99mTc-peptide-peptide nucleic acid probes for imaging oncogene mRNAs in tumours

Nucl Med Commun. 2003 Aug;24(8):857-63. doi: 10.1097/01.mnm.0000084583.29433.df.


Imaging oncogene mRNA in tumours would provide a powerful tool for the early detection of occult malignant lesions. The goal was to prepare a chimera consisting of a dodecamer antisense peptide nucleic acid (PNA) specific for c-MYC oncogene overexpressed in human breast cancer cells and a chelating moiety that facilitates quantitative radiolabelling with 99mTc and evaluate it for hybridization and tissue distribution in laboratory animals. The pentapeptide chelator-PNA dodecamer specific for c-MYC mRNA was extended from a solid support by 9-fluorenylmethyloxycarbonyl (Fmoc) coupling. Similarly, a chelator-PNA chimera with four central mismatches was also prepared which served as a control. The chimeras were purified, characterized and evaluated for hybridization to c-MYC mRNA by fluorescent, real-time polymerase chain reaction (RT-PCR). The chimeras were labelled with 99mTc and their tissue distribution was examined in athymic nude mice bearing experimental human breast tumours. 99mTc radiolabelling was quantitative and presented a single peak in reversed phase liquid chromatography. Fluorescent real-time polymerase chain reactions using primer and fluorescent probe sets previously calculated for c-MYC mRNA demonstrated inhibition of reverse transcription by the c-MYC specific chimera as compared to that of the control. Tissue distribution studies of antisense and mismatch chimeras at 4 h and 24 h after administration displayed modest accumulation in the liver, and appreciable levels in tumours. These observations suggest that 99mTc-peptide-PNA probes might be useful for imaging gene expression in tumours, and the approach is worthy of further investigation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / metabolism*
  • Humans
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Mice
  • Mice, Nude
  • Organ Specificity
  • Peptide Nucleic Acids / pharmacokinetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / metabolism
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Technetium Compounds / pharmacokinetics*
  • Tissue Distribution


  • Biomarkers, Tumor
  • Peptide Nucleic Acids
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Radiopharmaceuticals
  • Technetium Compounds