Human biodistribution and radiation dosimetry of 11C-(R)-PK11195, the prototypic PET ligand to image inflammation.
OBJECTIVE
The positron emission tomography (PET) radiotracer (11)C-(R)-PK11195 allows the in vivo imaging in humans of the translocator protein 18 kDa (TSPO), previously called peripheral benzodiazepine receptor (PBR), a marker of inflammation. Despite its widespread use, the radiation burden associated with (11)C-(R)-PK11195 in humans is not known. To examine this, we performed dynamic whole-body imaging with PET and (11)C-(R)-PK11195 in healthy humans.


METHODS
Five healthy male volunteers were scanned with PET and (11)C-(R)-PK11195, using a dynamic whole-body imaging protocol. An organ-specific method was used to measure accumulated radioactivity in source organs, and residence times were calculated as areas under the curve of time-activity curves expressed as percentage of injected radioactivity. Residence times were used as input for OLINDA/EXM 1.0 software to model the equivalent organ doses and the effective dose for the 70-kg man.


RESULTS
After intravenous injection of (11)C-(R)-PK11195, radioactivity accumulated in organs rich in TSPO as well as routes of excretion: the hepatobiliary system and the urine. The mean effective dose was 4.8 microSv/MBq according to International Commission on Radiological Protection (ICRP) Publication 60 and 5.1 microSv/MBq according to ICRP Publication 103, and the highest equivalent organ doses were observed in the kidneys (14.0 microSv/MBq), spleen (12.5 microSv/MBq) and small intestine (12.2 microSv/MBq).


CONCLUSIONS
Imaging of TSPO with PET using (11)C-(R)-PK11195 is associated with modest radiation exposure, similar in magnitude to most other (11)C-labelled PET tracers, suggesting feasibility of (11)C-(R)-PK11195 imaging in clinical human studies involving multiple scans in the same subjects per year.
Hirvonen
Jussi
J
Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, 20521, Turku, Finland. jussi.hirvonen@utu.fi
Roivainen
Anne
A
Virta
Jere
J
Helin
Semi
S
Någren
Kjell
K
Rinne
Juha O
JO
D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging*; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008024:Ligands; D008297:Male; D008657:Metabolic Clearance Rate; D049268:Positron-Emission Tomography; D011874:Radiometry; D014018:Tissue Distribution; D055815:Young Adult
C504060:(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; D000577:Amides; D007546:Isoquinolines; D008024:Ligands