Back to Browse Journals » International Journal of Nanomedicine » Volume 5

Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes

Authors Alessandro Ruggiero, Carlos H Villa, Jason P Holland, et al

Published Date September 2010 Volume 2010:5 Pages 783—802

DOI http://dx.doi.org/10.2147/IJN.S13300

Published 30 September 2010

Alessandro Ruggiero1*, Carlos H Villa1*, Jason P Holland1, Shanna R Sprinkle1, Chad May2, Jason S Lewis1, David A Scheinberg1, Michael R McDevitt1
1Departments of Medicine and Radiology, Pharmacology and Molecular Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, USA; 2ImClone Systems, New York, USA; *Ruggiero and Villa contributed equally to this work

Abstract: Single wall carbon nanotube (SWCNT) constructs were covalently appended with radiometal-ion chelates (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA] or desferrioxamine B [DFO]) and the tumor neovascular-targeting antibody E4G10. The E4G10 antibody specifically targeted the monomeric vascular endothelial-cadherin (VE-cad) epitope expressed in the tumor angiogenic vessels. The construct specific activity and blood compartment clearance kinetics were significantly improved relative to corresponding antibody-alone constructs. We performed targeted radioimmunotherapy with a SWCNT-([225Ac]DOTA)(E4G10) construct directed at the tumor vasculature in a murine xenograft model of human colon adenocarcinoma (LS174T). The specific construct reduced tumor volume and improved median survival relative to controls. We also performed positron emission tomographic (PET) radioimmunoimaging of the tumor vessels with a SWCNT-([89Zr]DFO)(E4G10) construct in the same murine LS174T xenograft model and compared the results to appropriate controls. Dynamic and longitudinal PET imaging of LS174T tumor-bearing mice demonstrated rapid blood clearance (<1 hour) and specific tumor accumulation of the specific construct. Incorporation of the SWCNT scaffold into the construct design permitted us to amplify the specific activity to improve the signal-to-noise ratio without detrimentally impacting the immunoreactivity of the targeting antibody moiety. Furthermore, we were able to exploit the SWCNT pharmacokinetic (PK) profile to favorably alter the blood clearance and provide an advantage for rapid imaging. Near-infrared three-dimensional fluorescent-mediated tomography was used to image the LS174T tumor model, collect antibody-alone PK data, and calculate the number of copies of VE-cad epitope per cell. All of these studies were performed as a single administration of construct and were found to be safe and well tolerated by the murine model. These data have implications that support further imaging and radiotherapy studies using a SWCNT-based platform and focusing on the tumor vessels as the target.

Keywords: actinium-225 (225Ac), zirconium-89 (89Zr), angiogenesis, vascular endothelial-cadherin, radioimmunotherapy (RIT), radioimmunoPET

Download Article [PDF] View Full Text [HTML] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo

Cai L, Wang X, Wang W, Qiu N, Wen J, Duan X, Li X, Chen X, Yang L, Qian Z, Wei Y, Chen L

International Journal of Nanomedicine 2012, 7:4499-4510

Published Date: 14 August 2012

Luminescent single-walled carbon nanotube-sensitized europium nanoprobes for cellular imaging

Avti PK, Sitharaman B

International Journal of Nanomedicine 2012, 7:1953-1964

Published Date: 17 April 2012

Concentration- and time-dependent response of human gingival fibroblasts to fibroblast growth factor 2 immobilized on titanium dental implants

Ma Q, Wang W, Chu PK, Mei S, Ji K, Jin L, Zhang Y,

International Journal of Nanomedicine 2012, 7:1965-1976

Published Date: 17 April 2012

Theranostic liposomes loaded with quantum dots and apomorphine for brain targeting and bioimaging

Wen CJ, Zhang LW, Al-Suwayeh SA, Yen TC, Fang JY

International Journal of Nanomedicine 2012, 7:1599-1611

Published Date: 26 March 2012

Investigation of glucose-modified liposomes using polyethylene glycols with different chain lengths as the linkers for brain targeting

Xie F, Yao N, Qin Y, Zhang Q, Chen H, Yuan M, Tang J, Li X, Fan W, Zhang Q, Wu Y, Hai L, He Q

International Journal of Nanomedicine 2012, 7:163-175

Published Date: 6 January 2012

Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease

Stricker RB, DeLong AK, Green CL, Savely VR, Chamallas SN, Johnson L

International Journal of General Medicine 2011, 4:639-646

Published Date: 6 September 2011

Power optimized variation aware dual-threshold SRAM cell design technique

Aminul Islam, Mohd Hasan

Nanotechnology, Science and Applications 2011, 4:25-33

Published Date: 10 February 2011

Organic functionalization of single-walled carbon nanotubes (SWCNTs) with some chemotherapeutic agents as a potential method for drug delivery

Ardeshir Khazaei, Mohammad Navid Soltani Rad, Maryam Kiani Borazjani

International Journal of Nanomedicine 2010, 5:639-645

Published Date: 30 August 2010

Applications of gold nanoparticles in cancer nanotechnology

Weibo Cai, Ting Gao, Hao Hong, Jiangtao Sun

Nanotechnology, Science and Applications 2008, 1:17-32

Published Date: 19 September 2008