Disintegrin-targeted elastin-like polypeptide (ELPs) as a therapeutic and PET diagnostic imaging agent

1733 Objectives Multiple nanocarriers are under investigation as multifunctional agents for packaging, transport and delivery of imaging & therapeutic agents. The polymeric nanocarriers described here are intended to visualize and measure functional characteristics of physiological microenvironments. In this study several elastin-like polypeptide (ELP)-based PET imaging agents were designed and evaluated for their potential use as diagnostic imaging and therapeutic agents for breast cancer. To improve tumor accumulation and bioavailability a neovasculature-targeting protein called vicrostatin (VCN) was appended to ELPs. Methods A series of control ELPs and ELP-VCN fusion proteins was expressed. Biodistribution and microPET imaging studies with ELP alone, VCN and ELP-VCN was performed in mice with MDA-MB-231 tumors at 2, 4, 18 and 48h hours post administration. Image comparison between DOTA labeled and a novel sarcophagine-based chelating agent was also performed. Results Passive accumulation in tumors via the EPR effect (ELP alone) or through specific association of VCN and ELP-VCN with integrins upregulated on the tumor was observed. This association was blocked by prior injection with cold ELP-VCN. The combination of ELP and disintegrin (VCN) seem to prolong intratumoral contrast, resulting in a higher accumulation of the peptide in the tumor when compared to controls. Improved copper-chelation stability with a sarcophagine-based chelator compared to DOTA lead to an improvement in the PET images obtained. Conclusions Increased tumor accumulation with the disintegrin-targeted ELP was observed when compared to ELP or VCN by itself. Further enhancement of PET signal to noise ratio was achieved using a sarcophagine-based chelator