論文 - 詳細
RRC ID | 66891 |
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著者 | Song IH, Jeong MS, Hong HJ, Shin JI, Park YS, Woo SK, Moon BS, Kim KI, Lee YJ, Kang JH, Lee TS. |
タイトル | Development of a Theranostic Convergence Bioradiopharmaceutical for Immuno-PET Based Radioimmunotherapy of L1CAM in Cholangiocarcinoma Model. |
ジャーナル | Clin Cancer Res |
Abstract |
PURPOSE:Cholangiocarcinoma is a malignancy of bile duct with a poor prognosis. Conventional chemotherapy and radiotherapy are generally ineffective, and surgical resection is the only curative treatment for cholangiocarcinoma. L1-cell adhesion molecule (L1CAM) has been known as a novel prognostic marker and therapeutic target for cholangiocarcinoma. This study aimed to evaluate the feasibility of immuno-PET imaging-based radioimmunotherapy using radiolabeled anti-L1CAM antibody in cholangiocarcinoma xenograft model. EXPERIMENTAL DESIGN:We prepared a theranostic convergence bioradiopharmaceutical using chimeric anti-L1CAM antibody (cA10-A3) conjugated with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator and labeled with 64Cu or 177Lu and evaluated the immuno-PET or SPECT/CT imaging and biodistribution with 64Cu-/177Lu-cA10-A3 in various cholangiocarcinoma xenograft models. Therapeutic efficacy and response monitoring were performed by 177Lu-cA10-A3 and 18F-FDG-PET, respectively, and immunohistochemistry was done by TUNEL and Ki-67. RESULTS:Radiolabeled cA10-A3 antibodies specifically recognized L1CAM in vitro, clearly visualized cholangiocarcinoma tumors in immuno-PET and SPECT/CT imaging, and differentiated the L1CAM expression level in cholangiocarcinoma xenograft models. 177Lu-cA10-A3 (12.95 MBq/100 μg) showed statistically significant reduction in tumor volumes (P < 0.05) and decreased glucose metabolism (P < 0.01). IHC analysis revealed 177Lu-cA10-A3 treatment increased TUNEL-positive and decreased Ki-67-positive cells, compared with saline, cA10-A3, or 177Lu-isotype. CONCLUSIONS:Anti-L1CAM immuno-PET imaging using 64Cu-cA10-A3 could be translated into the clinic for characterizing the pharmacokinetics and selecting appropriate patients for radioimmunotherapy. Radioimmunotherapy using 177Lu-cA10-A3 may provide survival benefit in L1CAM-expressing cholangiocarcinoma tumor. Theranostic convergence bioradiopharmaceutical strategy would be applied as imaging biomarker-based personalized medicine in L1CAM-expressing patients with cholangiocarcinoma. |
巻・号 | 25(20) |
ページ | 6148-6159 |
公開日 | 2019-10-15 |
DOI | 10.1158/1078-0432.CCR-19-1157 |
PII | 1078-0432.CCR-19-1157 |
PMID | 31337646 |
MeSH | Animals Bile Duct Neoplasms / diagnostic imaging Bile Duct Neoplasms / immunology Bile Duct Neoplasms / pathology Bile Duct Neoplasms / radiotherapy* Bile Ducts / diagnostic imaging Bile Ducts / pathology Cell Line, Tumor Cholangiocarcinoma / diagnostic imaging Cholangiocarcinoma / immunology Cholangiocarcinoma / pathology Cholangiocarcinoma / radiotherapy* Female Heterocyclic Compounds, 1-Ring / administration & dosage Heterocyclic Compounds, 1-Ring / chemistry Heterocyclic Compounds, 1-Ring / pharmacokinetics Humans Immunoconjugates / administration & dosage Immunoconjugates / chemistry Immunoconjugates / pharmacokinetics Mice Neural Cell Adhesion Molecule L1 / antagonists & inhibitors* Neural Cell Adhesion Molecule L1 / immunology Positron-Emission Tomography Radioimmunotherapy / methods* Radiopharmaceuticals / administration & dosage* Radiopharmaceuticals / chemistry Radiopharmaceuticals / pharmacokinetics Theranostic Nanomedicine / methods Tissue Distribution Tomography, Emission-Computed, Single-Photon Xenograft Model Antitumor Assays |
IF | 10.107 |
リソース情報 | |
ヒト・動物細胞 | TFK-1(RCB2537) |