PT  - JOURNAL ARTICLE
AU  - Xiaobing Tian
AU  - Mohan R. Aruva
AU  - Wenyi Qin
AU  - Weizhu Zhu
AU  - Kevin T. Duffy
AU  - Edward R. Sauter
AU  - Mathew L. Thakur
AU  - Eric Wickstrom
TI  - External Imaging of CCND1 Cancer Gene Activity in Experimental Human Breast Cancer Xenografts with <sup>99m</sup>Tc-Peptide-Peptide Nucleic Acid-Peptide Chimeras
DP  - 2004 Dec 01
TA  - Journal of Nuclear Medicine
PG  - 2070--2082
VI  - 45
IP  - 12
4099  - http://jnm.snmjournals.org/content/45/12/2070.short
4100  - http://jnm.snmjournals.org/content/45/12/2070.full
SO  - J Nucl Med2004 Dec 01; 45
AB  - Detection of a new or recurrent breast cancer lesion relies on physical examination and imaging studies, primarily mammography, followed by histopathologic evaluation of biopsy tissue for morphologic confirmation. Approximately 66%–85% of detected lesions are not malignant. Therefore, biopsies are unnecessary for at least two thirds of patients. Human estrogen receptor-positive breast cancer cells typically display an elevated level of cyclin D1 protein because of the overexpression of CCND1 messenger RNA (mRNA) and an elevated level of insulin-like growth factor 1 (IGF1) receptor (IGF1R) because of the overexpression of IGF1R mRNA. We hypothesized that scintigraphic detection of CCND1 peptide nucleic acid (PNA) hybridization probes with a 99mTc-chelating peptide on the N terminus and an IGF1 peptide loop on the C terminus could detect CCND1 mRNA in human MCF7 breast cancer xenografts in nude mice from outside the body. Methods: We prepared the CCND1 probes as well as mismatched controls by solid-phase synthesis. We used fluorescence microscopy to detect the cellular uptake of fluoresceinyl probes and quantitative reverse transcription-polymerase chain reaction to detect the hybridization of probes to mRNA. We imaged 99mTc-probes in MCF7 xenografts scintigraphically and measured distribution by scintillation counting of dissected tissues. Results: IGF1R-overexpressing MCF7 cells internalized the fluorescein-chelator-CCND1 PNA-IGF1 peptide but not the mismatched control peptide. The chelator-CCND1 PNA-IGF1 peptide but not the control peptide lowered the level of cyclin D1 protein in IGF1R-overexpressing MCF7 xenografts in nude mice after intratumoral injection. IGF1R-overexpressing MCF7 xenografts in nude mice were visualized at 4, 12, and 24 h after tail vein administration of the 99mTc-CCND1 antisense probe but not the control probe. 99mTc-chimeras were distributed normally in the kidneys, liver, tumors, and other tissues. Conclusion: Cancer gene activity can be detected from outside the body by probing with radionuclide-chelator-PNA-peptide chimeras.