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 mumol/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 mumol/kg
EPC as compared with 51 mumol/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.