IN-VIVO UPTAKE OF CARBON-14-COLCHICINE FOR IDENTIFICATION OF TUMOR MULTIDRUG-RESISTANCE

A major limitation in the treatment of cancer with natural product che motherapeutic agents is the development of multidrug resistance (MDR). Multidrug resistance is attributed to enhanced expression of the mult idrug resistance gene MDR1. Colchicine (CHC) is known to be one of the MDR drugs. We have previously demonstrated that it is possible to dis tinguish multidrug-resistant tumors from multidrug-sensitive tumors in vivo on the basis of tritium (H-3) uptake following injection of H-3- CHC. Methods: The present studies were carried out in xenografted anim als using C-14-CHC which may be more indicative of C-11-labeled CHC di stribution with regard to circulating metabolites, since metabolic pro cesses following injection of (ring C, methoxy-C-11)-CHC may produce s ignificant amounts of circulating 1-carbon fragments (i.e., methanol a nd/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 mi n following intravenous injection of C-14-CHC. About 75% of total acti vity was CHC in the sensitive tumors. The findings are further confirm ed by the quantitative autoradiographic evaluation of resistant and se nsitive tumors. Conclusions: These studies confirm our previous observ ations that it is possible to noninvasively distinguish multidrug-resi stant tumors from sensitive tumors in vivo based on uptake of an injec ted MDR drug using a C-14- labeled CHC at the same position and of com parable specific activity to a C-11-CHC tracer used for PET imaging.