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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Nuclear Medicine & PET Research, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. aam.vanderveldt@vumc.nl
Astrid A M
AA
van der Veldt
N Harry
NH
Hendrikse
Egbert F
EF
Smit
Martien P J
MP
Mooijer
Anneloes Y
AY
Rijnders
Winald R
WR
Gerritsen
Jacobus J M
JJ
van der Hoeven
Albert D
AD
Windhorst
Adriaan A
AA
Lammertsma
Mark
M
Lubberink
D000368:Aged; D001692:Biological Transport; D002250:Carbon Radioisotopes; D000077143:Docetaxel; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D011874:Radiometry; D043823:Taxoids / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D014057:Tomography, X-Ray Computed
D002250:Carbon Radioisotopes; D043823:Taxoids; D000077143:Docetaxel