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

David Izquierdo-Garcia, Pauline Désogère, Mariane Le Fur, Sergey Shuvaev, Iris Y Zhou, Ian Ramsay, Michael Lanuti, Onofrio A Catalano, Ciprian Catana, Peter Caravan, Sydney B Montesi, David Izquierdo-Garcia, Pauline Désogère, Mariane Le Fur, Sergey Shuvaev, Iris Y Zhou, Ian Ramsay, Michael Lanuti, Onofrio A Catalano, Ciprian Catana, Peter Caravan, Sydney B Montesi

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.

Keywords: 68Ga-CBP8; PET; collagen; dosimetry; fibrosis.

© 2023 by the Society of Nuclear Medicine and Molecular Imaging.

Figures

Graphical abstract
Graphical abstract
FIGURE 1.
FIGURE 1.
Maximum-intensity-projection coronal images of representative subject (subject 4) showing probe uptake pattern of 68Ga-CBP8 from time of injection up to 3 h after injection across all organs. Note fast clearance of tracer from main organs, mostly through renal excretion, and smaller portion through hepatobiliary system, providing desired low, nonspecific background activity across all organs. p.i. = after injection.
FIGURE 2.
FIGURE 2.
Time–activity curves for selected organs representing %ID per organ across time from injection up to 120 min. Each postinjection curve represents average across subjects, with shaded area representing 95% CI of mean.
FIGURE 3.
FIGURE 3.
(A) Whole-blood clearance of 68Ga-CBP8 in 8 subjects. (B) Blood plasma clearance of intact 68Ga-CBP8 probe and 68Ga-based metabolite observed by high-performance liquid chromatography.

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