論文 - 詳細
| RRC ID | 62767 |
|---|---|
| 著者 | Song IH, Lee TS, Park YS, Lee JS, Lee BC, Moon BS, An GI, Lee HW, Kim KI, Lee YJ, Kang JH, Lim SM. |
| タイトル | Immuno-PET Imaging and Radioimmunotherapy of 64Cu-/177Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model. |
| ジャーナル | J Nucl Med |
| Abstract |
UNLABELLED:Immuno-PET provides valuable information about tumor location, phenotype, susceptibility to therapy, and treatment response, especially to targeted radioimmunotherapy. In this study, we prepared antiepidermal growth factor receptor (EGFR) antibody via identical chelator, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-trience-3,6,9,-triacetic acid (PCTA), labeled with (64)Cu or (177)Lu to evaluate the EGFR expression levels using immuno-PET and the feasibility of radioimmunotherapy in an esophageal squamous cell carcinoma (ESCC) model. METHODS:Cetuximab was conjugated with p-SCN-Bn-PCTA and radiolabeled with (64)Cu or (177)Lu. In vitro EGFR expression levels were determined and compared using flow cytometry and cell binding assay. In vivo EGFR expression levels were evaluated via immuno-PET imaging of (64)Cu-cetuximab and biodistribution analysis. Micro-SPECT/CT imaging, biodistribution, and radioimmunotherapy studies of (177)Lu-cetuximab were performed in the ESCC model. Therapeutic responses were monitored using (18)F-FDG PET and immunohistochemical staining. RESULTS:(64)Cu- or (177)Lu-labeled antibodies showed high radiolabeling yield (>98%), stability (>90%), and favorable immunoreactivity. In vitro EGFR status measured by cell binding assay was correlated with the flow cytometry data. Immuno-PET, micro-SPECT/CT, and biodistribution demonstrated specific uptake in ESCC tumors depending on the EGFR expression levels. Tumor accumulation of (64)Cu- and (177)Lu-cetuximab was peaked at 48 and 120 h, respectively. Radioimmunotherapy with (177)Lu-cetuximab showed significant inhibition of tumor growth (P < 0.01) and marked reduction of (18)F-FDG SUV compared with that of control (P < 0.05). Terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity and Ki-67 staining indices increased and decreased, respectively, in the radioimmunotherapy group compared with other groups (P < 0.01). CONCLUSION:(64)Cu-cetuximab immuno-PET represented EGFR expression levels in ESCC tumors, and (177)Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth. The diagnostic and therapeutic convergence radiopharmaceutical (64)Cu-/(177)Lu-PCTA-cetuximab may be useful as a diagnostic tool in patient selection and a potent radioimmunotherapy agent in EGFR-positive ESCC tumors. |
| 巻・号 | 57(7) |
| ページ | 1105-11 |
| 公開日 | 2016-7-1 |
| DOI | 10.2967/jnumed.115.167155 |
| PII | jnumed.115.167155 |
| PMID | 26917708 |
| MeSH | Antineoplastic Agents / therapeutic use Carcinoma, Squamous Cell / diagnostic imaging* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / radiotherapy* Cell Line, Tumor Cetuximab / therapeutic use Chelating Agents / chemistry Copper Radioisotopes* ErbB Receptors / biosynthesis ErbB Receptors / immunology* Esophageal Neoplasms / diagnostic imaging* Esophageal Neoplasms / metabolism Esophageal Neoplasms / radiotherapy* Humans In Situ Nick-End Labeling Lutetium* Positron Emission Tomography Computed Tomography / methods* Radioimmunotherapy / methods* Radiopharmaceuticals / therapeutic use Tissue Distribution Tomography, Emission-Computed, Single-Photon Whole Body Imaging |
| IF | 7.887 |
| リソース情報 | |
| ヒト・動物細胞 | TE-1(RCB1894) TE-4(RCB2097) TE-5(RCB1949) TE-8(RCB2098) |