Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT

Abstract

Objectives: F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose of F-HX4 using whole-body PET/computed tomography (CT) scans in monkeys and humans.

Methods: Successive whole-body PET/CT scans were done after the injection of F-HX4 in four healthy humans (422±142 MBq) and in three rhesus monkeys (189±3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software.

Results: The bladder, liver, and kidneys showed the highest percentage of the injected radioactivity for humans and monkeys. For humans, approximately 45% of the activity is eliminated by bladder voiding in 3.6 h, and for monkeys 60% is in the bladder content after 3 h. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415±18 (monkeys) and 299±38 μGy/MBq (humans), in the 4.8-h bladder voiding interval model. The average value of effective dose for the adult male was estimated at 42±4.2 μSv/MBq from monkey data and 27±2 μSv/MBq from human data.

Conclusion: Bladder, kidneys, and liver have the highest uptake of injected F-HX4 activity for both monkeys and humans. The urinary bladder wall receives the highest dose of F-HX4 and is the critical organ. Thus, patients should be encouraged to maintain adequate hydration and void frequently. The effective dose of F-HX4 is comparable with that of other F-based imaging agents.

Trial registration: ClinicalTrials.gov NCT00606424.

Figures

Fig. 1

Synthesis of 18F-HX4 from Precursor

Fig. 2

Decay-corrected anterior maximum-intensity projections of PET at 17, 82, 120, 156, and 199 min (from left to right) after injection of 18F-HX4 in a female volunteer. There is rapid clearance of activity in kidneys, liver and bladder. Gallbladder activity peaks at 82 min then decreases with time

Fig. 3

Mean percentage of injected activity and standard deviation (SD) for top 3 organs determined on the basis of 4 18F-HX4 PET emission scans in human volunteers, as a function of time after injection. Rapid clearance of activity is observed in the organs

Fig. 4

Decay-corrected anterior maximum-intensity projections of PET at 3, 13, 40, 77 and 187 min (from left to right) after injection of 18F-HX4 in a rhesus monkey. The liver and kidney activities decrease rapidly with time, and bladder accumulates activity with time (there is no voiding of bladder as the monkey is anesthetized)

Fig. 5

Mean percentage of injected activity and standard deviation (SD) for top three organs determined on the basis of three rhesus monkey 18F-HX4 PET emission scans, as a function of time after injection. Liver and kidney activities decrease rapidly with time, and bladder activity increases with time (there is no voiding as monkeys are anesthetized)