Receptor-mediated internalization of chelator-PNA-peptide hybridization probes for radioimaging or magnetic resonance imaging of oncogene mRNAs in tumours
| Autor: | Christopher Cardi, Eric Wickstrom, Mohan R. Aruva, Song Lai, Mathew L. Thakur, Kaijun Zhang, A. Chakrabarti, Nariman V. Amirkhanov, Xiaobing Tian |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Peptide Nucleic Acids
media_common.quotation_subject Mice Nude Biochemistry Models Biological chemistry.chemical_compound Mice Nuclear magnetic resonance Cell Line Tumor Neoplasms medicine Animals Humans Tissue Distribution RNA Neoplasm Internalization Radionuclide Imaging Insulin-like growth factor 1 receptor media_common Chelating Agents medicine.diagnostic_test Peptide nucleic acid Oncogene Cancer Nucleic Acid Hybridization Magnetic resonance imaging medicine.disease Molecular biology Magnetic Resonance Imaging chemistry Positron emission tomography Cancer cell Oligonucleotide Probes Neoplasm Transplantation |
| Zdroj: | Biochemical Society transactions. 35(Pt 1) |
| ISSN: | 0300-5127 |
| Popis: | Early external detection of cancer gene activity might enable early treatment of cancer and might reduce cancer mortality. We hypothesized that oncogene mRNA overexpressed at thousands of copies per malignant cell in a zone of transformed cells could be imaged externally by scintigraphic imaging, PET (positron emission tomography) or MRI (magnetic resonance imaging) with PNA (peptide nucleic acid) hybridization probes that include chelators for metal cations and a cyclized peptide analogue of IGF-1 (insulin-like growth factor 1), D(Cys-Ser-Lys-Cys), to mediate internalization by IGF1R (IGF-1 receptor) overexpressed on cancer cells. We observed that human MCF7 breast cancer cells that overexpress IGF1R efficiently internalized fluorescein–chelator–PNA–D(Cys-Ser-Lys-Cys) to the cytoplasm, but not with D(Cys-Ala-Ala-Cys). Scintigraphic imaging of MCF7 xenografts in immunocompromised mice revealed that CCND1 and MYC [99mTc]chelator–PNA–D(Cys-Ser-Lys-Cys) probes yielded xenograft. PET imaging with [64Cu]chelator–PNA–D(Cys-Ser-Lys-Cys) yielded stronger signals. Scintigraphic imaging of human AsPC1 pancreas cancer xenografts with [99mTc]chelator–KRAS PNA–D(Cys-Ser-Lys-Cys) yielded strong xenograft signals. Stronger xenograft image intensities were obtained by PET imaging of [64Cu]chelator–KRAS PNA–D(Cys-Ser-Lys-Cys). MRI required extension of chelator–polydiamidopropanoate dendrimers from the N-termini of the PNA probes to increase the number of contrast paramagnetic gadolinium (III) cations per probe. These results provide a basis for detection of oncogene activity in tissues from outside the body by hybridization with metal–chelator–PNA–peptides that are selectively internalized by cancer cells. |
| Databáze: | OpenAIRE |
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