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

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 metallofullerol, Ho(x)@C(82)(OH)(y). This metallofullerol was then neutron-activated ((165)Ho[n,γ](166)Ho) to prepare the (166)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(2)O)]. 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 compound 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 demonstrate 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.