In vivo uptake of carbon-14-colchicine for identification of tumor multidrug resistance.

UNLABELLED: A major limitation in the treatment of cancer with natural product chemotherapeutic agents is the development of multidrug resistance (MDR). Multidrug resistance is attributed to enhanced expression of the multidrug resistance gene MDR1. Colchicine (CHC) is known to be one of the MDR drugs. We have previously demonstrated that it is possible to distinguish multidrug-resistant tumors from multidrug-sensitive tumors in vivo on the basis of tritium (3H) uptake following injection of 3H-CHC. METHODS: The present studies were carried out in xenografted animals using 14C-CHC which may be more indicative of 11C-labeled CHC distribution with regard to circulating metabolites, since metabolic processes following injection of (ring C, methoxy-11C)-CHC may produce significant amounts of circulating 1-carbon fragments (i.e., methanol and/or formaldehyde). Experiments were carried out at a dose of 2 mg/kg. RESULTS: Activity concentration per injected dose was approximately twice as great in sensitive as in resistant tumors (p < 0.05) at 60 min following intravenous injection of 14C-CHS. About 75% of total activity was CHC in the sensitive tumors. The findings are further confirmed by the quantitative autoradiographic evaluation of resistant and sensitive tumors. CONCLUSIONS: These studies confirm our previous observations that it is possible to noninvasively distinguish multidrug-resistant tumors from sensitive tumors in vivo based on uptake of an injected MDR drug using a 14C-labeled CHC at the same position and of comparable specific activity to a 11C-CHC tracer used for PET imaging.