In vivo studies of fullerene-based materials using endohedral metallofullerene radiotracers

摘要

Biodistribution studies of a water-soluble radioactive metallofullerene compound have been conducted using BALB/c mice. To this end, a sample containing Ho_x@C_(82) (x = 1, 2) was purified and derivatized to prepare the water- soluble metallollillerol, Ho_x@C_(82) (OH)_y.This metallofullerol was then neutron-activated [~(165)Ho[n,#gamma#]~(166)Ho] to prepare the ~(165)Ho_X@C_(82)(OH)_y analog as a radiotracer, which was monitored, after intravenous administration, for up to 48 hours by using dissection radioanalysis, and its biodistribution was compared with a control compound, Na_2[~(166)Ho(DTPA)(H_2O)]. Results showed selective localization of the ~(166)Ho_x@C_(82)(OH)_y tracer in the liver but with slow clearance, as well as uptake by bone without clearance. In contrast, excretion of the control com- pound was nearly quantitative after 1 hour. The fate of ~(166)Ho was also explored by a metabolism study of ~(166)Ho_X@C_(82)(OH)_y in Fischer rats. Results indicated 20 excretion of intact ~(166)Ho_X@C_(82)(OH)_y within 5 days. The present findings demon- strate the feasibility of using water-solubilized metallofullerene radiotracers to monitor the fate of fullerene-based materials in animals, and suggest that water-solubilized fullerene materials, in general, may be useful components in drug design.