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K18 is an anticancer drug for oral administration comprising about five molecules of melphalan, an alkylating drug, covalently bonded to human immunoglobulin G. This study measured the in vitro antitumour activity of K18, melphalan and immunoglobulin G on human myeloma cells (RPMI-8226) and the in vivo antitumour effects of K18 and melphalan in BALB/c nude mice bearing human lung cancer cells (LC-10). The relative tumour-inhibitory effect, in vitro, was found to be: immunoglobulin G less than K18 less than melphalan. This activity of K18 was about half the theoretical value indicating that melphalan molecules are not released easily from the conjugate. K18 showed strong antitumour activity in vivo which continued after stopping administration. On the other hand, the effects of melphalan did not continue after administration was stopped. The distribution of [125I] K18 and [14C]melphalan was examined in BALB/c nude mice 14 days after implantation of LC-10 cells. Radioactivity levels in the major organs showed a transient rapid increase followed by a gradual decline. In tumours, [14C]melphalan levels increased transiently and then decreased, whereas [125I]K18 levels persisted following intravenous administration.
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