%0 Journal Article
%T Targeting ELTD1, an angiogenesis marker for glioblastoma (GBM), also affects VEGFR2: molecular-targeted MRI assessment
%A Debra Saunders
%A Florea Lupu
%A Jadith Ziegler
%A James Battiste
%A Jonathan D Wren
%A Kar-Ming Fung
%A Maulin Patel
%A Megan Lerner
%A Michelle Zalles
%A Nataliya Smith
%A Rheal A Towner
%J Archive of "American Journal of Nuclear Medicine and Molecular Imaging".
%D 2019
%X 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
%K Glioblastoma (GBM)
%K ELTD1
%K VEGFR2
%K orthotopic G55 xenograft glioma model
%K in vivo
%K MRI
%K rCBF
%K molecular-targeted MRI (mt-MRI)
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420708/