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Alkylphosphocholines: influence of structural variation on biodistribution at antineoplastically active concentrations

  • Original Articles
  • Alkylphosphocholines, Methyl-nitroso-urea, mammary tumor, Biodistribution
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Summary

Hexadecylphosphocholine (HPC) and octadecylphosphocholine (OPC) show very potent antitumor activity against autochthonous methylnitrosourea-induced mammary carcinomas in rats. The longer-chain and unsaturated homologue erucylphosphocholine (EPC) forms lamellar structures rather than micelles, but nonetheless exhibits antineoplastic activity. Methylnitrosourea was used in the present study to induce autochthonous mammary carcinomas in virgin Sprague-Dawley rats. At 6 and 11 days following oral therapy, the biodistribution of HPC, OPC and EPC was analyzed in the serum, tumor, liver, kidney, lung, small intestine, brain and spleen of rats by high-performance thin-layer chromatography. In contrast to the almost identical tumor response noted, the distribution of the three homologues differed markedly. The serum levels of 50 nmol/ml obtained for OPC and EPC were much lower than the value of 120 nmol/ml measured for HPC. Nevertheless, the quite different serum levels resulted in similar tumor concentrations of about 200 nmol/g for all three of the compounds. Whereas HPC preferably accumulated in the kidney (1 μmol/g), OPC was found at increased concentrations (400 nmol/g) in the spleen, kidney and lung. In spite of the high daily dose of 120 μmol/kg EPC as compared with 51 μmol/kg HPC or OPC, EPC concentrations (100–200 nmol/g) were low in most tissues. High EPC concentrations were found in the small intestine (628 nmol/g). Values of 170 nmol/g were found for HPC and OPC in the brain, whereas the EPC concentration was 120 nmol/g. Obviously, structural modifications in the alkyl chain strongly influence the distribution pattern of alkylphosphocholines in animals. Since EPC yielded the highest tissue-to-serum concentration ratio in tumor tissue (5.1) and the lowest levels in other organs, we conclude that EPC is the most promising candidate for drug development in cancer therapy.

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Authors and Affiliations

  1. Max-Planck-Institut für biophysikalische Chemie, Am Fassberg, D-3400, Göttingen, Germany

    Jochem Kötting & Hansjörg Eibl

  2. Institut für Toxikologie u. Chemotherapie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-6900, Heidelberg, Germany

    Martin R. Berger

  3. Abt. Hämatologie/Onkologie, Medizinische Universitätsklinik, Robert-Koch-Strasse 40, D-3400, Göttingen, Germany

    Clemens Unger

Authors
  1. Jochem Kötting
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  2. Martin R. Berger
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  3. Clemens Unger
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  4. Hansjörg Eibl
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This work was supported by the Deutsche Forschungsgemeinschaft and by a grant from the Bundesministerium für Forschung und Technologie

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Kötting, J., Berger, M.R., Unger, C. et al. Alkylphosphocholines: influence of structural variation on biodistribution at antineoplastically active concentrations. Cancer Chemother. Pharmacol. 30, 105–112 (1992). https://doi.org/10.1007/BF00686401

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  • DOI: https://doi.org/10.1007/BF00686401

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