Evaluation of [11C]MPC-6827 as a microtubule targeting PET radiotracer in cancer lines
Evaluation of [11C]MPC-6827 in cancer
Microtubule (MTs) are implicated in the pathogenesis of cancer, and MT disruption with microtubule-targeted agents (MTA) is a valuable chemotherapeutic strategy. However, most MTAs developed to date are substrates for P-glycoprotein (p-GP) and multidrug resistance protein 1 (MDR1), preventing their use in the treatment of brain malignancies or as in vivo PET imaging agents in the brain. [11C]MPC-6827 is the first brain-penetrating MTA based radiotracer, exhibits excellent uptake and specific binding in rodent brain. The objective of this study is to evaluate the uptake of [11C]MPC-6827 in cell lines of prostate, brain and breast malignancies. [11C]MPC-6827 provided the highest binding in breast cancer cell, MDA-MB-231, among all the cells studied, with 95% specific binding. [11C]MPC-6827 binds to glioblastoma PDX and U251 cells with ~50% and 40% specific binding, whereas, prostate cancer cell line, PC3 cells showed 40% specific binding. [11C]MPC-6827 also exhibits binding to the taxane and colchicine binding sites of MTs, in MDA-MB-231 cells. These data indicate that [11C]MPC-6827 can be a promising PET radiotracer for preclinical imaging of brain and peripheral cancers.
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