|Table of Contents|

Experimental study of near infrared fluorescent molecular probe Cy5-G3CNGRC targeting tumor angiogenesis imaging

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 24
Page:
4519-4523
Research Field:
Publishing date:

Info

Title:
Experimental study of near infrared fluorescent molecular probe Cy5-G3CNGRC targeting tumor angiogenesis imaging
Author(s):
WANG Jiaoya; LIU Songsong; TAO Min; XIONG Ling; JING Gongwei; HAN Sheng; REN Bingxiu
Department of Nuclear Medicine,the Third Affiliated Hospital of Zunyi Medical University(the First People's Hospital of Zunyi),Guizhou Zunyi 563000,China.
Keywords:
molecular probe; fluorescence imaging; asparaginyl-glycine-arginine (NGR); CD13; angiogenesis
PACS:
R73-3
DOI:
10.3969/j.issn.1672-4992.2023.24.006
Abstract:
Objective:CD13 receptor is an important regulator of tumor angiogenesis,and the amino-sequence of asparaginyl-glycine-arginine (NGR) is a specific ligand of CD13.We prepared Cy5-GGGCNGRC(Cy5-G3CNGRC) in order to provide a new imaging method for studying tumor angiogenesis.Methods:Cy5-G3CNGRC was prepared by activated ester method and purified by HPLC.Immortalized human umbilical vein endothelial cells (HUVEC),human aortic endothelial cells (HAEC),CD13-positive human fibrosarcoma cells (HT-1080) and negative human rectal cancer cells (HT-29) were used to establish cell models in vitro to observe the uptake of Cy5-G3CNGCR.HT-29 and HT-1080 tumor-bearing mouse models were established by intraperitoneal injection of Cy5-G3NGR (200 μg/mouse) and fluorescence imaging was performed at 0.5,1,2 and 4 h,respectively,then the T/NT ratio of tumor (target,T) tissue to muscle (non-target,NT) tissue was calculated,and these data were statisticallyanalyzed.Results:Cytological results indicated that HUVEC,HAEC and HT-1080 had obvious uptake of Cy5-G3CNGRC,while HT-29 had almost no uptake.The maximum T/NT ratio of HT-1080 grafts was significantly higher than that of HT-29 grafts (2.25±0.49 vs 1.05±0.08,P=0.004 7,n=5),and the peak value occurred about 2 hours after injection.Conclusion:Cy5-G3CNGRC showed a good affinity to CD13 both in vivo and in vitro,which has certain application value in tumor neovascularization fluorescence imaging.

References:

［1］ GACCHE RN.Compensatory angiogenesis and tumor refractoriness［J］.Oncogenesis,2015,4(6):e153.
［2］ BICKEL ST,JULIANO JD,NAGY JD.Evolution of proliferation and the angiogenic switch in tumors with high clonal diversity［J］.PloS One,2014,9(4):e91992.
［3］ HAINAUT P,PLYMOTH A.Targeting the hallmarks of cancer:towards a rational approach to next-generation cancer therapy［J］.Curr Opin Oncol,2013,25(1):50-51.
［4］ BHAGWAT SV,LAHDENRANTA J,GIORDANO R,et al.CD13/APN is activated by angiogenic signals and is essential for capillary tube formation［J］.Blood,2001,97(3):652-659.
［5］ TERANISHI J,ISHIGURO H,HOSHINO K,et al.Evaluation of role of angiotensin III and aminopeptidases in prostate cancer cells［J］.Prostate,2008,68(15):1666-1673.
［6］ IKEDA N,NAKAJIMA Y,TOKUHARA T,et al.Clinical significance of aminopeptidase N/CD13 expression in human pancreatic carcinoma［J］.Clin Cancer Res,2003,9(4):1503-1508.
［7］ ARAP W,PASQUALINI R,RUOSLAHTI E.Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model［J］.Science,1998,279(5349):377-380.
［8］ ADRIENN KIS,NO'EMI D'ENES,JUDIT P，et al.In vivo assessment of aminopeptidase N (APN/CD13) specificity of different 68Ga-labelled NGR derivatives using PET/MRI imaging［J］.International Journal of Pharmaceutics,2020,589:119881.
［9］ KESSLER T,BAUMEIER A,BRAND C，et al.Aminopeptidase N (CD13):expression,prognostic impact,and use as therapeutic target for tissue factor induced tumor vascular infarction in soft tissue sarcoma［J］.Transl Oncol,2018,11:1271-1282.
［10］ JASZAI J,SCHMIDT MHH.Trends and challenges in tumor anti-angiogenic Therapies［J］.Cells,2019,8:1102.
［11］ DAVID TONNELET,MD PIERRE BOHN,STEPHANIE BECKER,et al.Angiogenesis imaging study using interim ［18F］ RGD-K5 PET/CT in patients with lymphoma undergoing chemotherapy:preliminaryevidence［J］.EJNMMI,Res,2021,11:37.
［12］ WU T,DING X,SU B,et al.Magnetic resonance imaging of tumor angiogenesis using dual-targetingRGD10-NGR9 ultrasmall superparamagnetic iron oxide nanoparticles［J］.Clin Transl Oncol,2018,20:599-606.
［13］ HUANG Rui,PETER S CONTI,CHEN Kai.In vivo tumor angiogenesis imaging using peptide-based near-infrared fluorescent probes［J］.Methods Mol Biol,2016,1444:73-84.
［14］ BARNIEH FM,LOADMAN PM,FALCONER RA.Is tumour-expressed aminopeptidase N (APN/CD13) structurally and functionally unique［J］.Biochimica et Biophysica Acta(BBA)-Reviews on Cancer,2021,1876(2):188641.
［15］ WULFAENGER J,NIEDLING S,RIEMANN D,et al.Aminopeptidase N (APN)/CD13-dependent CXCR4 downregulation is associated with diminished cell migration,proliferation and invasion［J］.Mol Membr Biol,2008,25:72-82.
［16］ RIEMANN D,KEHLEN A,LANGNER J.CD13-not just a marker in leukemia typing［J］.Immunol Today,1999,20:83-88.
［17］ PEREIRA FE,CRONIN C,GHOSH M,et al.CD13 is essential for inflammatory trafficking and infarct healing following permanent coronary artery occlusion in mice［J］.Cardiovasc Res,2013,100:74-83.
［18］ OOSTENDORP M,DOUMA K,WAGENAAR A,et al.Molecular magnetic resonance imaging of myocardial angiogenesis after acute myocardial infarction［J］.Circulation,2010,121:775-783.
［19］ RANGEL R,SUN Y,GUZMAN-ROJAS L,et al.Impaired angiogenesis in aminopeptidase N-null mice［J］.Proc Natl Acad Sci USA,2007,104:4588-4593.
［20］ DONDOSSOLA E,CORTI A,SIDMAN RL,et al.Bone marrow-derived CD13 cells sustain tumor progression:a potential non-malignant target for anticancer therapy［J］.Oncoimmunology,2014,3:e27716.
［21］ MINA-OSORIO P,WINNICKA B,O'CONOR C,et al.CD13 is a novel mediator of monocytic/endothelial cell adhesion［J］.J Leukoc Biol,2008,84:448-459.
［22］G ESPOSITO,F PIROZZI,PNL LENS,et al.Influence of the position of Gr on fluorescence quenching efficiency of SY［J］.Journal of Functional Materials/Gongneng Cailiao,2023,54(2):2006-2035.
［23］ MOHAMED GHONEIM,CATHERINE A MUSSELMAN.Single-molecule characterization of Cy3.5-Cy5.5 dye pair for FRET studies of nucleic acids and nucleosomes［J］.Journal of Fluorescence,2023,33(2):413-421.

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贵州省基础研究计划（自然科学类）项目（编号：黔科合基础〔2019〕1325号）
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