Biodistribution and radiation dosimetry of 11C-labelled docetaxel in cancer patients.

Abstract

Docetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter (11)C. Non-invasive measurements of [(11)C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [(11)C]docetaxel in humans. Biodistribution of [(11)C]docetaxel was measured in seven patients (five men and two women) with solid tumours using PET/CT. Venous blood samples were collected to measure activity in blood and plasma. Regions of interest (ROI) for various source organs were defined on PET (high [(11)C]docetaxel uptake) or CT (low [(11)C]docetaxel uptake). ROI data were used to generate time-activity curves and to calculate percentage injected dose and residence times. Radiation absorbed doses were calculated according to the MIRD method using OLINDA/EXM 1.0 software. Gall bladder and liver demonstrated high [(11)C]docetaxel uptake, whilst uptake in brain and normal lung was low. The percentage injected dose at 1 h in the liver was 47 +/- 9%. [(11)C]docetaxel was rapidly cleared from plasma and no radiolabelled metabolites were detected. [(11)C]docetaxel uptake in tumours was moderate and highly variable between tumours. The effective dose of [(11)C]docetaxel was 4.7 microSv/MBq. As uptake in normal lung is low, [(11)C]docetaxel may be a promising tracer for tumours in the thoracic region.