RRC ID 66891
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)