Advanced search
1 file | 458.74 KB

Preclinical evaluation of monoclonal antibody 14C5 for targeting pancreatic cancer

Author
Organization
Abstract
The use of radiolabeled antibodies that are able to target primary tumors as well as metastatic tumor sites with minimal reactivity to normal tissues is a promising approach for treating pancreatic cancer. In this study, the integrin alpha(v)beta(5) is studied as a target for the diagnosis of and potential therapy for human pancreatic cancer by using the radiolabeled murine monoclonal antibody (mAb) 14C5. Biopsy specimens from human pancreatic tumors were examined for the expression of the integrin alpha(v)beta(5). The pancreatic tumor cell line Capan-1 was used to test the in vitro targeting potency of mAb 14C5 labeled with 125/131-iodine and 111-indium. Internalization, retention, and metabolism were investigated in cellular radioimmunoassays. Biodistribution and tumor-targeting characteristics were studied in Capan-1 xenografts. All tumor sections were positive for the integrin alpha(v)beta(5), with an extensive positive staining of the stroma. Saturation binding experiments showed high affinity with comparable KdS. In vitro internalization experiments showed a longer intracellular retention of In-111-p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA)-14C5 in comparison to I-125-14C5 and In-111-p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA)-14C5. In vivo radioisotope tumor uptake was maximum at 48-72 hours, with the uptake of In-111-p-SCN-Bz-DOTA-14C5 (35.84 +/- 8.64 percentage of injected dose per g [% ID/g]) being 3.9- and 2.2-folds higher than I-131-14C5 (12.16 +/- 1.03% ID/g) and In-111-p-SCN-Bz-DTPA-14C5 (14.30 +/- 3.76% ID/g), respectively. Planar gamma imaging with mAb 14C5 indicated clear localization of the pancreatic tumors versus minimal normal tissue uptake. mAb 14C5 is a promising new antibody for targeting the integrin alpha(v)beta(5) for the diagnosis of and potential therapy for pancreatic cancer.
Keywords
TUMOR XENOGRAFTS, PROSTATE-CANCER, IN-VIVO, NUDE-MICE BEARING, CELL SUBSTRATE ADHESION, pancreatic cancer, radioimmunodetection, 131-iodine, monoclonal antibody, 111-indium, STELLATE CELLS, PHASE-I, BIODISTRIBUTION, CARCINOMA, THERAPY

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 458.74 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Vervoort, Liesbet, Ingrid Burvenich, Steven Staelens, Caroline Dumolyn, Els Waegemans, Magali Van Steenkiste, Sarah K Baird, Andrew M Scott, and Filip De Vos. 2010. “Preclinical Evaluation of Monoclonal Antibody 14C5 for Targeting Pancreatic Cancer.” Cancer Biotherapy and Radiopharmaceuticals 25 (2): 193–207.
APA
Vervoort, Liesbet, Burvenich, I., Staelens, S., Dumolyn, C., Waegemans, E., Van Steenkiste, M., Baird, S. K., et al. (2010). Preclinical evaluation of monoclonal antibody 14C5 for targeting pancreatic cancer. CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS, 25(2), 193–207.
Vancouver
1.
Vervoort L, Burvenich I, Staelens S, Dumolyn C, Waegemans E, Van Steenkiste M, et al. Preclinical evaluation of monoclonal antibody 14C5 for targeting pancreatic cancer. CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS. 2010;25(2):193–207.
MLA
Vervoort, Liesbet, Ingrid Burvenich, Steven Staelens, et al. “Preclinical Evaluation of Monoclonal Antibody 14C5 for Targeting Pancreatic Cancer.” CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS 25.2 (2010): 193–207. Print.
@article{980117,
  abstract     = {The use of radiolabeled antibodies that are able to target primary tumors as well as metastatic tumor sites with minimal reactivity to normal tissues is a promising approach for treating pancreatic cancer. In this study, the integrin alpha(v)beta(5) is studied as a target for the diagnosis of and potential therapy for human pancreatic cancer by using the radiolabeled murine monoclonal antibody (mAb) 14C5. Biopsy specimens from human pancreatic tumors were examined for the expression of the integrin alpha(v)beta(5). The pancreatic tumor cell line Capan-1 was used to test the in vitro targeting potency of mAb 14C5 labeled with 125/131-iodine and 111-indium. Internalization, retention, and metabolism were investigated in cellular radioimmunoassays. Biodistribution and tumor-targeting characteristics were studied in Capan-1 xenografts. All tumor sections were positive for the integrin alpha(v)beta(5), with an extensive positive staining of the stroma. Saturation binding experiments showed high affinity with comparable KdS. In vitro internalization experiments showed a longer intracellular retention of In-111-p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA)-14C5 in comparison to I-125-14C5 and In-111-p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA)-14C5. In vivo radioisotope tumor uptake was maximum at 48-72 hours, with the uptake of In-111-p-SCN-Bz-DOTA-14C5 (35.84 +/- 8.64 percentage of injected dose per g [\% ID/g]) being 3.9- and 2.2-folds higher than I-131-14C5 (12.16 +/- 1.03\% ID/g) and In-111-p-SCN-Bz-DTPA-14C5 (14.30 +/- 3.76\% ID/g), respectively. Planar gamma imaging with mAb 14C5 indicated clear localization of the pancreatic tumors versus minimal normal tissue uptake. mAb 14C5 is a promising new antibody for targeting the integrin alpha(v)beta(5) for the diagnosis of and potential therapy for pancreatic cancer.},
  author       = {Vervoort, Liesbet and Burvenich, Ingrid  and Staelens, Steven and Dumolyn, Caroline and Waegemans, Els and Van Steenkiste, Magali and Baird, Sarah K and Scott, Andrew M and De Vos, Filip},
  issn         = {1084-9785},
  journal      = {CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS},
  keyword      = {TUMOR XENOGRAFTS,PROSTATE-CANCER,IN-VIVO,NUDE-MICE BEARING,CELL SUBSTRATE ADHESION,pancreatic cancer,radioimmunodetection,131-iodine,monoclonal antibody,111-indium,STELLATE CELLS,PHASE-I,BIODISTRIBUTION,CARCINOMA,THERAPY},
  language     = {eng},
  number       = {2},
  pages        = {193--207},
  title        = {Preclinical evaluation of monoclonal antibody 14C5 for targeting pancreatic cancer},
  url          = {http://dx.doi.org/10.1089/cbr.2009.0696},
  volume       = {25},
  year         = {2010},
}

Altmetric
View in Altmetric
Web of Science
Times cited: