99mTc-peptide-peptide nucleic acid probes for imaging oncogene mRNAs in tumours
| Autor: | Wenyi Qin, Xiaobing Tian, Wickstrom E, Mohan R. Aruva, P. S. Rao, Edward R. Sauter, Mathew L. Thakur |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Peptide Nucleic Acids
Metabolic Clearance Rate Mice Nude Breast Neoplasms Peptide Pentapeptide repeat Proto-Oncogene Proteins c-myc Mice Chimera (genetics) chemistry.chemical_compound Gene expression Biomarkers Tumor Animals Humans Tissue Distribution Radiology Nuclear Medicine and imaging RNA Messenger Radionuclide Imaging Polymerase chemistry.chemical_classification Peptide nucleic acid biology Oligonucleotide General Medicine Molecular biology Reverse transcriptase Technetium Compounds chemistry Organ Specificity Isotope Labeling biology.protein Radiopharmaceuticals |
| Zdroj: | Nuclear Medicine Communications. 24:857-863 |
| ISSN: | 0143-3636 |
| DOI: | 10.1097/01.mnm.0000084583.29433.df |
| Popis: | 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 99m Tc 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 99 m Tc and their tissue distribution was examined in athymic nude mice bearing experimental human breast tumours. 99m Tc 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 99m Tc-peptide-PNA probes might be useful for imaging gene expression in tumours, and the approach is worthy of further investigation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|