| Abstract: |
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. COPYRIGHT © 2010 by the Society of Nuclear Medicine, Inc. |
| Keywords: |
controlled study; protein expression; unclassified drug; human cell; genetics; disease course; nonhuman; positron emission tomography; glioma; methodology; mouse; animal; metabolism; animals; mice; computer assisted tomography; epidermal growth factor receptor; animal experiment; animal model; tomography, x-ray computed; in vivo study; receptor, epidermal growth factor; in vitro study; tumor xenograft; peptide; cell line, tumor; immunoreactivity; cell transformation, neoplastic; monoclonal antibody; gene expression regulation; gene expression regulation, neoplastic; antibodies, monoclonal; amino acid sequence; diagnostic agent; radioactive iodine; isotope labeling; iodine radioisotopes; cell transformation; tumor cell line; positron-emission tomography; drug derivative; scintiscanning; radiography; iodine 124; pet; oligopeptides; mutant epidermal growth factor receptor; chimeric antibody; chimeric antibody ch806; peptide imp r4; 4 (n maleimidomethyl)cyclohexane 1 carbonyllysyl(4 (n maleimidomethyl)cyclohexane 1 carbonyl) lysyl(1 ((4 thiocarbonylamino)benzyl)diethylenetriaminepentaacetic acid) tyrosyl lysine(1 ((4 thiocarbonylamino)benzyl)diethylenetriaminepentaacetic acid); 4-(n-maleimidomethyl)cyclohexane-1-carbonyllysyl(4-(n-maleimidomethyl)cyclohexane-1-carbonyl)-lysyl(1-((4-thiocarbonylamino)benzyl)diethylenetriaminepentaacetic acid)-tyrosyl-lysine(1-((4-thiocarbonylamino)benzyl)diethylenetriaminepentaacetic acid); monoclonal antibody 806; oligopeptide; pentetic acid
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