Title:2-(ω-Carboxyethyl)pyrrole Antibody as a New Inhibitor of Tumor Angiogenesis and Growth
VOLUME: 17 ISSUE: 6
Author(s):Chunying Wu, Xizhen Wang, Nicholas Tomko, Junqing Zhu, William R. Wang, Jinle Zhu, Bin Wangf, Yanming Wang* and Robert G. Salomon*
Affiliation:Department of Radiology, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, Imaging Center, Weifang Medical University, Weifang, Shandong, 261031, Department of Chemistry, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, Department of Radiology, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, Phillips Academy at Andover, 180 Main Street, Andover, MA 01810, Beachwood High School, Beachwood, OH 44122, Department of Radiology, Bingzhou Medical University, Binzhou, Shandong, 256603, Department of Radiology, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, Chemistry, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106
Keywords:Angiogenesis inhibitors, vascular endothelial growth factor (VEGF), bevacizumab, 2-(ω-carboxyethyl)pyrrole (CEP), positron
emission tomography (PET), and imaging.
Abstract:Background: Angiogenesis is a fundamental process in the progression, invasion, and metastasis of
tumors. Therapeutic drugs such as bevacizumab and ranibuzumab have thus been developed to inhibit vascular
endothelial growth factor (VEFG)-promoted angiogenesis. While these anti-angiogenic drugs have been
commonly used in the treatment of cancer, patients often develop significant resistance that limits the efficacy of
anti-VEGF therapies to a short period of time. This is in part due to the fact that an independent pathway of
angiogenesis exists, which is mediated by 2-(ω-carboxyethyl)pyrrole (CEP) in a TLR2 receptor-dependent
manner that can compensate for inhibition of the VEGF-mediated pathway.
Aims: In this work, we evaluated a CEP antibody as a new tumor growth inhibitor that blocks CEP-induced
angiogenesis.
Method: We first evaluated the effectiveness of a CEP antibody as a monotherapy to impede tumor growth in
two human tumor xenograft models. We then determined the synergistic effects of bevacizumab and CEP
antibody in a combination therapy, which demonstrated that blocking of the CEP-mediated pathway significantly
enhanced the anti-angiogenic efficacy of bevacizumab in tumor growth inhibition indicating that CEP antibody
is a promising chemotherapeutic drug. To facilitate potential translational studies of CEP-antibody, we also
conducted longitudinal imaging studies and identified that FMISO-PET is a non-invasive imaging tool that can
be used to quantitatively monitor the anti-angiogenic effects of CEP-antibody in the clinical setting.
Results: That treatment with CEP antibody induces hypoxia in tumor tissue WHICH was indicated by 43% higher
uptake of [18F]FMISO in CEP antibody-treated tumor xenografs than in the control PBS-treated littermates.
