The Role of Radiolabeled Peptide-Nucleic Acid Chimeras and Peptides in Imaging Oncogene Expression

Oncogenes such as K-RAS, CCND1, HER2, and c-MYC and tumor suppressor gene p53 are overexpressed in various types of cancer cells in vivo. Oncogene peptic nucleic acid and (PNA) probes were synthesized with an insulin-like growth factor 1 receptor peptide specific for the C terminus and a metal ion chelating peptide on the N terminus. Chimeric probes were purified by HPLC and characterized by matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Mismatch PNA sequences served as controls.

K-RAS PNA chimeras inhibited cell proliferation and K-RAS protein expression of the pancreatic cell line AsPC1. PNA-chimeras were labeled with Tc-99m with 97+1.5% yields and evaluated in athymic nude mice bearing BT474 or MCF7 human breast tumor xenografts. Significantly greater tumor uptake (P <0.05) was seen with Tc-99m-PNA probes than the corresponding mismatch probes. Analogs of vasoactive intestinal peptide (VIP) specific for VPAC-1 oncogene receptor expression were similarly synthesized, purified, and characterized. One analog, TP3982, was labeled with positron emitting Cu-64. Tissue distribution of Cu-64-TP3892 in mice bearing human breast cancer T47D xenografts demonstrated enhanced tumor uptake, which permitted unequivocal delineation of tumors by MOSAIC small animal positron emission tomographic (PET) imaging. The results demonstrate the important role of radiolabeled PNAs and peptides in imaging gene expression, and warrant further evaluation.