PET Imaging of CCND1 mRNA in Human MCF7 Estrogen Receptor–Positive Breast Cancer Xenografts with Oncogene-Specific [64Cu]Chelator-Peptide Nucleic Acid-IGF1 Analog Radiohybridization Probes

Treatment of breast cancer is hampered by a large unmet need for rapid, sensitive, specific staging and stratification of palpable and nonpalpable abnormalities. Mammography and physical examinationmissmany early breast cancers, yet detect many be-nign lesions. Cyclin D1, encoded by CCND1 messenger RNA (mRNA), and insulin-like growth factor 1 receptor (IGF1R) are key regulators of cell proliferation that are overexpressed in most breast cancers. Therefore, we hypothesized that malignant breast masses could be imaged and quantitated externally by PET with a dual-specificity probe that targets both CCND1 mRNA and IGF1R. Methods: We designed a CCND1-specific peptide nucleic acid (PNA) hybridization sequence (CTGGT-GTTCCAT), separated by a C-terminal spacer to a cyclized IGF1 peptide analog (D-Cys-Ser-Lys-Cys), for IGF1R-mediated endocytosis. On the N-terminus we attached a chelator (1,4,7