Human Dosimetry of Carbon-11 Labeled N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide Extrapolated from Whole-body Distribution Kinetics and Radiometabolism in Rats View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-11-26

AUTHORS

Pauliina Luoto, Iina Laitinen, Sami Suilamo, Kjell Någren, Anne Roivainen

ABSTRACT

PurposeCarbon-11 labeled N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide ([11C]PK11195) is a peripheral benzodiazepine receptor (PBR) antagonist that is used as a positron emission tomography (PET) radiopharmaceutical for neuroinflammatory imaging. This study was designed to investigate the radiation dosimetry of [11C]PK11195.ProceduresWhole-body distribution kinetics of intravenously administered [11C]PK11195 in rats was assessed by means of dynamic PET imaging, and estimates for human radiation dosimetry were calculated. Rat plasma and various tissue homogenates obtained at different time points after intravenous injection of [11C]PK11195 were analyzed by reversed-phase gradient radio-HPLC method using online radiodetection. In addition, in vitro stability of [11C]PK11195 was determined in rat brain homogenate by incubation at +37°C.ResultsPET imaging of rats showed the highest radioactivity levels in heart, kidneys, thyroid gland, liver, and lungs. The radioactivity cleared rapidly from lungs and slowly from heart and liver. However, much of the radioactivity retained in kidneys, which was in concordance with the observed low urinary excretion of [11C]PK11195. Extrapolating from the rat data, the effective dose of [11C]PK11195 for a 70-kg man was estimated to be 4.2 ± 0.3 µSv/MBq. Five different radiometabolites were detected in rat plasma, and the level of intact [11C]PK11195 decreased from 80% ± 11% (mean ± SD) at 10 min to 44% ± 5% at 40 min after injection. In rat heart, brain, kidney, and lung homogenates, more than 90% of total radioactivity originated from intact [11C]PK11195. In liver, however, the amount of [11C]PK11195 was approximately 70% and decreased over time, indicating metabolism by liver enzymes.Conclusions[11C]PK11195 showed a fast uptake in many rat tissues and it was metabolized relatively fast in vivo, but not in brain in vitro. The estimated effective dose for humans speaks for the use of [11C]PK11195 in human PET imaging. More... »

PAGES

435-442

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-009-0293-1

DOI

http://dx.doi.org/10.1007/s11307-009-0293-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040145537

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19941083


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