BIODISTRIBUTION OF [CU-64]CU2+ AND VARIANCE OF METALLOTHIONEIN DURINGTUMOR TREATMENT BY COPPER

The kinetic distribution patterns of [Cu-64]Cu2+ in normal mice and in mice bearing tumors (HepA, ascitic tumor) after i.v. injection were s imilar. The i.v. injected [Cu-64]Cu2+ concentrated into mouse liver fi rst and then went to other organs and tissues, such as kidney and tumo r. Most of the [Cu-64]Cu2+ injected concentrated into the liver within 4 h, and about 8% of the total [Cu-64]Cu2+ injected concentrated into the tumor cells at 24 h after i.v. injection, About 80% and 90% of th e soluble [Cu-64]Cu in the livers of tumor-bearing mice and normal mic e, respectively, existed as [Cu-64]CuMT (metallothionein [MT] is a sma ll protein with many cysteine residues) at 4 h after i.v. injection, w hile about 43% of the soluble [Cu-64]Cu2+ in tumor cells combined with MT at 6 h after i.v. injection. After 10 days oral administration of 150 mu g/g body weight copper acetate, the concentration of MT in tumo r cells reduced sharply, from 316 mu g/g tissue to 152 mu g/g tissue, while it increased slightly, from 375 mu g/g tissue to 439 mu g/g tiss ue, in the livers of tumor bearing mice (HepA, solid tumor). The resul ts suggest that MT contributes to the metabolism of copper that is loc alized mainly in the liver after copper administration and that copper can concentrate into mouse tumor cells followed by the reduction of M T in tumor cells. (C) 1998 Elsevier Science Inc.