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Abstract
Purpose
The humanized monoclonal antibody hR3, both alone and in combination with other chemotherapeutic agents and radiotherapy, can be used to treat head and neck cancers. Substantial progress has been made in the development of targeted radioimmunotherapy using iodine-131 (131I) and yttrium-90 (90Y) radioisotopes in recent years. In the present study, we examined the efficacy of hR3 conjugated with 131I or 90Y to inhibit tumor growth in a laryngeal carcinoma xenograft tumor model.
Methods
hR3 was labeled with 131I or 90Y to generate the conjugates 131I-hR3 or 90Y-hR3. The conjugates were incubated with HEp-2 laryngeal carcinoma cells to evaluate binding capacity. The efficacy of the labeled hR3 conjugates to treat laryngeal cancer was also evaluated in nude mice inoculated with HEp-2 tumors.
Results
The purified radioimmunoconjugates with specific activities of 187–191 MBq/mg had radiochemical purity >98% and >80% immunoreactivity with HEp-2 cells. Mice with HEp-2 xenografts treated with 131I-hR3 or 90Y-hR3 showed reduced tumor volume and improved survival rates compared to the untreated control group and the group treated with unlabeled hR3. At equivalent doses, radioimmunotherapeutic hR3 labeled with 90Y had increased tumor inhibition activity compared to hR3 labeled with 131I.
Conclusions
131I-hR3 and 90Y-hR3 are promising targeted radiopharmaceuticals for treatment of head and neck cancers, especially laryngeal cancers.
Acknowledgment
We thank Dr. Marco Chinol (European Institute of Oncology, Milan, Italy) for supervising the experiments and for providing valuable comments and discussion throughout the project.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Notes on contributors
Thi-Thu Nguyen
Thi-Thu Nguyen has a Doctor of Philosophy in Biology. Her research interests include strategic management in the developed production of radioisotopes and radiopharmaceuticals. The related scientific experiences are production of radiopharmaceuticals such as 99mTc-DMSA, 99mTc-DTPA, 99mTc-MDP, 99mTc-phytec, 131I-Hippuran for local uses in Vietnam; Preparation in-house 90Sr/90Y generator using supported liquid membrane technology and develop the therapeutic radiopharmaceuticals for cancer treatments. These are 90Y-rituximab/131I-rituximab directed again CD20+ Non Hodgkin Lymphoma, 90Y-nimotuzumab/131I-nimotuzumab again EGFR for the treatment of head and neck cancer, 90Y-anti CD25 antibody directed again Hodgkin Lymphoma; Participated 2 national scientific projects, and principle investigator of a national scientific project on the radiolabeling of nimotuzumab with radioisotope 131I, 90Y for head and neck cancer therapy; Chief scientific investigator of IAEA Coordinated Research Project Preclinical evaluation of peptides and antibodies radiopharmaceuticals labeled with generator produced 90Y for potential clinical use.
Anh-Son Ho
Anh-Son Ho is an Associate Professor and has been the faculty at the Department of Pathophysiology and the Institute of Biomedicine and Pharmacy, Vietnam Military Medical University. His current research interests in the areas of investigation of the function of areas in the brain, measure biological compatibility and effects of biological products in animal models of diseases: Alzheimer, stroke, autism, hypertension, diabetes, arthritis and obesity; Pathogenesis of diseases such as cancers and infectious diseases as well as the molecular epidemiology of infectious pathogens: Developing several animal models for pathophysiological studies to testing the oncolytic therapy (Measle and Mump virus vaccine) in vitro and in vivo.
Thi-Khanh-Giang Nguyen
Thi-Khanh-Giang Nguyen has a Master of Science degree in Biology. She is responsible for the production of radiopharmaceuticals, such as lyophilization kits for labelling with 99mTc, radiolabeled biomolecules. She works at the Center for Research and Production of Radioisotopes, Nuclear Research Institute.
Thi-Ngoc Nguyen
Thi-Ngoc Nguyen has a Master of Science degree in Biology. She is responsible for the production of radiopharmaceuticals such as lyophilization kits for labelling with 99mTc, radiolabeled biomolecules. She performs the quality controls of radiopharmaceuticals. She works at the Center for Research and Production of Radioisotopes, Nuclear Research Institute.
Van-Cuong Bui
Van-Cuong Bui is the Head of Center for Research and Production of Radioisotopes, Nuclear Research Institute. He has his B.S in radiochemistry. He has experience in the production of 99mTc generators and radioisotopes such as 131I, 90Y, 99mTc, 32P, 177Lu, 166Ho for medical use.
Thanh-Binh Nguyen
Thanh-Binh Nguyen has a BS degree in radiochemistry. He works at the Center for Research and Production of Radioisotopes, Nuclear Research Institute. He has experience in the production of radioisotopes and radiopharmaceuticals. He is responsible for the production of 32P in the forms of solution and application.
Ho-Hong-Quang Dang
Ho-Hong-Quang Dang received his BS degree in chemistry science. He works at the Center for Research and Production of Radioisotopes, Nuclear Research Institute. He is responsible for the production of 131I capsules. He is interest in the radiolabeling small molecular.
Dang-Khoa Nguyen
Dang-Khoa Nguyen is obtained a BS degree in Biology at the Dalat University. He works at the Center for Research and Production of Radioisotopes, Nuclear Research Institute. He has experience in the production of 99mTc generators and quality of radiopharmaceuticals for medical purposes.
Thanh-Nhan Nguyen
Thanh-Nhan Nguyen received his MD in chemistry science at the Dalat University. He works at the Center for Research and Production of Radioisotopes, Nuclear Research Institute. He is interested in the radiolabeling and quality control of radiopharmaceuticals.
Linh-Toan Nguyen
Linh-Toan Nguyen is the Professor of Pathophysiology at the Department of Pathophysiology and the Institute of Biomedicine and Pharmacy, Vietnam Military Medical University. He is a leader of the research group which has gained experiences on studying the pathogenesis of diseases such as cancers and infectious diseases as well as the molecular epidemiology of infectious pathogens (hepatitis viruses, Dengue virus, B19 and Malaria), the molecular biology studies that involved to the liver disease with HBV infection. There were also few studies that involve both mutated HBV genes and variants of host genes associated to the liver disease with HBV infection. In addition, the research group has focused on the polymorphisms of several immunological genes on HBV infections and outcome. Recently, the research group has focused on the investigation of sMICA and sMICB serum levels in patients infected with hepatitis B, liver cirrhosis and HBV-related liver cancer, analysed the clinical correlation of sMICA and sMICB serum levels with clinical characteristics and clinical parameters in patients with chronic hepatitis B, liver cirrhosis and HBV-related HCC. Importantly, the research group focuses on establishing and developing several animal models for pathophysiological studies such as animal models for cancers (liver, colorectal, lung, ovary cancers etc.) as well as for other diseases including obesity. Based on the developed animal models for cancers, the research group has utilized oncolytic viruses (OLVs) including measles and mumps viruses (MeV and MuV), which have a great potential to serve as a therapeutic option for cancers, to examine their anticancer effects on hematopoietic cancer cell lines as well as human solid malignancies. The research group also used Oncolytic viruses in combination with monoclonal antibodies (Nimotuzumab) to treat laryngeal cancer in vitro and in vivo. Recently, the research group has conducted several studies related to diabetes type 2. In this aspect, the research group determined and analyzed a number of adipokines and pro-inflammatory cytokines and their association with clinical outcome of diabetes type 2 in Vietnamese patients with and without overweight.