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Noninvasive molecular imaging of MYC mRNA expression in human breast cancer xenografts with a [99mTc]peptide-peptide nucleic acid-peptide chimera.
- Source :
-
Bioconjugate chemistry [Bioconjug Chem] 2005 Jan-Feb; Vol. 16 (1), pp. 70-9. - Publication Year :
- 2005
-
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.
- Subjects :
- Animals
Breast Neoplasms metabolism
Chimera
Disease Models, Animal
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
Neoplasm Transplantation
Proto-Oncogene Proteins c-myc genetics
RNA, Messenger metabolism
Radiography
Receptor, IGF Type 1 metabolism
Time Factors
Tissue Distribution
Tumor Cells, Cultured
Breast Neoplasms diagnostic imaging
Diagnostic Imaging
Peptide Nucleic Acids
Proto-Oncogene Proteins c-myc metabolism
RNA, Messenger analysis
Technetium Tc 99m Sestamibi
Xenograft Model Antitumor Assays
Subjects
Details
- Language :
- English
- ISSN :
- 1043-1802
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Bioconjugate chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15656577
- Full Text :
- https://doi.org/10.1021/bc0497923