Pharmacokinetics of Chlorin e6-Cobalt Bis(Dicarbollide) Conjugate in Balb/c Mice with Engrafted Carcinoma

• Main Authors: Arthur B. Volovetsky, Vladimir S. Sukhov, Irina V. Balalaeva, Varvara V. Dudenkova, Natalia Yu. Shilyagina, Аlexey V. Feofanov, Anastasija V. Efremenko, Mikhail A. Grin, Andrey F. Mironov, Igor B. Sivaev, Vladimir I. Bregadze, Anna V. Maslennikova
• Format: Article
• Language: English
• Published: MDPI AG 2017-11-01
• Series: International Journal of Molecular Sciences
• Subjects: boron neutron capture therapy; fluorescent microscopy; boron content; MS-ICP; simple multichamber model; chlorin e6 derivatives
• Online Access: https://www.mdpi.com/1422-0067/18/12/2556

The necessary precondition for efficient boron neutron capture therapy (BNCT) is control over the content of isotope 10B in the tumor and normal tissues. In the case of boron-containing porphyrins, the fluorescent part of molecule can be used for quantitative assessment of the boron content. Study Objective: We performed a study of the biodistribution of the chlorin e6-Cobalt bis(dicarbollide) conjugate in carcinoma-bearing Balb/c mice using ex vivo fluorescence imaging, and developed a mathematical model describing boron accumulation and release based on the obtained experimental data. Materials and Methods: The study was performed on Balb/c tumor-bearing mice (CT-26 tumor model). A solution of the chlorin e6-Cobalt bis(dicarbollide) conjugate (CCDC) was injected into the blood at a dose of 10 mg/kg of the animal’s weight. Analysis of the fluorescence signal intensity was performed at several time points by spectrofluorimetry in blood and by laser scanning microscopy in muscle, liver, and tumor tissues. The boron content in the same samples was determined by mass spectroscopy with inductively coupled plasma. Results: Analysis of a linear approximation between the fluorescence intensity and boron content in the tissues demonstrated a satisfactory value of approximation reliability with a Spearman’s rank correlation coefficient of r = 0.938, p < 0.01. The dynamics of the boron concentration change in various organs, calculated on the basis of the fluorescence intensity, enabled the development of a model describing the accumulation of the studied compound and its distribution in tissues. The obtained results reveal a high level of correspondence between the model and experimental data.