluorodeoxymannose (FDM) and various conjugates. Mice treated with 5-fluorouracil (130 mg/kg) received, 48 h later, a repeat dose of FDG. The change in the rate of FDM formation, but not the FDG or total 19F signal, correlated significantly with the response to 5-fluorouracil (P = 0.032), suggesting that 19F MRS of FDM metabolism in vivo may be a novel means of predicting tumor response.
McSheehy
P M
PM
Department of Biochemistry and Immunology, St George's Hospital Medical School, London, United Kingdom.
Leach
M O
MO
Judson
I R
IR
Griffiths
J R
JR
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D002457:Cell Extracts; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007536:Isomerism; D007554:Isotopes; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D012210:Rhamnose / Q000031:analogs & derivatives / Q000378:metabolism; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D002457:Cell Extracts; D007554:Isotopes; D019788:Fluorodeoxyglucose F18; C017190:2-deoxy-2-fluoromannose; D006593:Hexokinase; D005956:Glucose-6-Phosphate Isomerase; D012210:Rhamnose; D005472:Fluorouracil