Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

See our updated masking policy »

Stanford Health Care

Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors. JCI insight Daldrup-Link, H. E., Mohanty, S., Ansari, C., Lenkov, O., Shaw, A., Ito, K., Hong, S. H., Hoffmann, M., Pisani, L., Boudreau, N., Gambhir, S. S., Coussens, L. M. 2016; 1 (6)

Abstract

Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-ß receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies.

View details for PubMedID 27182558

View details for PubMedCentralID PMC4864003