Development of Gold Nanorods Conjugated with Radiolabeled Anti-human Epidermal Growth Factor Receptor 2 (HER2) Monoclonal Antibody as Single-Photon Emission Computed Tomography/Photoacoustic Dual-Imaging Probes Targeting HER2-Positive Tumors
Autor: | Masahiro Ono, Hideo Saji, Yoichi Shimizu, Hiroyuki Watanabe, Ning Ding, Takeshi Namita, Kohei Sano, Tsuyoshi Shiina |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Biodistribution Receptor ErbB-2 medicine.drug_class Mice Nude Pharmaceutical Science Single-photon emission computed tomography Monoclonal antibody Photoacoustic Techniques Mice 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Nuclear magnetic resonance Drug Development Trastuzumab In vivo Cell Line Tumor Neoplasms Spect imaging medicine Animals Humans Epidermal growth factor receptor Tomography Emission-Computed Single-Photon Pharmacology Mice Inbred BALB C Nanotubes medicine.diagnostic_test biology Chemistry Antibodies Monoclonal General Medicine In vitro 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Female Gold Protein Binding medicine.drug |
Zdroj: | Biological and Pharmaceutical Bulletin. 43:1859-1866 |
ISSN: | 1347-5215 0918-6158 |
Popis: | Surgery remains one of the main treatments of cancer and both precise pre- and intraoperative diagnoses are crucial in order to guide the operation. We consider that using an identical probe for both pre- and intra-operative diagnoses would bridge the gap between surgical planning and image-guided resection. Therefore, in this study, we developed gold nanorods (AuNRs) conjugated with radiolabeled anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, and investigated their feasibility as novel HER2-targeted dual-imaging probes for both single photon emission computed tomography (SPECT) (preoperative diagnosis) and photoacoustic (PA) imaging (intraoperative diagnosis). To achieve the purpose, AuNRs conjugated with different amount of trastuzumab (Tra) were prepared, and Tra-AuNRs were labeled with indium-111. After the evaluation of binding affinity to HER2, cell binding assay and biodistribution studies were carried out for optimization. AuNRs with moderate trastuzumab conjugation (Tra2-AuNRs) were proposed as the novel probe and demonstrated significantly higher accumulation in NCI-N87 (HER2 high-expression) tumors than in SUIT2 (low-expression) tumors 96 h post-injection along with good affinity towards HER2. Thereafter, in vitro PA imaging and in vivo SPECT imaging studies were performed. In in vitro PA imaging, Tra2-AuNRs-treated N87 cells exhibited significant PA signal increase than SUIT2 cells. In in vivo SPECT, signal increase in N87 tumors was more notable than that in SUIT2 tumors. Herein, we report that the Tra2-AuNRs enabled HER2-specific imaging, suggesting the potential as a robust HER2-targeted SPECT and PA dual-imaging probe. |
Databáze: | OpenAIRE |
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