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*Robert G. Salomon*
Affiliation:
- Department of Radiology, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106,United States
- Chemistry, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106,United States
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.
