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.

INTRODUCTION: [(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.

Human biodistribution and radiation dosimetry of the tachykinin NK1 antagonist radioligand [18F]SPA-RQ: comparison of thin-slice, bisected, and 2-dimensional planar image analysis.

UNLABELLED: (18)F-Labeled substance P antagonist-receptor quantifier ([(18)F]SPA-RQ) [2-fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-[(2S,3S)-2-phenyl-piperidin-3-yl)amine] is a selective radioligand for in vivo quantification of tachykinin NK(1) receptors with PET. The aims of this study were to estimate the radiation safety profile and relative risks of [(18)F]SPA-RQ with 3 different methods of image analysis. METHODS: Whole-body PET images were acquired in 7 healthy subjects after injection of 192 +/- 7 MBq (5.2 +/- 0.2 mCi) [(18)F]SPA-RQ. Emission images were serially acquired at multiple time-points from 0 to 120 min and approximately 180-240 min after injection. Urine samples were collected after each imaging session and for 24 h after the last scan to measure excreted radioactivity. Horizontal tomographic images were compressed to varying degrees in the anteroposterior direction to create 3 datasets: thin-slice, bisected, and 2-dimensional (2D) planar images. Regions of interest were drawn around visually identifiable source organs to generate time-activity curves for each dataset. Residence times were determined from these curves, and doses to individual organs and the body as a whole were calculated using OLINDA/EXM 1.0. RESULTS: The lungs, upper large intestine wall, small intestine, urinary bladder wall, kidneys, and thyroid had the highest radiation-absorbed doses. Biexponential fitting of mean bladder and urine activity showed that about 41% of injected activity was excreted via urine. Assuming a 2.4-h urine voiding interval, the calculated effective doses from thin-slice, bisected, and 2D planar images were 29.5, 29.3, and 32.3 microSv/MBq (109, 108, and 120 mrem/mCi), respectively. CONCLUSION: Insofar as effective dose is an accurate measure of radiation risk, all 3 methods of analysis provided quite similar estimates of risk to human subjects. The radiation dose was moderate and would potentially allow subjects to receive multiple PET scans in a single year. Individual organ exposures varied among the 3 methods, especially for structures asymmetrically located in an anterior or posterior position. Bisected and 2D planar images almost always provided higher organ dose estimates than thin-slice images. Thus, either the bisected or 2D planar method of analysis appears acceptable for quantifying human radiation burden, at least for radioligands with a relatively broad distribution in the body and not concentrated in a small number of radiation sensitive organs.