Vascular proteomic mapping in vivo

Abstract

Molecular targeting of drugs and imaging agents remain important yet elusive goals in modern medicine. Technological advancements in genomics and proteomics methods have detected differentially expressed genes and proteins, uncovering many new candidate targets in a wide array of diseases and tissues. However, methods to validate potential targets in vivo tend to be quite laborious so that the validation and testing phase has become rate-limiting in bringing treatments to the clinic. There is a critical need for integrated approaches combining state-of-the-art methodologies in proteomics and in vivo imaging to accelerate validation of newly discovered vascular targets for nanomedicines, drugs, imaging agents, and gene vectors. This paper is a review of vascular targeting and proteomics, and will present recent developments in proteomic imaging. A new in vivo organellar proteomic imaging platform will be discussed, which combines subcellular fractionation, mass spectrometry, bioinformatic database interrogation, monoclonal antibody technology and a battery of imaging modalities to rapidly discover and validate tissue-specific endothelial protein targets in vivo. Technological advancements are permitting large-scale proteomic mapping to be performed. New targets have been discovered that permit organ-specific targeting in vivo. Improvements in imaging are creating standards for validation of targets in vivo. Tumor imaging and radioimmunotherapy have also been improved through these efforts. Although we are moving towards a comprehensive mapping of the protein expression by the endothelium, much more needs to be done.