Targeting ELTD1, an angiogenesis marker for glioblastoma (GBM), also affects VEGFR2: molecular-targeted MRI assessment

American Journal of Nuclear Medicine and Molecular Imaging

Jadith Ziegler¹  Michelle Zalles²  Nataliya Smith³  Jonathan D Wren⁴  Debra Saunders⁵  Megan Lerner⁶  Maulin Patel⁷  Kar-Ming Fung⁸ 

[1] Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma, OK, USA;Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma, OK, USA;Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma, OK, USA;Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA;Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA;Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA;Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA;Surgery Research Laboratory, University of Oklahoma Health Sciences Center, Oklahoma, OK, USA

关键词: Glioblastoma (GBM);    ELTD1;    VEGFR2;    orthotopic G55 xenograft glioma model;    in vivo;    MRI;    rCBF;    molecular-targeted MRI (mt-MRI);   

DOI  :  

学科分类：过敏症与临床免疫学

来源: e-Century Publishing Corporation

【 摘 要 】

Glioblastomas (GBM) are deadly brain tumors that currently do not have long-term patient treatments available. GBM overexpress the angiogenesis factor VEGF and its receptor VEGFR2. ETLD1 (epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1), a G-protein coupled receptor (GPCR) protein, we discovered as a biomarker for high-grade gliomas, is also a novel regulator of angiogenesis. Since it was established that VEGF regulates ELTD1, we wanted to establish if VEGFR2 is also associated with ELTD1, by targeted antibody inhibition. G55 glioma-bearing mice were treated with either anti-ELTD1 or anti-VEGFR2 antibodies. With the use of MRI molecular imaging probes, we were able to detect in vivo levels of either ELTD1 (anti-ELTD1 probe) or VEGFR2 (anti-VEGFR2 probe). Protein expressions were obtained for ELTD1, VEGF or VEGFR2 via immunohistochemistry (IHC). VEGFR2 levels were significantly decreased (P < 0.05) with anti-ELTD1 antibody treatment, and ELTD1 levels were significantly decreased (P < 0.05) with anti-VEGFR2 antibody treatment, both compared to untreated tumors. IHC from mouse tumor tissues established that VEGFR2 and ELTD1 were co-localized. The mouse anti-ELTD1 antibody treatment study indicated that anti-VEGFR2 antibody treatment does not significantly increase survival, decrease tumor volumes, or alter tumor perfusion (measured as relative cerebral blood flow or rCBF). Conversely, anti-ELTD1 antibody treatment was able to significantly increase animal survival (P < 0.01), decrease tumor volumes (P < 0.05), and reduce change in rCBF (P < 0.001), when compared to untreated or IgG-treated tumor bearing mice. Anti-ELTD1 antibody therapy could be beneficial in targeting ELTD1, as well as simultaneously affecting VEGFR2, as a possible GBM treatment.

【 授权许可】

CC BY-NC