Preclinical Evaluation of Monoclonal Antibody 14C5 for Targeting Pancreatic Cancer
| Autor: | Filip De Vos, Caroline Dumolyn, Liesbet Vervoort, Andrew M. Scott, Sarah K. Baird, Steven Staelens, Els Waegemans, Ingrid Burvenich, Magali Van Steenkiste |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Biodistribution Pathology medicine.medical_specialty medicine.drug_class Drug Evaluation Preclinical Radioimmunoassay Mice Nude Monoclonal antibody Iodine Radioisotopes Mice In vivo Pancreatic tumor Pancreatic cancer Tumor Cells Cultured medicine Animals Humans Receptors Vitronectin Tissue Distribution Radiology Nuclear Medicine and imaging Cell-substrate adhesion Pancreas Pharmacology biology Chemistry Antibodies Monoclonal General Medicine Pentetic Acid medicine.disease Xenograft Model Antitumor Assays Pancreatic Neoplasms Oncology Cancer research biology.protein Female CA19-9 Radiopharmaceuticals Antibody |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 25:193-205 |
| ISSN: | 1557-8852 1084-9785 |
| Popis: | 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 K(d)s. In vitro internalization experiments showed a longer intracellular retention of (111)In-p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA)-14C5 in comparison to (125)I-14C5 and (111)In-p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA)-14C5. In vivo radioisotope tumor uptake was maximum at 48-72 hours, with the uptake of (111)In-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 (131)I-14C5 (12.16 +/- 1.03%ID/g) and (111)In-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. |
| Databáze: | OpenAIRE |
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