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99mTc-labeled tricarbonyl His-CNA35 as an imaging agent for the detection of tumor vasculature

Gilles Mees UGent, Rudi Dierckx UGent, Koen Mertens UGent, Simon Vermeire UGent, Magali Van Steenkiste UGent, Chris Reutelingsperger, Yves D'Asseler UGent, Kathelijne Peremans UGent, Nancy Van Damme UGent and Christophe Van De Wiele UGent (2012) JOURNAL OF NUCLEAR MEDICINE. 53(3). p.464-471
abstract
Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature. Methods: Tc-99m-tricarbonyl was prepared and labeled with His-collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. Tc-99m-(CO)(3) His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft. Results: The labeling procedure yielded a compound with 95%-99% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. Tc-99m-(CO)(3) His-CNA35 rapidly cleared from the blood and pre-dominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of Tc-99m-(CO)(3) His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature. Conclusion: Tc-99m-(CO)(3) His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.
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author
organization
alternative title
Tc-99m-labeled tricarbonyl His-CNA35 as an imaging agent for the detection of tumor vasculature
year
type
journalArticle (original)
publication status
published
subject
keyword
VISUALIZATION, PROTEINS, NORMALIZATION, ANGIOGENESIS, COLLAGEN, INTEGRIN, CANCER, POSITRON-EMISSION-TOMOGRAPHY, HT29, CNA35, tricarbonyl, tumor vasculature, THERAPY, BINDING
journal title
JOURNAL OF NUCLEAR MEDICINE
J. Nucl. Med.
volume
53
issue
3
pages
464 - 471
Web of Science type
Article
Web of Science id
000301194300044
JCR category
RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
JCR impact factor
5.774 (2012)
JCR rank
6/119 (2012)
JCR quartile
1 (2012)
ISSN
0161-5505
DOI
10.2967/jnumed.111.095794
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2152777
handle
http://hdl.handle.net/1854/LU-2152777
date created
2012-06-14 09:54:53
date last changed
2012-07-10 16:01:13
@article{2152777,
  abstract     = {Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature. Methods: Tc-99m-tricarbonyl was prepared and labeled with His-collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. Tc-99m-(CO)(3) His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft. Results: The labeling procedure yielded a compound with 95\%-99\% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. Tc-99m-(CO)(3) His-CNA35 rapidly cleared from the blood and pre-dominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of Tc-99m-(CO)(3) His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature. Conclusion: Tc-99m-(CO)(3) His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.},
  author       = {Mees, Gilles and Dierckx, Rudi and Mertens, Koen and Vermeire, Simon and Van Steenkiste, Magali and Reutelingsperger, Chris and D'Asseler, Yves and Peremans, Kathelijne and Van Damme, Nancy and Van De Wiele, Christophe},
  issn         = {0161-5505},
  journal      = {JOURNAL OF NUCLEAR MEDICINE},
  keyword      = {VISUALIZATION,PROTEINS,NORMALIZATION,ANGIOGENESIS,COLLAGEN,INTEGRIN,CANCER,POSITRON-EMISSION-TOMOGRAPHY,HT29,CNA35,tricarbonyl,tumor vasculature,THERAPY,BINDING},
  language     = {eng},
  number       = {3},
  pages        = {464--471},
  title        = {99mTc-labeled tricarbonyl His-CNA35 as an imaging agent for the detection of tumor vasculature},
  url          = {http://dx.doi.org/10.2967/jnumed.111.095794},
  volume       = {53},
  year         = {2012},
}

Chicago
Mees, Gilles, Rudi Dierckx, Koen Mertens, Simon Vermeire, Magali Van Steenkiste, Chris Reutelingsperger, Yves D’Asseler, Kathelijne Peremans, Nancy Van Damme, and Christophe Van De Wiele. 2012. “99mTc-labeled Tricarbonyl His-CNA35 as an Imaging Agent for the Detection of Tumor Vasculature.” Journal of Nuclear Medicine 53 (3): 464–471.
APA
Mees, G., Dierckx, R., Mertens, K., Vermeire, S., Van Steenkiste, M., Reutelingsperger, C., D’Asseler, Y., et al. (2012). 99mTc-labeled tricarbonyl His-CNA35 as an imaging agent for the detection of tumor vasculature. JOURNAL OF NUCLEAR MEDICINE, 53(3), 464–471.
Vancouver
1.
Mees G, Dierckx R, Mertens K, Vermeire S, Van Steenkiste M, Reutelingsperger C, et al. 99mTc-labeled tricarbonyl His-CNA35 as an imaging agent for the detection of tumor vasculature. JOURNAL OF NUCLEAR MEDICINE. 2012;53(3):464–71.
MLA
Mees, Gilles, Rudi Dierckx, Koen Mertens, et al. “99mTc-labeled Tricarbonyl His-CNA35 as an Imaging Agent for the Detection of Tumor Vasculature.” JOURNAL OF NUCLEAR MEDICINE 53.3 (2012): 464–471. Print.