Development of peptides for the in vivo detection of M1 and M2 macrophages in the tumor microenvironment

Abstract

The presence of high macrophage infiltration within solid tumors correlates with chemoresistance, metastasis, poor prognosis and shorter survival of patients. Strategies that can identify macrophages within the tumor microenvironment or reeducate these cells towards a proinflammatory phenotype can improve the therapies for cancer management. Macrophages are among the most abundant cells in the tumor microenvironment. They display distinct states of activation and functional plasticity in response to different microenvironmental signals. Tumor associated macrophages are defined as macrophages residing within the tumor microenvironment. They interact with tumor cells and elements from the tumor stroma; and promote many specific features of cancer including, growth, angiogenesis, invasion and metastasis by releasing chemokines, cytokines and proteases that modify the environment. Molecular imaging plays an essential role in diagnosis and treatment of tumor. It enables location of tumours in the body, visualizing the expression and activity of specific molecules and biological processes that can influence tumor behavior and response to therapy. Targeted molecular imaging probes have become indispensable tools in cancer diagnostics based on their ability to non-invasively detect disease in vivo. Recent technological advances have resulted in various strategies for designing probes, including the successful development and application of the peptide-based probes. Peptides represent a class of agents that bind to their target with high affinity. They are relatively easy to synthesize and their smaller size often improves tissue penetration. Furthermore, peptides have good biocompatibility and the vast possibilities for chemical modifications that can be exploited for novel peptide design and improved delivery. The importance of peptides for molecular imaging is elevated due to the overexpression of peptide receptors in many tumors that can be targeted using these biological targeting vectors. The objective of this study is to identify peptides that target M1 and M2 macrophages in tumor tissue and develop and evaluate their use in vitro and in vivo using small animal PET imaging. These imaging agents will potentially aid in the diagnosis of tumor stage and treatment plan, resulting in improved prognosis and increased survival rate.