TY - JOUR T1 - Immuno-PET Quantitation of de2-7 Epidermal Growth Factor Receptor Expression in Glioma Using <sup>124</sup>I-IMP-R4–Labeled Antibody ch806 JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 967 LP - 972 DO - 10.2967/jnumed.109.068395 VL - 51 IS - 6 AU - Fook T. Lee AU - Graeme J. O'Keefe AU - Hui K. Gan AU - Angela J. Mountain AU - Gareth R. Jones AU - Timothy H. Saunder AU - Jessica Sagona AU - Angela Rigopoulos AU - Fiona E. Smyth AU - Terrance G. Johns AU - Serengulam V. Govindan AU - David M. Goldenberg AU - Lloyd J. Old AU - Andrew M. Scott Y1 - 2010/06/01 UR - http://jnm.snmjournals.org/content/51/6/967.abstract N2 - 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. ER -