title: Noninvasive molecular imaging of MYC mRNA expression in human breast cancer xenografts with a [99mTc]peptide-peptide nucleic acid-peptide chimera.
abstract: 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 [99mTc]chelator peptide on the N-terminus, could measure levels of MYC mRNA noninvasively in human IGF1R-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 [99mTc]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 [99mTc]PNA probe specific for MYC mRNA, but not with the mismatch control. The [99mTc]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.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Tian
authors.forename: Mohan R
authors.initials: MR
authors.lastname: Aruva
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qin
authors.forename: Weizhu
authors.initials: W
authors.lastname: Zhu
authors.forename: Edward R
authors.initials: ER
authors.lastname: Sauter
authors.forename: Mathew L
authors.initials: ML
authors.lastname: Thakur
authors.forename: Eric
authors.initials: E
authors.lastname: Wickstrom
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D002678:Chimera; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020135:Peptide Nucleic Acids; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis* / Q000378:metabolism; D011859:Radiography; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D017256:Technetium Tc 99m Sestamibi; D013997:Time Factors; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D020135:Peptide Nucleic Acids; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D017256:Technetium Tc 99m Sestamibi; D017526:Receptor, IGF Type 1