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

Autor:	Izquierdo-Garcia D; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts; dizquierdogarcia@mgh.harvard.edu sbmontesi@partners.org.; Harvard Medical School, Boston, Massachusetts.; Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts.; Bioengineering Department, Universidad Carlos III de Madrid, Spain., Désogère P; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.; Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts., Fur ML; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts., Shuvaev S; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts., Zhou IY; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts., Ramsay I; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts., Lanuti M; Harvard Medical School, Boston, Massachusetts.; Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts; and., Catalano OA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Catana C; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts., Caravan P; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts., Montesi SB; Harvard Medical School, Boston, Massachusetts.; Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, Massachusetts.; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2023 May; Vol. 64 (5), pp. 775-781. Date of Electronic Publication: 2022 Dec 08.
DOI:	10.2967/jnumed.122.264530
Abstrakt:	The 68 Ga-Collagen Binding Probe #8, 68 Ga-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 68 Ga-CBP8 in healthy human subjects. Methods: Nine healthy volunteers (5 male and 4 female) underwent whole-body 68 Ga-CBP8 PET/MRI using a Biograph mMR scanner. The subjects were imaged continuously for up to 2 h after injection of 68 Ga-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 68 Ga-CBP8 was 220 ± 100 MBq (range, 113-434 MBq). No adverse effects related to probe administration were detected. 68 Ga-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 68 Ga-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 68 Ga. Conclusion: 68 Ga-CBP8 displays favorable in-human characteristics and dosimetry similar to that of other gallium-based probes. 68 Ga-CBP8 could therefore be used for noninvasive collagen imaging across a range of human fibrotic diseases. (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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