Abstract 5735: Synthesis and characterization of PEG-ylated porphyrins for targeting the epidermal growth factor receptor in colorectal cancer detection

Abstract

According to the National Cancer Institute, an estimated 102,900 (colon) and 39,670 (rectal) new cases were obtained in 2010. An estimated 51,370 people have died from colon and rectal cancers combined. This makes colorectal cancer (CRC) the second leading cause of cancer-related deaths in the United States. Consequently, the development of an in-vivo imaging agent that is selective for CRC has long been needed. Much of the detection for tumorigenesis relies on the efficacy in detecting small tumors. Current agents are not selective and often stain tissue not associated with the cancer cells making it difficult to delineate between viable and tumorigenic entities. This project introduces a novel macrocycle conjugated to polyethylene glycol linker, which we hypothesize will serve as the template for a selective molecule with high fluorescence yields that greatly increases earlier detection. Our targeted remedy is a porphyrin that is conjugated to a peptide with an affinity for the Epidermal Growth Factor Receptor (EGFR). Porphyrins are characteristically aromatically stable, contain trademark absorption bands in the visible and near-IR range, and have fluorescence quantum yields much above the current fluorophores. This makes the macrocycle optimal for confocal laser endomicroscopy (CLE) agent production. Consequently, we use a polyethylene glycol linker in order to increase water solubility, retain low toxicity, and to achieve high fluorescence quantum yields, as well as high conjugation yields. In this research, we were able to produce both precursors to the porphyrin-peptide conjugate, MesoPOR-(mono)-3PEG and MesoPOR-(di)-3PEG. These molecules were synthesized successfully with the use of peptide conjugation mechanisms. Molecular weights were confirmed using Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS). Characterization was performed using 1H Nuclear Magnetic Resonance (1H-NMR) and Ultraviolet-Visible Spectroscopy (UV-Vis) of the intended molecules. The synthesized molecules, MesoPOR-(mono) 3PEG and MesoPOR-(di) 3PEG, will be useful in peptide conjugation that targets EGFR. These peptide ligands will increase selectivity and detect CRC via CLE. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5735. doi:1538-7445.AM2012-5735