The distribution and action of a radioactive oxazine dye in tumor-bearing mice.

of cancer with the hope of developing useful diag nostic and therapeutics agents. The aim in such investigations has been to find a dye which, in the intact animal, stains living tumor cells without staining surrounding tissue. A large number of acid dyes, especially in the azo series, has been rather intensively investigated for such a purpose. From these investigations there has resulted gen eral agreement (1, 11) that acid dyes do not local ize in viable tumor cells but accumulate in the stroma of the tumor The incorporation of a radioactive isotope into a dye molecule has been achieved with several acid dyes (5, 10). Studies of the distribution of radio and intense staining of viable tumor cells when ad ministered orally or parenterally. The halogen de rivatives of Nile blue @Bwere prepared (8) and found to give good staining of tumor cells in mice. The radioactive iodine derivative of Nile blue @B has been prepared (9). In the present work, this radioactive dye has been administered to animals. It is the intent of this paper to describe these cx periments and their results. MATERIALS AND METHODS Radioactive Dye.†" Thedye used is a radioactive iodine derivative of Nile blue @B. The iodine is organically bound and is not in an ionizable state. The structure and nomenclature of the dye are: (C2H5) @ HCH2<>P31 bromo derivatives of trypan blue and Evans blue (5) and of a radioiodo derivative of trypan blue (10) in tumor-bearing mice have been reported. Radioactive diiodofluorescein (6) has been used for the localization of intracranial neoplasms. No results of any direct evaluation of therapeutic ac tivity of these substances have been reported. It has been shown (3, 4) that a basic oxazine dye, Nile blue A (Colour Index number 913), when administered orally to tumor-bearing mice causes diffuse staining of viable tumor cells without stain ing of the tumor stroma or the surrounding tissues. This staining action is accompanied by a marked retardation of the rate of growth of the tumor. Other closely related oxazine dyes were similarly tested. Of these tested, Nile blue @B(Colour In dex number 914) was found to give most uniform 5-(p-radioiodobenzylamino)-9-diethylaminobenzo [a]phenoxazine The preparation of this radioactive dye has been described in detail in a previous publication (9). The specific activity of the dye at the start of this investigation was 0.55 millicurie per gram. For in jection purposes, an …