Antitumor and Radiosensitizing Activity of Several Platinum-(+) Dye Complexes

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Abstract
We have prepared several complexes of tetrachloroplatinate with organic molecules bearing diffuse positive charges. A human squamous carcinoma cell line, SCC-25/CP, which is 30-, 10-, and 9-fold resistant to CDDP, carboplatin, and iproplatin, respectively, is as sensitive to the platinum-(+) dye complexes as is the parent SCC-25 cell line. A dose of each platinum-(+) dye complex which produced 50-90% cell kill was selected to assess the radiation sensitizing potential of these agents in vitro. All of the platinum-(+) dye complexes were effective sensitizers of hypoxic cells. Pt(Rh-123)2 (100 .mu.M) produced DMFs of 2.7 and 2.6 in the SCC-25 and SCC-25/CP cells, Pt027 (100 .mu.M) gave DMFs of 2.2 and 2.6 in the SCC-25 and SCC-25/CP cells; PtSA (10 .mu.M) produced DMFs of 2.2 and 2.0 in the SCC-25 and SCC-25/CP cells; and PtDeca (50 .mu.M) gave DMFs of 1.8 and 1.9 in the SCC-25 and SCC-25/CP cells. The antitumor activity of the platinum-(+) dye complexes was assessed in four transplantable mouse tumors and compared with the activity of CDDP. In both intraperitoneal and subcutaneous tumors the platinum-(+) dye complexes had activity comparable to CDDP. In the Lewis lung tumor, increasing doses of Pt(Rh-123)2 produced increasing dose modification when the drug was administered prior to single doses of radiation. A dose of 50 mg/kg of Pt(Rh-123)2, Pt027, or PtDeca produced very similar dose modification in this tumor. Overall, the platinum-(+) dye complexes are effective radiosensitizers both in vitro and in vivo.