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:2001,
author = {Saleem, A and Harte, RJ and Matthews, JC and Osman, S and Brady, F and Luthra, SK and Brown, GD and Bleehen, N and Connors, T and Jones, T and Price, PM and Aboagye, EO},
journal = {J Clin Oncol},
pages = {1421--1429},
title = {Pharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in patients by positron emission tomography},
url = {http://www.jco.org/cgi/reprint/19/5/1421.pdf},
volume = {19},
year = {2001}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - PURPOSE: To evaluate tumor, normal tissue, and plasma pharmacokinetics of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA). The study aimed to determine the pharmacokinetics of carbon-11-labeled DACA ([11C]DACA) and evaluate the effect of pharmacologic doses of DACA on radiotracer kinetics. PATIENTS AND METHODS: [11C]DACA (at 1/1,000 phase I starting dose) was administered to 24 patients with advanced cancer (pre-phase I) or during a phase I trial of DACA in five patients. Positron emission tomography (PET) was performed to assess pharmacokinetics and tumor blood flow. Plasma samples were analyzed for metabolite profile of [11C]DACA. RESULTS: There was rapid systemic clearance of [11C]DACA over 60 minutes (1.57 and 1.46 L x min(-1) x m(-2) in pre-phase I and phase I studies, respectively) with the production of several radiolabeled plasma metabolites. Tumor, brain, myocardium, vertebra, spleen, liver, lung, and kidneys showed appreciable uptake of 11C radioactivity. The area under the time-versus-radioactivity curves (AUC) showed the highest variability in tumors. Of interest to potential toxicity, maximum radiotracer concentrations (Cmax) in brain and vertebra were low (0.67 and 0.54 m(2) x mL(-1), respectively) compared with other tissues. A moderate but significant correlation was observed for tumor blood flow with AUC (r = 0.76; P =.02) and standardized uptake value (SUV) at 55 minutes (r = 0.79; P =.01). A decrease in myocardial AUC ( P =.03) and splenic and myocardial SUV ( P =.01 and.004, respectively) was seen in phase I studies. Significantly higher AUC, SUV, and Cmax were observed in tumors in phase I studies. CONCLUSION: The distribution of [11C]DACA and its radiolabeled metabolites was observed in a variety of tumors and normal tissues. In the presence of unlabeled DACA, pharmacokinetics were altered in myocardium, spleen, and tumors. These data have implications for predicting activity and toxicity of DACA and support the use of PET early in drug
AU  - Saleem,A
AU  - Harte,RJ
AU  - Matthews,JC
AU  - Osman,S
AU  - Brady,F
AU  - Luthra,SK
AU  - Brown,GD
AU  - Bleehen,N
AU  - Connors,T
AU  - Jones,T
AU  - Price,PM
AU  - Aboagye,EO
EP  - 1429
PY  - 2001///
SP  - 1421
TI  - Pharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in patients by positron emission tomography
T2  - J Clin Oncol
UR  - http://www.jco.org/cgi/reprint/19/5/1421.pdf
VL  - 19
ER  -
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