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Predicting cetuximab accumulation in ${it KRAS}$ wild-type and ${it KRAS}$ mutant colorectal cancer using $$^{64}$$Cu-labeled cetuximab positron emission tomography

Achmad, A.*; Hanaoka, Hirofumi*; Yoshioka, Hiroki*; Yamamoto, Shinji*; Tominaga, Hideyuki*; Araki, Takuya*; Ohshima, Yasuhiro; Oriuchi, Noboru*; Endo, Keigo*

Overexpression of epidermal growth factor receptor (EGFR) is common in colorectal cancer. However, cetuximab, an EGFR-targeting drug, is useful only for a subset of patients and no single predictor other than V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (${it KRAS}$) mutation status has been established. In this study, we investigated cetuximab accumulation in colorectal tumors using $$^{111}$$In-DOTA-cetuximab, and evaluated the potential of positron emission tomography (PET) imaging of $$^{64}$$Cu-DOTA-cetuximab. We found that ${it KRAS}$ wild-type tumors had significantly higher $$^{111}$$In-DOTA-cetuximab accumulation than ${it KRAS}$ mutant tumors. Based on ${it KRAS}$ mutation status, a strong correlation was found between $$^{111}$$In-DOTA-cetuximab tumor uptake and EGFR expression level. Significant correlation was also found between tumor uptake of $$^{111}$$In-DOTA-cetuximab and $$^{64}$$Cu-DOTA-cetuximab. PET imaging with $$^{64}$$Cu-DOTA-cetuximab effectively visualized cetuximab accumulation in colorectal tumors with a wide variety of EGFR expression levels and different ${it KRAS}$ mutation status as commonly encountered in the clinical setting. Our findings suggest that this radioimmunoimaging can be clinically translated as an in vivo tool to predict cetuximab accumulation in colorectal cancer patients prior to cetuximab therapy.



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