MicroPET imaging of MCF-7 tumors in mice via unr mRNA-targeted peptide nucleic acids

Xiankai Sun, Huafeng Fang, Xiaoxu Li, Raffaella Rossin, Michael J. Welch, John Stephen Taylor

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


As more becomes known about the expression profiles of normal and cancerous cells, it should become possible to design antisense-based imaging agents for the early detection of cancer noninvasively. In this report, we rationally designed and synthesized three antisense and one sense hybrid PNA (peptide nucleic acid) to the unr mRNA that is highly overexpressed in a breast cancer cell line (MCF-7). The conjugates had a four-lysine tail at the carboxy terminus for cell permeation and a DOTA (1,4,7,10-tetraazacyclododecane-N,N′, N″,N‴-tetraacetic acid) chelating moiety at the amino terminal end for chelating 64Cu for biodistribution and microPET imaging studies. Biodistribution of two 64Cu-labeled conjugates with antisense and sense sequences (PNA50 and PNA50S) showed high uptake and long retention in kidney and low uptake and efficient clearance in blood and muscle in normal balb/c mice when administered intravenously or intraperitoneally. Intraperitoneal administration, however, gave a much slower release rate. MCF-7 tumors (100-320 mg) in CB-17 SCID mice were imaged with all four 64Cu-labeled PNA conjugates by microPET, but the image contrast varied with different time points and different conjugates. Of the conjugates studied, 64Cu-DOTA-Y-PNA50-K4 showed the best tumor image quality at all time points with a tumor/muscle ratio of 6.6 ± 1.1 at 24 h postinjection, which is among the highest reported for radiolabeled oligonucleotides. Our work further strengthens the potential of antigene and antisense PNAs to be utilized as specific molecular probes for early detection of cancer and ultimately for patient specific radiotherapy.

Original languageEnglish (US)
Pages (from-to)294-305
Number of pages12
JournalBioconjugate Chemistry
Issue number2
StatePublished - 2005

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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