Biodistribution and radiation dosimetry of the integrin marker ¹⁸F-RGD-K5 determined from whole-body PET/CT in monkeys and humans

2-((2S,5R,8S,11S)-5-benzyl-8-(4-((2S,3R,4R,5R,6S)-6-((2-(4- (3- ¹⁸F-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4, 5-trihydroxytetrahydro-2H-pyran-2-carboxamido)butyl)-11-(3- guanidinopropyl)-3, 6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan- 2-yl)acetic acid ( ¹⁸F-RGD-K5) has been developed as an αvβ3 integrin marker for PET. The purpose of this study was to determine the biodistribution and estimate the radiation dose from ¹⁸F-RGD-K5 using whole-body PET/CT scans in monkeys and humans. Methods: Successive wholebody PET/CT scans were obtained after intravenous injection of ¹⁸F-RGD-K5 in 3 rhesus monkeys (167 ± 19 MBq) and 4 healthy humans (583 ± 78 MBq). In humans, blood samples were collected between the PET/CT scans, and stability of ¹⁸F-RGDK5 was assessed. Urine was also collected between the scans, to determine the total activity excreted in urine. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on human and monkey biodistributions. Results: ¹⁸F-RGD-K5 was metabolically stable in human blood up to 90 min after injection, and it cleared rapidly from the blood pool, with a 12-min half-time. For both monkeys and humans, increased ¹⁸F-RGD-K5 uptake was observed in the kidneys, bladder, liver, and gallbladder, with mean standardized uptake values at 1 h after injection for humans being approximately 20, 50, 4, and 10, respectively. For human biodistribution data, the calculated effective dose was 31 ± 1 mSv/MBq, and the urinary bladder wall had the highest absorbed dose at 376 ± 19 μGy/MBq using the 4.8-h bladder-voiding model. With the 1-h voiding model, these doses reduced to 15 ± 1 mSv/MBq for the effective dose and 103 ± 4 μGy/MBq for the absorbed dose in the urinary bladder wall. For a typical injected activity of 555 MBq, the effective dose would be 17.2 ± 0.6 mSv for the 4.8-h model, reducing to 8.3 ± 0.4 mSv for the 1-h model. For monkey biodistribution data, the effective dose to humans would be 22.2 ± 2.4 mSv for the 4.8-h model and 12.8 ± 0.2 mSv for the 1-h model. Conclusion: The biodistribution profile of ¹⁸FRGD- K5 in monkeys and humans was similar, with increased uptake in the bladder, liver, and kidneys. There was rapid clearance of ¹⁸F-RGD-K5 through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both whole-body effective dose and bladder dose can be reduced by more frequent voiding. ¹⁸F-RGD-K5 can be used safely for imaging αvβ3 integrin expression in humans.