Noninvasive Molecular Imaging of MYC mRNA Expression in Human Breast Cancer Xenografts with a [~(99m)Tc]Peptide-Peptide Nucleic Acid-Peptide Chimera

摘要

Human estrogen receptor-positive breast cancer cells typically display elevated levels of Myc protein due to overexpression of MYC mRNA,and elevated insulin-like growth factor 1 receptor(IGF1R)due to overexpression of IGF1R mRNA.We hypothesized that scintigraphic detection of MYC peptide nucleic acid(PNA)probes with an IGF1 peptide loop on the C-terminus,and a [~(99m)Tc]chelator peptide on the N-terminus,could measure levels of MYC mRNA noninvasively in human EGF1R-overexpressing MCF7 breast cancer xenografts in nude mice.We prepared the chelator-MYC PNA-IGF1 peptide,as well as a 4-nt mismatch PNA control,by solid-phase synthesis.We imaged MCF7 xenografts scintigraphically and measured the distribution of [~(99m)Tc] probes by scintillation counting of dissected tissues.MCF7 xenografts in nude mice were visualized at 4 and 24 h after tail vein administration of the [~(99m)Tc]PNA probe specific for MYC mRNA,but not with the mismatch control.The [~(99m)Tc]-probes distributed normally to the kidneys,livers,tumors,and other tissues.Molecular imaging of oncogene mRNAs in solid tumors with radiolabel-PNA-peptide chimeras might provide additional genetic characterization of preinvasive and invasive breast cancers.