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PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand ¹¹C-(R)-PK11195 in Children and Adults

¹ Department of Pediatrics, School of Medicine, Wayne State University PET Center, Children's Hospital of Michigan, Detroit Medical Center, Detroit, Michigan; ² Department of Neurology, School of Medicine, Wayne State University PET Center, Children's Hospital of Michigan, Detroit Medical Center, Detroit, Michigan; ³ Department of Radiology, School of Medicine, Wayne State University PET Center, Children's Hospital of Michigan, Detroit Medical Center, Detroit, Michigan; and ⁴ Department of Pharmacology, School of Medicine, Wayne State University PET Center, Children's Hospital of Michigan, Detroit Medical Center, Detroit, Michigan

Correspondence: For correspondence or reprints contact: Ajay Kumar, PET Center, Children's Hospital of Michigan, 3901 Beaubien St., Detroit, MI 48201. E-mail: ajay{at}pet.wayne.edu

The PET tracer ¹¹C-(R)-PK11195 (PK) is an antagonist of the peripheral-type benzodiazepine binding site and allows the noninvasive imaging of microglial activation seen in several neurologic disorders affecting the mature and developing brain. The objective of this study was to derive the biodistribution and in vivo radiation dose estimates of PK in children studied for brain inflammatory conditions and in healthy adults. Methods: Twenty-two children (mean age ± SD, 9.5 ± 4 y; range, 4–17 y; 10 girls) who underwent dynamic PK PET for conditions involving brain inflammation were studied. Seven healthy adults (age, 27.4 ± 7.5 y; range, 22–41 y; 3 women) were evaluated using the same protocol. Normal-organ time–activity curves and residence times were derived and absorbed doses then calculated using the OLINDA software. Two other healthy young adults (1 man, 1 woman) also underwent sequential whole-body PET using a PET/CT scanner to obtain corresponding CT images and PK pharmacokinetics. Results: PK uptake was highest in the gallbladder and urinary bladder, followed by the liver, kidney, bone marrow, salivary gland, and heart wall, with minimal localization in all other organs including normal brain and lungs. PK was excreted through the hepatobiliary and renal systems. The average effective dose equivalent was 11.6 ± 0.6 µSv/MBq (mean ± SD) for young children (age, 4–7 y), 7.7 ± 1.0 µSv/MBq for older children (age, 8–12 y), 5.3 ± 0.5 µSv/MBq for adolescents (age, 13–17 y), and 4.6 ± 2.7 µSv/MBq for adults. The gallbladder wall received the highest radiation dose in children younger than 12 y, whereas the urinary bladder wall received the highest dose in older children and adults. For an administered activity of 17 MBq/kg (0.45 mCi/kg), the effective dose equivalent was about 5 mSv or below for all age groups. Conclusion: At clinically practical administered activities, the radiation dose from ¹¹C-PK11195 in both children and adults is comparable to that from other clinical PET tracers and diagnostic radiopharmaceuticals in routine clinical use.

Key Words: biodistribution • dosimetry • ¹¹C-PK11195 • PET • children

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