Human biodistribution and radiation dosimetry of the tachykinin NK ₁ antagonist radioligand [18F]SPA-RQ: Comparison of thin-slice, bisected, and 2-dimensional planar image analysis

¹⁸F-Labeled substance P antagonist-receptor quantifier ([ ¹⁸F]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 NK₁ receptors with PET. The aims of this study were to estimate the radiation safety profile and relative risks of [₁₈F]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) [¹⁸F]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 μSv/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.