title: 18F-fluorothymidine PET/CT as an early predictor of tumor response to treatment with cetuximab in human lung cancer xenografts.
abstract: We investigated whether 18F-fluorothymidine-positron-emission tomography/computed tomography (18F-FLT-PET/CT) is useful for the evaluation of the very early response to anti-epidermal growth factor receptor (EGFR) antibody cetuximab therapy in human lung cancer xenografts. A human tumor xenograft model was established with a human non-small cell lung cancer cell line. The mice were randomly assigned to four groups: tumor growth follow-up, ex vivo study, PET/CT imaging and non-treated control. Mice were administered saline as control or cetuximab on day 1. An immunohistochemical study with Ki-67 was performed. Tumor volume treated with cetuximab was kept significantly smaller than control after day 8, although there was no difference on day 3. On day 3, 18F-FLT distribution was higher in the tumor than in other tissues, and was significantly decreased by treatment with cetuximab. On PET/CT imaging, 18F-FLT distribution in the tumor was clearly visualized, and the maximum standardized uptake value (SUV) was significantly decreased after treatment with cetuximab (p<0.01). Ki-67 expression was also significantly decreased on day 3 (p=0.01). These results suggest that 18F-FLT-PET/CT can be a useful predictor to determine the response to molecular targeted drugs such as cetuximab at an earlier time point than the change of tumor size.
authors.affiliation: Department of Medical Oncology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hatano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D014183:Transplantation, Heterologous; D047368:Tumor Burden
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; C002854:alovudine; D000068818:Cetuximab