Biodistribution, dosimetry, and pharmacokinetics of 68Ga-CBP8: a type I collagen targeted PET probe Articles uri icon

authors

  • IZQUIERDO GARCÍA, DAVID
  • DÉSOGÈRE, PAULINE
  • LE FUR, MARIANE
  • SHUVAEV, SERGEY
  • ZHOU, IRIS Y.
  • RAMSAY, IAN
  • LANUTI, MICHAEL
  • CATALANO, ONOFRIO
  • CATANA, CIPRIAN
  • CARAVAN, PETER
  • MONTESI, SYDNEY B.

publication date

  • May 2023

start page

  • 775

end page

  • 781

issue

  • 5

volume

  • 64

International Standard Serial Number (ISSN)

  • 0161-5505

Electronic International Standard Serial Number (EISSN)

  • 1535-5667

abstract

  • 68Ga-CBP8 is a peptide-based, type 1 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: 9 healthy volunteers (5 males / 4 females) underwent whole-body 68Ga-CBP8 PET-MRI using a Biograph mMR scanner (Siemens Healthineers, Erlangen, Germany). Subjects were imaged continuously for up to 2 hours after injection of 68Ga-CBP8. A subset of subjects underwent an additional imaging session 2-3 hours after probe injection. OLINDA/EXM v2.2 software was used to calculate absorbed organ and effective dose estimates based on up to 17 regions of interest (16 for males) defined on T2-weighted MR images and copied to the PET images assuming uniform distribution of probe concentration in each region. Serial blood sampling up to 90 minutes post-probe injection was performed to assess blood clearance and metabolic stability. Results: The mean injected activity (± standard deviation) 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 a predominantly rapid renal clearance. Doses on the urinary bladder were (0.15 vs. 0.19 mGy/MBq for males and females respectively). 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-hour voiding model. 68Ga-CBP8 signal in the blood demonstrated biexponential pharmacokinetics with an initial distribution half-life of 4.9 min (95% confidence interval 2.4 – 9.4 min) and a 72 min elimination half-life (47 – 130 min). The only metabolite observed had a long blood plasma half-life suggesting protein-bound Ga-68. Conclusion: 68Ga-CBP8 displays favorable in-human characteristics and similar dosimetry to other gallium-based probes. 68Ga-CBP8 could therefore be utilized for non-invasive collagen imaging across a wide range of human fibrotic diseases.

subjects

  • Biology and Biomedicine
  • Medicine

keywords

  • pet/mri; radiobiology/dosimetry; radiopharmaceuticals; 68ga-cbp8; pet; collagen; dosimetry; fibrosis