Immuno-PET Quantitation of de2-7 Epidermal Growth Factor Receptor Expression in Glioma Using 124I-IMP-R4–Labeled Antibody ch806
| Autor: | Fook-Thean Lee, Terrance Grant Johns, Graeme O'Keefe, Lloyd J. Old, Angela Mountain, T. Saunder, Andrew M. Scott, Hui K Gan, Fiona E Smyth, Gareth Jones, David M. Goldenberg, Angela Rigopoulos, Serengulam V. Govindan, Jessica Sagona |
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| Rok vydání: | 2010 |
| Předmět: |
Biodistribution
medicine.drug_class Monoclonal antibody Iodine Radioisotopes Mice In vivo Epidermal growth factor Cell Line Tumor Glioma medicine Animals Humans Radiology Nuclear Medicine and imaging Amino Acid Sequence Epidermal growth factor receptor Receptor biology Chemistry Antibodies Monoclonal Pentetic Acid medicine.disease Molecular biology In vitro ErbB Receptors Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Positron-Emission Tomography biology.protein Female Tomography X-Ray Computed Oligopeptides |
| Zdroj: | Journal of Nuclear Medicine. 51:967-972 |
| ISSN: | 2159-662X 0161-5505 |
| Popis: | Overexpression, activation, and mutations of the epidermal growth factor receptor (EGFR) are commonly found in solid tumors. The aim of this study was to develop a PET-based method for detecting the constitutively active mutant de2-7 EGFR, which is associated with disease progression and resistance to chemotherapy and radiotherapy in glioma. Methods: The chimeric antibody ch806, which selectively binds an epitope of the EGFR that is exposed only on overexpressed, mutant, or ligand-activated forms of the receptor, was conjugated to the radiohalogen 124I via the residualizing ligand IMP-R4, and in vitro properties were characterized. In vivo biodistribution and small-animal PET studies were performed in BALB/c nude mice bearing U87MG.de2-7 glioma xenografts. Imaging results were correlated with measured tumor uptake of the radioconjugate. Results:124I-IMP-R4-ch806 had an immunoreactivity of 78.3% and was stable for 7 d when incubated in serum in vitro. The biodistribution analysis of 124I-IMP-R4-ch806 demonstrated a maximal uptake of 30.95 ± 6.01 percentage injected dose per gram (%ID/g) in U87MG.de2-7 xenografts at 48 h after injection, with prolonged tumor retention (6.07 ± 0.80 %ID/g at 216 h after injection). The tumor-to-blood ratio increased from 0.44 at 4 h after injection to a maximum of 4.70 at 168 h after injection. PET of 124I-IMP-R4-ch806 biodistribution was able to clearly detect the U87MG.de2-7 tumors at 24 h after injection and for at least 168 h after injection. Correlation between tumor PET image quantitation of 124I-IMP-R4-ch806 and %ID/g determined from resected tissues (r = 0.9350) was excellent. Conclusion: These results show that immuno-PET with 124I-IMP-R4-ch806 is feasible and allows noninvasive quantitation of de2-7 EGFR expression in vivo. |
| Databáze: | OpenAIRE |
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