Abstract | BACKGROUND AND OBJECTIVE: METHODS:
Cetuximab was coupled with an N-sulfosuccinimide ester of DOTA, purified, and labeled with the positron-emitting nuclide, 64Cu. Receptor-binding specificity and affinity of 64Cu-DOTA-cetuximab were studied using human MDA-MB-468 breast cancer cells, which express high levels of EGFR. Micropositron emission tomography and biodistribution studies were performed in athymic nude mice bearing MDA-MB-468 cell xenografts. Blocking studies with cold cetuximab were also performed to determine the specific binding of cetuximab. RESULTS: The radiochemical yield was 97.1 ± 1.1%. The specific activity was 1.5 Ci/μm cetuximab and the affinity to EGFR-positive MDA-MB-468 cells was high (KD=0.4 nmol/l). Both biodistribution and micropositron emission tomographic imaging studies with 64Cu-DOTA-cetuximab showed higher tumor uptake at 24 h (20.91 ± 2.49% ID/g, standardized uptake values of 9.6) than at 4 h (11.65 ± 3.89% ID/g, standardized uptake values of 4.9). Tumor uptake was significantly reduced from 20.91 ± 2.49% ID/g at 24 h to 14.42 ± 0.85% ID/g in a 1-h blocking study (P=0.00). CONCLUSION:
Cetuximab can be labeled with 64Cu without compromising its biological activity. The tumor uptake was excellent with high tumor/muscle (7.97 ± 1.78 at 4 h, 15.91 ± 6.04 at 24 h) and reasonable tumor/blood (0.5 ± 0.18 at 4 h, 2.12 ± 0.86 at 24 h) ratios. Blocking studies showed the specific binding of the labeled antibody to tumor tissue.
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Authors | Kayvan Sadri, Qing Ren, Kaijun Zhang, Bishnuhari Paudyal, Devakumar Devadhas, Ulrich Rodeck, Mathew Thakur |
Journal | Nuclear medicine communications
(Nucl Med Commun)
Vol. 32
Issue 7
Pg. 563-9
(Jul 2011)
ISSN: 1473-5628 [Electronic] England |
PMID | 21572364
(Publication Type: Journal Article)
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Chemical References |
- 64Cu-DOTA-cetuximab
- Antibodies, Monoclonal
- Organometallic Compounds
- ErbB Receptors
- Cetuximab
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Topics |
- Adenocarcinoma
(diagnostic imaging, genetics, metabolism, pathology)
- Animals
- Antibodies, Monoclonal
(chemistry, metabolism, pharmacokinetics)
- Breast Neoplasms
(diagnostic imaging, genetics, metabolism, pathology)
- Cell Line, Tumor
- Cell Transformation, Neoplastic
- Cetuximab
- ErbB Receptors
(metabolism)
- Gene Expression Regulation, Neoplastic
- Humans
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Organometallic Compounds
(chemistry, metabolism, pharmacokinetics)
- Positron-Emission Tomography
(methods)
- Radiochemistry
- Time Factors
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