Imperial College London
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ProfessorPatriciaPrice

Faculty of Medicine, Department of Surgery & Cancer

Visiting Professor
 
 
 
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Contact

 

p.price

 
 
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Location

 

BN1/24 B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Saleem:2000,
author = {Saleem, A and Yap, J and Osman, S and Brady, F and Suttle, B and Lucas, SV and Jones, T and Price, PM and Aboagye, EO},
journal = {Lancet},
pages = {2125--2131},
title = {Modulation of fluorouracil tissue pharmacokinetics by eniluracil: in-vivo imaging of drug action},
url = {http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T1B-40R4BY6-1C-9&_cdi=4886&_orig=search&_coverDate=06%2F17%2F2000&_qd=1&_sk=996440778&view=c&wchp=dGLbVtz-lSzBA&_acct=C000024058&_version=1&_userid=494590&md5=1da2e3ade9934a59fce9212fdb16c0a7&ie=f.pdf},
volume = {355},
year = {2000}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Fluorouracil is widely used for chemotherapy of gastrointestinal cancer, but response rates are poor. Eniluracil is being developed as an inactivator of dihydropyrimidine dehydrogenase, the enzyme that brings about first-pass degradation of fluorouracil. We studied the mechanism of action of eniluracil by measuring with positron emission tomography (PET) the effect of eniluracil on tumour and normal-tissue pharmacokinetics of fluorine-18-labelled fluorouracil. METHODS: Six patients with advanced gastrointestinal cancers were studied. PET scanning was done after injection of oxygen-15-labelled water to assess tissue blood flow, followed by 1 mg/m2 18F-fluorouracil. We compared the pharmacokinetics of 18F-fluorouracil when the patients had not received eniluracil, during a 4-day course of oral eniluracil, and during a 28-day course of oral fluorouracil plus eniluracil. FINDINGS: In eniluracil-naive patients, 18F-fluorouracil localised more strongly (mean 0.0234% [SE 0.0019] of injected activity per mL tissue at 11 min) in liver than in tumours (0.0032% [0.0004]). There was substantial inhibition, after eniluracil administration, of radiotracer uptake and retention in normal liver (mean area under the time versus radioactivity curve 0.927 [SE 0.086] vs 1.857 [0.169] m2 mL(-1) s) and kidneys (1.096 [0.048] vs 5.043 [0.915] m2 mL(-1) s). There was also an increase in plasma uracil and unmetabolised 18F-fluorouracil and an increase in the radiotracer half-life in tumours (2.3 h to >4.0 h). INTERPRETATION: Two events strongly suggested increased exposure of 18F-fluorouracil and its anabolites in the tumours, consistent with the inactivation of dihydropyrimidine dehydrogenase: a selective decrease in radiotracer exposure in normal liver and kidneys compared with tumours; and an increase in radiotracer half-life in tumours.
AU  - Saleem,A
AU  - Yap,J
AU  - Osman,S
AU  - Brady,F
AU  - Suttle,B
AU  - Lucas,SV
AU  - Jones,T
AU  - Price,PM
AU  - Aboagye,EO
EP  - 2131
PY  - 2000///
SP  - 2125
TI  - Modulation of fluorouracil tissue pharmacokinetics by eniluracil: in-vivo imaging of drug action
T2  - Lancet
VL  - 355
ER  -
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