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:2008:10.1158/1078-0432.CCR-08-1324,
author = {Saleem, A and Price, PM},
doi = {10.1158/1078-0432.CCR-08-1324},
journal = {Clin Cancer Res},
pages = {8184--8190},
title = {Early tumor drug pharmacokinetics is influenced by tumor perfusion but not plasma drug exposure},
url = {http://dx.doi.org/10.1158/1078-0432.CCR-08-1324},
volume = {14},
year = {2008}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - PURPOSE: Pharmacokinetic parameters derived from plasma sampling are used as a surrogate of tumor pharmacokinetics. However, pharmacokinetics-modulating strategies do not always result in increased therapeutic efficacy. Nonsurrogacy of plasma kinetics may be due to tissue-specific factors such as tumor perfusion. EXPERIMENTAL DESIGN: To assess the impact of tumor perfusion and plasma drug exposure on tumor pharmacokinetics, positron emission tomography studies were done with oxygen-15 radiolabeled water in 12 patients, with 6 patients undergoing positron emission tomography studies with carbon-11 radiolabeled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide and the other 6 with fluorine-18 radiolabeled 5-fluorouracil. RESULTS: We found that tumor blood flow (mL blood/mL tissue/minute) was significantly correlated to early tumor radiotracer uptake between 4 and 6 minutes [standard uptake value (SUV)4-6; rho = 0.79; P = 0.002], tumor radiotracer exposure over 10 minutes [area under the time-activity curve (AUC)0-10; predominantly parent drug; rho = 0.86; P < 0.001], and tumor radiotracer exposure over 60 minutes (AUC0-60; predominantly radiolabeled metabolites; rho = 0.80; P = 0.002). Similarly, fractional volume of distribution of radiolabeled water in tumor (Vd) was significantly correlated with SUV4-6 (rho = 0.80; P = 0.002), AUC0-10 (rho = 0.85; P < 0.001), and AUC0-60 (rho = 0.66; P = 0.02). In contrast, no correlation was observed between plasma drug or total radiotracer exposure over 60 minutes and tumor drug uptake or exposure. Tumor blood flow was significantly correlated to Vd (rho = 0.69; P = 0.014), underlying the interdependence of tumor perfusion and Vd. CONCLUSIONS: Tumor perfusion is a key factor that influences tumor drug uptake/exposure. Tumor vasculature-targeting strategies may thus result in improved tumor drug exposure and therefore drug efficacy.
AU  - Saleem,A
AU  - Price,PM
DO  - 10.1158/1078-0432.CCR-08-1324
EP  - 8190
PY  - 2008///
SN  - 1078-0432
SP  - 8184
TI  - Early tumor drug pharmacokinetics is influenced by tumor perfusion but not plasma drug exposure
T2  - Clin Cancer Res
UR  - http://dx.doi.org/10.1158/1078-0432.CCR-08-1324
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19088034
VL  - 14
ER  -
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