Whole-body biodistribution and radiation dosimetry in monkeys and humans of the phosphodiesterase 4 radioligand [(11)C](R)-rolipram: comparison of two-dimensional planar, bisected and quadrisected image analyses.
BACKGROUND
[(11)C](R)-Rolipram is a selective radioligand for positron emission tomography (PET) imaging of phosphodiesterase 4, an enzyme that metabolizes 3',5'-cyclic adenosine monophosphate. The aim of this study was to estimate the human radiation absorbed dose of the radioligand based on its biodistribution in both monkeys and humans.


METHODS
Whole-body PET images were acquired for 2 h after injecting [(11)C](R)-rolipram in eight healthy humans and three monkeys. The simple method of using a single two-dimensional (2D) planar image was compared to more time-consuming methods that used two (bisected) or four (quadrisected) tomographic images in the anteroposterior direction.


RESULTS
Effective dose was 4.8 microGy/MBq based on 2D planar images. The effective dose was only slightly lower by 1% and 5% using the bisected and quadrisected images, respectively. Nevertheless, the two tomographic methods may have more accurately estimated the exposure of some organs (e.g., kidneys) that are asymmetrically located in the body or have radioactivity that appears to overlap on 2D planar images. Monkeys had a different biodistribution pattern compared to humans (e.g., greater urinary excretion) such that their data overestimated the effective dose in humans by 40%.


CONCLUSIONS
The effective dose of [(11)C](R)-rolipram was modest and comparable to that of other (11)C-labeled radioligands. The simple and far less time-consuming 2D planar method provided accurate and somewhat more conservative estimates of effective dose than the two tomographic methods. Although monkeys are commonly used to estimate human radiation exposures, their data gave a considerable overestimation for this radioligand.
Sprague
David R
DR
Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD 20892-2035, USA.
Fujita
Masahiro
M
Ryu
Yong Hoon
YH
Liow
Jeih-San
JS
Pike
Victor W
VW
Innis
Robert B
RB
D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000032:analysis; D000882:Haplorhini; D006801:Humans; D008657:Metabolic Clearance Rate; D058988:Phosphodiesterase 4 Inhibitors; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000378:metabolism; D020889:Rolipram / Q000378:metabolism*; D014018:Tissue Distribution; D051598:Whole Body Imaging; D014915:Whole-Body Counting
D002250:Carbon Radioisotopes; D058988:Phosphodiesterase 4 Inhibitors; D019275:Radiopharmaceuticals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram