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 (Ho-165[n,gamma]Ho-166) to prepare the Ho-166(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[Ho-166(DTPA) (H2O)]. Results showed selective localization of the Ho-166(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 Ho-166 was also explored by a metabolism study of Ho-166(x)@C-82(OH)(y) in Fischer rats. Results indicated 20% excretion of intact Ho-166(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.