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.
Turku PET Centre, University of Turku and Turku University Hospital, P.O. Box 52, 20521, Turku, Finland. jussi.hirvonen@utu.fi
Jussi
J
Hirvonen
Anne
A
Roivainen
Jere
J
Virta
Semi
S
Helin
Kjell
K
Någren
Juha O
JO
Rinne
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