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99mTc-(CO)3 His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab

CHRISTEL VANGESTEL UGent, Christophe Van De Wiele UGent, Nancy Van Damme UGent, Steven Staelens, Patrick Pauwels, Chris PM Reutelingsperger and Marc Peeters UGent (2011) JOURNAL OF NUCLEAR MEDICINE. 52(11). p.1786-1794
abstract
Colorectal tumors are dependent on angiogenesis for growth, and vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Antiangiogenic drugs can induce a transient normalization of the tumor vasculature with improved delivery of coadministered chemotherapy. The efficacy of antihuman VEGF antibody (bevacizumab) with or without irinotecan was evaluated in a colorectal cancer xenograft using Tc-99m-(CO)(3) His-annexin A5. Methods: Colo205-bearing mice were treated with a single dose of bevacizumab (5 mg/kg) during 2, 4, or 6 d. Microvessel density, pericyte coverage (alpha-smooth-muscle actin immunostaining), collagen-covered tumor vessels (Masson trichrome staining), and tumor hypoxic fraction (pimonidazole staining) were determined at the 3 different time points after treatment with bevacizumab. To investigate the possible synergistic effects of combination therapy with bevacizumab and irinotecan, Colo205-bearing mice were treated with a single dose of bevacizumab 2, 4, or 6 d before administration of a single dose of irinotecan (100 mg/kg) or 0.9% NaCl. The apoptosis-detecting radiotracer Tc-99m-(CO)(3) His-annexin A5 was injected (18.5 MBq) in mice 12, 24, and 48 h after the start of the irinotecan or NaCl treatment, and micro-SPECT was subsequently performed 3.5 h after injection of the radiotracer. Results were correlated to histologic analysis for apoptosis (caspase-3 activation). Results: Four days after bevacizumab administration, microvessel density decreased significantly, and alpha-smooth-muscle actin and collagen-covered vessels, compared with control tumors, were increased, suggesting normalization of the tumor vasculature. Hypoxic fraction was slightly reduced 4 d after treatment with bevacizumab. SPECT analyses demonstrated a significant increase in tumoral Tc-99m-(CO)(3) His-annexin A5 uptake 4 d after bevacizumab treatment and 24 h after irinotecan administration (232.78 +/- 24.82 percentage injected dose/tumor weight [g]/body weight [kg], P < 0.05), compared with each monotherapy, indicating a synergistic effect of both therapies. Conclusion: Tc-99m-(CO)(3) His-annexin A5 micro-SPECT demonstrates increased antitumor activity of irinotecan during the transient vascular normalization period caused by bevacizumab. Our data outline the importance of timing of combined anti-VEGF treatment with chemotherapy.
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author
organization
alternative title
Tc-99m-(CO)(3) His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab
year
type
journalArticle (original)
publication status
published
subject
keyword
CANCER, TUMORS, RADIATION, ANTIBODY, colorectal cancer, APOPTOSIS, THERAPY, chemotherapy delivery, Tc-99m-(CO)(3) His-annexin A5, vascular normalization, anti-VEGF
journal title
JOURNAL OF NUCLEAR MEDICINE
J. Nucl. Med.
volume
52
issue
11
pages
1786 - 1794
Web of Science type
Article
Web of Science id
000296722000025
JCR category
RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
JCR impact factor
6.381 (2011)
JCR rank
1/116 (2011)
JCR quartile
1 (2011)
ISSN
0161-5505
DOI
10.2967/jnumed.111.092650
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2141566
handle
http://hdl.handle.net/1854/LU-2141566
date created
2012-06-13 10:45:10
date last changed
2012-06-26 12:14:51
@article{2141566,
  abstract     = {Colorectal tumors are dependent on angiogenesis for growth, and vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Antiangiogenic drugs can induce a transient normalization of the tumor vasculature with improved delivery of coadministered chemotherapy. The efficacy of antihuman VEGF antibody (bevacizumab) with or without irinotecan was evaluated in a colorectal cancer xenograft using Tc-99m-(CO)(3) His-annexin A5. Methods: Colo205-bearing mice were treated with a single dose of bevacizumab (5 mg/kg) during 2, 4, or 6 d. Microvessel density, pericyte coverage (alpha-smooth-muscle actin immunostaining), collagen-covered tumor vessels (Masson trichrome staining), and tumor hypoxic fraction (pimonidazole staining) were determined at the 3 different time points after treatment with bevacizumab. To investigate the possible synergistic effects of combination therapy with bevacizumab and irinotecan, Colo205-bearing mice were treated with a single dose of bevacizumab 2, 4, or 6 d before administration of a single dose of irinotecan (100 mg/kg) or 0.9\% NaCl. The apoptosis-detecting radiotracer Tc-99m-(CO)(3) His-annexin A5 was injected (18.5 MBq) in mice 12, 24, and 48 h after the start of the irinotecan or NaCl treatment, and micro-SPECT was subsequently performed 3.5 h after injection of the radiotracer. Results were correlated to histologic analysis for apoptosis (caspase-3 activation). Results: Four days after bevacizumab administration, microvessel density decreased significantly, and alpha-smooth-muscle actin and collagen-covered vessels, compared with control tumors, were increased, suggesting normalization of the tumor vasculature. Hypoxic fraction was slightly reduced 4 d after treatment with bevacizumab. SPECT analyses demonstrated a significant increase in tumoral Tc-99m-(CO)(3) His-annexin A5 uptake 4 d after bevacizumab treatment and 24 h after irinotecan administration (232.78 +/- 24.82 percentage injected dose/tumor weight [g]/body weight [kg], P {\textlangle} 0.05), compared with each monotherapy, indicating a synergistic effect of both therapies. Conclusion: Tc-99m-(CO)(3) His-annexin A5 micro-SPECT demonstrates increased antitumor activity of irinotecan during the transient vascular normalization period caused by bevacizumab. Our data outline the importance of timing of combined anti-VEGF treatment with chemotherapy.},
  author       = {VANGESTEL, CHRISTEL and Van De Wiele, Christophe and Van Damme, Nancy and Staelens, Steven and Pauwels, Patrick and Reutelingsperger, Chris PM and Peeters, Marc},
  issn         = {0161-5505},
  journal      = {JOURNAL OF NUCLEAR MEDICINE},
  keyword      = {CANCER,TUMORS,RADIATION,ANTIBODY,colorectal cancer,APOPTOSIS,THERAPY,chemotherapy delivery,Tc-99m-(CO)(3) His-annexin A5,vascular normalization,anti-VEGF},
  language     = {eng},
  number       = {11},
  pages        = {1786--1794},
  title        = {99mTc-(CO)3 His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab},
  url          = {http://dx.doi.org/10.2967/jnumed.111.092650},
  volume       = {52},
  year         = {2011},
}

Chicago
VANGESTEL, CHRISTEL, Christophe Van De Wiele, Nancy Van Damme, Steven Staelens, Patrick Pauwels, Chris PM Reutelingsperger, and Marc Peeters. 2011. “99mTc-(CO)3 His-annexin A5 micro-SPECT Demonstrates Increased Cell Death by Irinotecan During the Vascular Normalization Window Caused by Bevacizumab.” Journal of Nuclear Medicine 52 (11): 1786–1794.
APA
VANGESTEL, C., Van De Wiele, C., Van Damme, N., Staelens, S., Pauwels, P., Reutelingsperger, C. P., & Peeters, M. (2011). 99mTc-(CO)3 His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab. JOURNAL OF NUCLEAR MEDICINE, 52(11), 1786–1794.
Vancouver
1.
VANGESTEL C, Van De Wiele C, Van Damme N, Staelens S, Pauwels P, Reutelingsperger CP, et al. 99mTc-(CO)3 His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab. JOURNAL OF NUCLEAR MEDICINE. 2011;52(11):1786–94.
MLA
VANGESTEL, CHRISTEL, Christophe Van De Wiele, Nancy Van Damme, et al. “99mTc-(CO)3 His-annexin A5 micro-SPECT Demonstrates Increased Cell Death by Irinotecan During the Vascular Normalization Window Caused by Bevacizumab.” JOURNAL OF NUCLEAR MEDICINE 52.11 (2011): 1786–1794. Print.