Anti-PIGF monoclonal antibody Made to order

In response to injury, the myocardium hypertrophies in an attempt to maintain or augment function, which is associated with ventricular remodeling and changes in capillary density. During the compensatory phase of the hypertrophic response, the myocardium maintains output and is characterized by a coordinated neo-angiogenic and fibrotic response that supports cardiomyocyte health and survival. Emerging evidence shows that paracrine-mediated cross talk between cardiac myocytes and nonmyocytes within the heart is critical for cardiac adaptation to stress, including the extent of hypertrophy and angiogenesis. This review discusses recent results indicating that placental growth factor (PGF; also called PlGF), a secreted factor within the vascular endothelial growth factor superfamily, is a pivotal mediator of adaptive cardiac hypertrophy and beneficial angiogenesis through its ability to coordinate the intercellular communication between different cell types in the heart. (Trends Cardiovasc Med 2011;21: 220-224) (C) 2011 Elsevier Inc. All rights reserved.

Purpose: To evaluate 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging ((18)FDG-PET) as a predictive, noninvasive, pharmacodynamic (PD) biomarker of response following administration of a small-molecule insulin-like growth factor-1 receptor and insulin receptor (IGF-1R/IR) inhibitor, OSI-906. Experimental Design: In vitro uptake studies of H-3-2-deoxy glucose following OSI-906 exposure were conducted evaluating correlation of dose with inhibition of IGF-1R/IR as well as markers of downstream pathways and glucose metabolism. Similarly, in vivo PD effects were evaluated in human tumor cell line xenografts propagated in athymic nude mice by (18)FDG-PET at 2, 4, and 24 hours following a single treatment of OSI-906 for the correlation of inhibition of receptor targets and downstream markers. Results: Uptake of 3H-2-deoxy glucose and (18)FDG was significantly diminished following OSI-906 exposure in sensitive tumor cells and subcutaneous xenografts (NCI-H292) but not in an insensitive model lacking IGF-1R expression (NCI-H441). Diminished PD (18)FDG-PET, collected immediately following the initial treatment agreed with inhibition of pIGF-1R/pIR, reduced PI3K (phosphoinositide 3-kinase) and MAPK (mitogen activated protein kinase) pathway activity, and predicted tumor growth arrest as measured by high-resolution ultrasound imaging. Conclusion: (18)FDG-PET seems to serve as a rapid, noninvasive PD marker of IGF-1R/IR inhibition following a single dose of OSI-906 and should be explored clinically as a predictive clinical biomarker in patients undergoing IGF-1R/IR-directed cancer therapy. Clin Cancer Res; 17(10); 3332-40. (C) 2011 AACR.