Abstract | UNLABELLED: METHODS:
Cetuximab was conjugated to the bifunctional chelator DOTA and labeled with (64)Cu. EGFR messenger RNA ( mRNA) expression was correlated with EGFR densities on the cell surface of 5 different cervical cancer cell lines and with receptor function, measured by internalization of (64)Cu-DOTA-cetuximab. Imaging in tumor-bearing mice with small-animal PET was performed using the highest-expressing cervical cancer cell line. RESULTS: The affinity of (64)Cu-DOTA-cetuximab binding for the EGFR was similar in 4 EGFR-positive lines, varying from 0.1 to 0.7 nM. The mRNA expression corresponded well with EGFR densities and levels of internalization, with responses decreasing in the order of CaSki>ME-180>DoTc2 4510>HeLa>C-33A. Biodistribution and small-animal PET studies with (64)Cu-DOTA-cetuximab in CaSki tumor-bearing nude mice showed relatively high tumor uptake at 24 h after injection (13.2+/-1.2 percentage of injected activity per gram), although there was also significant retention of activity in the blood and liver accumulation. CONCLUSION: (64)Cu-DOTA-cetuximab was successfully used to detect and quantify EGFR expression in cervical cancer tumors, and small-animal PET/CT of EGFR-expressing CaSki tumors suggests potential for PET/CT of EGFR-positive tumors.
|
Authors | Martin Eiblmaier, Laura A Meyer, Mark A Watson, Paula M Fracasso, Linda J Pike, Carolyn J Anderson |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 49
Issue 9
Pg. 1472-9
(Sep 2008)
ISSN: 0161-5505 [Print] United States |
PMID | 18703609
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- 64Cu-DOTA-cetuximab
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Organometallic Compounds
- ErbB Receptors
- Cetuximab
|
Topics |
- Animals
- Antibodies, Monoclonal
(pharmacokinetics, therapeutic use)
- Antibodies, Monoclonal, Humanized
- Cell Line, Tumor
- Cetuximab
- Drug Delivery Systems
(methods)
- ErbB Receptors
(metabolism)
- Female
- HeLa Cells
- Humans
- Metabolic Clearance Rate
- Mice
- Mice, SCID
- Organ Specificity
- Organometallic Compounds
(pharmacokinetics, therapeutic use)
- Radionuclide Imaging
- Statistics as Topic
- Tissue Distribution
- Uterine Cervical Neoplasms
(diagnostic imaging, metabolism)
|