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153Sm-DTPA-Cetuximab targeted to tumors xenografted in mice

Other Titles
 마우스 종양 모델에서 153Sm-DTPA-Cetuximab의 암세포 표적 및 항암 활성 분석 
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Dept. of Biomedical Laboratory Science/석사
The radionuclide labeled with monoclonal antibodies can be delivered to the target cells and showed successful results in cancer, which is known as radioimmunotherapy (RIT). 153Sm (T1/2; 46.3 hr) is a medium beta energy emitter [Emax = 810 (20%), 710 (50%) and 640 (30%) keV] with 30% abundance of gamma emission (103 keV) that is suitable for radioimmunoscintigraphy and radioimmunotherapy. In addition to the desirable emission properties of 153Sm, it also readily forms complexes with bifunctional chelating agents that can be conjugated to antibodies. Cetuximab, a chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), is currently used to treat several solid tumors. In this study, 153Sm-Diethylene triamine pentaacetic acid (DTPA)-Cetuximab was assessed by immuno-single photon emission computed tomography (immuno-SPECT) imaging and RIT as a potential diagnostic and therapy application in a EGFR expression tumor (A431) model. The antibody was labeled with 153Sm-chloride after conjugation with freshly prepared DTPA and their immunoreactivity exceeded 71% for A431 tumor. The in vitro stability test of 153Sm-DTPA-Cetuximab in serum indicated that >96% of the radionuclide remained bound to the antibody for 24 hr. The biodistribution study using 153Sm-DTPA-Cetuximab indicated the highest tumor uptake of 10.65 ± 0.66% ID/g at 120 hr post-injection and tumor-to-blood and tumor-to-muscle ratios of 4.83 ± 1.41 and 21.43 ± 4.54% ID/g at 168 hr post-injection, respectively. This data shows that the urinary system is a predominant clearance system for the 153Sm-DTPA-Cetuximab. A quantitative analysis was also performed using SPECT/CT and autoradiography images. 153Sm-DTPA-Cetuximab was selectively localized in EGFR-positive A431 tumors. The RIT efficacy of 153Sm-DTPA-Cetuximab was evaluated once a week for 4 week in A431-xenografted mice. RIT with 153Sm-DTPA-Cetuximab resulted in delayed tumor growth. The biodistribution, SPECT/CT and autoradiography results suggest that 153Sm-DTPA-Cetuximab can be applicable for in vivo diagnosis of cancers and RIT with 153Sm-DTPA-Cetuximab is effective in inhibition of EGFR-expressing tumors with acceptable toxicity.
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