Biodistribution, Dosimetry, and Pharmacokinetics of ⁶⁸Ga-CBP8: A Type I Collagen–Targeted PET Probe

Abstract

The ⁶⁸Ga-Collagen Binding Probe #8, ⁶⁸Ga-CBP8, is a peptide-based, type I collagen–targeted probe developed for imaging of tissue fibrosis. The aim of this study was to determine the biodistribution, dosimetry, and pharmacokinetics of ⁶⁸Ga-CBP8 in healthy human subjects. Methods: Nine healthy volunteers (5 male and 4 female) underwent whole-body ⁶⁸Ga-CBP8 PET/MRI using a Biograph mMR scanner. The subjects were imaged continuously for up to 2 h after injection of ⁶⁸Ga-CBP8. A subset of subjects underwent an additional imaging session 2–3 h after probe injection. OLINDA/EXM software was used to calculate absorbed organ and effective dose estimates based on up to 17 regions of interest (16 for men) defined on T2-weighted MR images and copied to the PET images, assuming a uniform distribution of probe concentration in each region. Serial blood sampling up to 90 min after probe injection was performed to assess blood clearance and metabolic stability. Results: The mean injected activity (±SD) of ⁶⁸Ga-CBP8 was 220 ± 100 MBq (range, 113–434 MBq). No adverse effects related to probe administration were detected. ⁶⁸Ga-CBP8 demonstrated an extracellular distribution with predominantly rapid renal clearance. Doses on the urinary bladder were 0.15 versus 0.19 mGy/MBq for men versus women. The highest absorbed doses for the rest of the organs were measured in the kidneys (0.078 vs. 0.088 mGy/MBq) and the liver (0.032 vs. 0.041 mGy/MBq). The mean effective dose was 0.018 ± 0.0026 mSv/MBq using a 1-h voiding model. The ⁶⁸Ga-CBP8 signal in the blood demonstrated biexponential pharmacokinetics with an initial distribution half-life of 4.9 min (95% CI, 2.4–9.4 min) and a 72-min elimination half-life (95% CI, 47–130 min). The only metabolite observed had a long blood plasma half-life, suggesting protein-bound ⁶⁸Ga. Conclusion: ⁶⁸Ga-CBP8 displays favorable in-human characteristics and dosimetry similar to that of other gallium-based probes. ⁶⁸Ga-CBP8 could therefore be used for noninvasive collagen imaging across a range of human fibrotic diseases.