The increased uptake of native serum albumin in tumors is well described. In previous approaches to use this distribution pattern for tumor therapy, albumin molecules were loaded with maximum quantities of antineoplastic drugs. To preserve the properties of native albumin and to avoid enhanced phagocytotic clearance, we used methotrexate (MTX)-albumin-conjugates with a molar loading ratio of 1:1. In this study we evaluated the effects of single injections of MTX-rat-serum albumin (MTX-RSA) containing 50, 20 and 10 mug MTX on 40 BDIX rats bearing O-342 ovarian carcinoma. Tumor volume post treatment and area-under-the-curve of tumor volumes over treatment were compared with an untreated group using the Mann-Whitney U-test. MTX-RSA treatment caused dose dependent effects and in the 50 mug MTX-dosage significant (P 0.01) growth delay. Additional distribution studies with indirectly radio-iodinated MTX-RSA confirmed the prominent tumor uptake of this compound. We conclude that MTX-albumin-conjugates created with optimized labeling techniques and loading ratios cause significant effects even with very low MTX-doses. Thus these compounds may contribute to enhance the efficacy of MTX-treatment.

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