An innovative approach for the synthesis of dual modality peptide imaging probes based on the native chemical ligation approach

The synthesis of a dual peptide-based imaging probe consists of two steps performed in aqueous solution under mild conditions.

Identification, Characterization, and Optimization of Integrin αvβ6-Targeting Peptides from a One-Bead One-Compound (OBOC) Library: Towards the Development of Positron Emission Tomography (PET) Imaging Agents

The current translation of peptides identified through the one-bead one-compound (OBOC) technology into positron emission tomography (PET) imaging agents is a slow process, with a major delay between ligand identification and subsequent lead optimization. This work aims to streamline the development process of 18F-peptide based PET imaging agents to target the integrin αvβ6. By directly identify αvβ6–targeting peptides from a 9-mer 4-fluorobenzoyl peptide library using the on-bead two-color (OBTC) cell-screening assay, a total of 185 peptide beads were identified and 5 beads sequenced for further evaluation. The lead peptide 1 (VGDLTYLKK(FB), IC50 = 0.45 ± 0.06 μM, 25% stable in serum at 1 h) was further modified at the N-, C-, and bi-termini. C-terminal PEGylation increased the metabolic stability (>95% stable), but decreased binding affinity (IC50 = 3.7 ± 1 μM) was noted. C-terminal extension (1i, VGDLTYLKK(FB)KVART) significantly increased binding affinity for integrin αvβ6 (IC50 = 0.021 ± 0.002 μM), binding selectivity for αvβ6-expressing cells (3.1 ± 0.8:1), and the serum stability (>99% stable). Our results demonstrate the challenges in optimizing OBOC-derived peptides, indicate both termini of 1 are sensitive to modifications, and show that further modification of 1 is necessary to demonstrate utility as an 18F-peptide imaging agent.

Fluorine-18 capture by substituted BODIPY derivatives

For the medical community to effectively decrease the number of deaths caused by cancer each year, we must develop tools that allow for the early detection of biological abnormalities. Earlier detection is key to increasing the survival rate among cancer patients. A major tool currently used by the medical community is molecular imaging. However, the scope of molecular imaging is limited, so new molecular imaging agents must be developed. One the most ubiquitous biological molecules are peptides, and changes in peptide expression has been associated with cancer. However, molecular imaging does not presently have the tools required to monitor the entire class of peptides. In order to increase the scope of molecular imaging in regard to peptides, we have endeavored to create a new class of peptide imaging agents based on the BODIPY fluorophore. To date, we have demonstrated the ability of this scaffold to work effectively as an imaging agent in mouse models. These dyes are lipophilic in vivo so newer generations of this scaffold will have to address these concerns.