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SPECT imaging with 99mTc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression

Lieven Huang, Lea Olive Tchouate Gainkam, Vicky Caveliers, Christian Vanhove UGent, Marleen Keyaerts, Patrick De Baetselier, Axel Bossuyt, Hilde Revets and Tony Lahoutte (2008) MOLECULAR IMAGING AND BIOLOGY. 10(3). p.167-175
abstract
Purpose: Overexpression of the epidermal growth factor receptor (EGFR) occurs with high incidence in various carcinomas. The oncogenic expression of the receptor has been exploited for immunoglobulin-based diagnostics and therapeutics. We describe the use of a llama single-domain antibody fragment, termed Nanobody (R), for the in vivo radioimmunodetection of EGFR overexpressing tumors using single photon emission computed tomography (SPECT) in mice. Methods: Fluorescence-activated cell sorting (FACS) analysis was performed to evaluate the specificity and selectivity of 8B6 Nanobody to bind EGFR on EGFR overexpressing cells. The Nanobody was then labeled with (99m)Tc via its C-terminal histidine tail. Uptake in normal organs and tissues was assessed by ex vivo analysis. In vivo tumor targeting of (99m)Tc-8B6 Nanobody was evaluated via pinhole SPECT in mice bearing xenografts of tumor cells with either high (A431) or moderate (DU145) overexpression of EGFR. Results: FACS analysis indicated that the 8B6 Nanobody only recognizes cells overexpressing EGFR. In vivo blood clearance of (99m)Tc-8B6 Nanobody is relatively fast (half-life, 1.5 h) and mainly via the kidneys. At 3 h postinjection, total kidney accumulation is high (46.6 +/- 0.9%IA) compared to total liver uptake (18.9 +/- 0.6%IA). Pinhole SPECT imaging of mice bearing A431 xenografts showed higher average tumor uptake (5.2+0.5%IA/cm(3)) of (99m)Tc-8B6 Nanobody compared to DU145 xenografts (1.8+0.3%IA/cm(3), p<0.001). Conclusion: The EGFR-binding Nanobody investigated in this study shows high specificity and selectivity towards EGFR overexpressing cells. Pinhole SPECT analysis with (99m)Tc-8B6 Nanobody enabled in vivo discrimination between tumors with high and moderate EGFR overexpression. The favorable biodistribution further corroborates the suitability of Nanobodies for in vivo tumor imaging.
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author
organization
alternative title
SPECT imaging with (99m)Tc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression
year
type
journalArticle (original)
publication status
published
subject
keyword
nanobody, EGFR, tumor targeting, molecular imaging, diagnosis, biodistribution, biomarker, EPIDERMAL-GROWTH-FACTOR, HEAVY-CHAIN ANTIBODIES, SINGLE-DOMAIN ANTIBODY, COLORECTAL-CANCER PATIENTS, HUMAN-TUMOR XENOGRAFTS, HUMAN BREAST-CANCER, BEARING NUDE-MICE, FACTOR RECEPTOR, MONOCLONAL-ANTIBODY, AFFIBODY MOLECULES
journal title
MOLECULAR IMAGING AND BIOLOGY
Mol. Imaging. Biol.
volume
10
issue
3
pages
167 - 175
Web of Science type
Article
Web of Science id
000255680100007
JCR category
RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
JCR impact factor
3.372 (2008)
JCR rank
18/90 (2008)
JCR quartile
1 (2008)
ISSN
1536-1632
DOI
10.1007/s11307-008-0133-8
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
420999
handle
http://hdl.handle.net/1854/LU-420999
date created
2008-06-25 09:39:00
date last changed
2013-02-12 10:45:06
@article{420999,
  abstract     = {Purpose: Overexpression of the epidermal growth factor receptor (EGFR) occurs with high incidence in various carcinomas. The oncogenic expression of the receptor has been exploited for immunoglobulin-based diagnostics and therapeutics. We describe the use of a llama single-domain antibody fragment, termed Nanobody (R), for the in vivo radioimmunodetection of EGFR overexpressing tumors using single photon emission computed tomography (SPECT) in mice. 
Methods: Fluorescence-activated cell sorting (FACS) analysis was performed to evaluate the specificity and selectivity of 8B6 Nanobody to bind EGFR on EGFR overexpressing cells. The Nanobody was then labeled with (99m)Tc via its C-terminal histidine tail. Uptake in normal organs and tissues was assessed by ex vivo analysis. In vivo tumor targeting of (99m)Tc-8B6 Nanobody was evaluated via pinhole SPECT in mice bearing xenografts of tumor cells with either high (A431) or moderate (DU145) overexpression of EGFR. 
Results: FACS analysis indicated that the 8B6 Nanobody only recognizes cells overexpressing EGFR. In vivo blood clearance of (99m)Tc-8B6 Nanobody is relatively fast (half-life, 1.5 h) and mainly via the kidneys. At 3 h postinjection, total kidney accumulation is high (46.6 +/- 0.9\%IA) compared to total liver uptake (18.9 +/- 0.6\%IA). Pinhole SPECT imaging of mice bearing A431 xenografts showed higher average tumor uptake (5.2+0.5\%IA/cm(3)) of (99m)Tc-8B6 Nanobody compared to DU145 xenografts (1.8+0.3\%IA/cm(3), p{\textlangle}0.001). 
Conclusion: The EGFR-binding Nanobody investigated in this study shows high specificity and selectivity towards EGFR overexpressing cells. Pinhole SPECT analysis with (99m)Tc-8B6 Nanobody enabled in vivo discrimination between tumors with high and moderate EGFR overexpression. The favorable biodistribution further corroborates the suitability of Nanobodies for in vivo tumor imaging.},
  author       = {Huang, Lieven and Gainkam, Lea Olive Tchouate and Caveliers, Vicky and Vanhove, Christian and Keyaerts, Marleen and De Baetselier, Patrick and Bossuyt, Axel and Revets, Hilde and Lahoutte, Tony},
  issn         = {1536-1632},
  journal      = {MOLECULAR IMAGING AND BIOLOGY},
  keyword      = {nanobody,EGFR,tumor targeting,molecular imaging,diagnosis,biodistribution,biomarker,EPIDERMAL-GROWTH-FACTOR,HEAVY-CHAIN ANTIBODIES,SINGLE-DOMAIN ANTIBODY,COLORECTAL-CANCER PATIENTS,HUMAN-TUMOR XENOGRAFTS,HUMAN BREAST-CANCER,BEARING NUDE-MICE,FACTOR RECEPTOR,MONOCLONAL-ANTIBODY,AFFIBODY MOLECULES},
  language     = {eng},
  number       = {3},
  pages        = {167--175},
  title        = {SPECT imaging with 99mTc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression},
  url          = {http://dx.doi.org/10.1007/s11307-008-0133-8},
  volume       = {10},
  year         = {2008},
}

Chicago
Huang, Lieven, Lea Olive Tchouate Gainkam, Vicky Caveliers, Christian Vanhove, Marleen Keyaerts, Patrick De Baetselier, Axel Bossuyt, Hilde Revets, and Tony Lahoutte. 2008. “SPECT Imaging with 99mTc-labeled EGFR-specific Nanobody for in Vivo Monitoring of EGFR Expression.” Molecular Imaging and Biology 10 (3): 167–175.
APA
Huang, L., Gainkam, L. O. T., Caveliers, V., Vanhove, C., Keyaerts, M., De Baetselier, P., Bossuyt, A., et al. (2008). SPECT imaging with 99mTc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression. MOLECULAR IMAGING AND BIOLOGY, 10(3), 167–175.
Vancouver
1.
Huang L, Gainkam LOT, Caveliers V, Vanhove C, Keyaerts M, De Baetselier P, et al. SPECT imaging with 99mTc-labeled EGFR-specific nanobody for in vivo monitoring of EGFR expression. MOLECULAR IMAGING AND BIOLOGY. 2008;10(3):167–75.
MLA
Huang, Lieven, Lea Olive Tchouate Gainkam, Vicky Caveliers, et al. “SPECT Imaging with 99mTc-labeled EGFR-specific Nanobody for in Vivo Monitoring of EGFR Expression.” MOLECULAR IMAGING AND BIOLOGY 10.3 (2008): 167–175. Print.