In vitro and In vivo Characterization of 64Cu-Labeled AbegrinTM, a Humanized Monoclonal Antibody against Integrin αvβ3
| Autor: | Kai Chen, Qizhen Cao, David A. Tice, Xiaoyuan Chen, Yun Wu, Weibo Cai |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research Immunoconjugates medicine.drug_class Mice Nude Angiogenesis Inhibitors Breast Neoplasms Adenocarcinoma Antibodies Monoclonal Humanized Humanized antibody Monoclonal antibody Heterocyclic Compounds 1-Ring Mice chemistry.chemical_compound Pharmacokinetics In vivo Cell Line Tumor Organometallic Compounds medicine Animals Humans DOTA Tissue Distribution Radiometry neoplasms Chelating Agents Chemistry Antibodies Monoclonal Prostatic Neoplasms Integrin alphaVbeta3 Molecular biology Neoplasm Proteins Radiography Copper Radioisotopes Radioimmunodetection Oncology Positron-Emission Tomography Vitaxin Monoclonal Female Glioblastoma Preclinical imaging medicine.drug |
| Zdroj: | Cancer Research. 66:9673-9681 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | AbegrinTM (MEDI-522 or VitaxinTM), a humanized monoclonal antibody against human integrin αvβ3, is in clinical trials for cancer therapy. In vivo imaging using AbegrinTM-based probes is needed for better treatment monitoring and dose optimization. Here, we conjugated AbegrinTM with macrocyclic chelating agent 1,4,7,10-tetra-azacylododecane N,N′,N″,N‴-tetraacetic (DOTA) at five different DOTA/AbegrinTM ratios. The conjugates were labeled with 64Cu (half-life = 12.7 hours) and tested in three human (U87MG, MDA-MB-435, and PC-3) and one mouse (GL-26) tumor models. The in vitro and in vivo effects of these 64Cu-DOTA-AbegrinTM conjugates were evaluated. The number of DOTA per AbegrinTM varied from 1.65 ± 0.32 to 38.53 ± 5.71 and the radiolabeling yield varied from 5.20 ± 3.16% to 88.12 ± 6.98% (based on 2 mCi 64Cu per 50 μg DOTA-AbegrinTM conjugate). No significant difference in radioimmunoreactivity was found among these conjugates (between 59.78 ± 1.33 % and 71.13 ± 2.58 %). Micro-positron emission tomography studies revealed that 64Cu-DOTA-AbegrinTM (1,000:1) had the highest tumor activity accumulation (49.41 ± 4.54% injected dose/g at 71-hour postinjection for U87MG tumor). The receptor specificity of 64Cu-DOTA-Abegrin was confirmed by effective blocking of MDA-MB-435 tumor uptake with coadministration of nonradioactive Abegrin. 64Cu-DOTA-IgG exhibited background level tumor uptake at all time points examined. Integrin αvβ3-specific tumor imaging using 64Cu-DOTA-AbegrinTM may be translated into the clinic to characterize the pharmacokinetics, tumor targeting efficacy, dose optimization, and dose interval of AbegrinTM and/or Abegrin conjugates. Chemotherapeutics or radiotherapeutics using AbegrinTM as the delivering vehicle may also be effective in treating integrin αvβ3-positive tumors. (Cancer Res 2006; 66(19): 9673-81) |
| Databáze: | OpenAIRE |
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