Whole-body distribution and radiation dosimetry of the dopamine transporter radioligand [(11)C]PE2I in healthy volunteers.
BACKGROUND
This study reports on the biodistribution and radiation dosimetry of a cocaine analog, the (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl)nortropane (PE2I), labeled with carbon 11 ([(11)C]PE2I). [(11)C]PE2I is used in positron emission tomography (PET) for examination of the dopamine neuronal transporter (DAT). DAT radioligands are often used to evaluate the progression of Parkinson's disease or the efficiency of neuroprotective therapeutics, and, typically, these studies required several successive PET scans.


METHODS
In three healthy male volunteers, whole-body scans were performed up to 2 h following intravenous injection of 321+/-6 MBq of [(11)C]PE2I. For each subject, regions of interest were defined over all visible organs to generate time-activity curves and calculate the percentage of injected activity. Time-activity data were fitted to a monoexponential model, as an uptake phase followed by a mono-exponential washout, or bi-exponential model to obtain residence times. With the use of the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses.


RESULTS
Blood pressure and ECG findings remained unchanged after radioligand injection. The primary route of clearance was renal. Ten minutes after injection, high activities were observed in the kidneys, urinary-bladder, stomach, liver, salivary glands and brain. The urine bladder wall, stomach and liver received the highest absorbed doses. The average effective dose of [(11)C]PE2I was estimated to be 6.4+/-0.6 microSv/MBq.


CONCLUSIONS
The amount of [(11)C]PE2I required for adequate DAT PET imaging results in an acceptable effective dose equivalent permitting two or three repeated cerebral PET studies, with the injection of 222 MBq for each study.
Ribeiro
Maria-João
MJ
Service Hospitalier Frédéric Joliot, Institut d'Imagerie Biomédicale, Direction des Sciences du Vivant, Commissariat à l'Energie Atomique, F-91406 Orsay, France. maria-joao.ribeiro@cea.fr
Ricard
Marcel
M
Lièvre
Marie-Angele
MA
Bourgeois
Sandrine
S
Emond
Patrick
P
Gervais
Philippe
P
Dollé
Frédéric
F
Syrota
André
A
D000328:Adult; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009662:Nortropanes / Q000009:adverse effects / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics*; D012016:Reference Values; D014018:Tissue Distribution
D050483:Dopamine Plasma Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009662:Nortropanes; D019275:Radiopharmaceuticals