Bin-Bin Shih1, Yi-Fang Chang2, Chun-Chia Cheng2, Hao-Jhih Yang3, Kang-Wei Chang3, Ai-Sheng Ho1, Hua-Ching Lin4, Chun Yeh1, Chun-Chao Chang5. 1. Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan, ROC. 2. Hematology and Oncology, Mackay Memorial Hospital, Taipei, Taiwan, ROC. 3. Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan, ROC. 4. Division of Proctology, Cheng Hsin General Hospital, Taipei, Taiwan, ROC. 5. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan, ROC; Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC. Electronic address: chunchao@tmu.edu.tw.
Abstract
BACKGROUND: Epidermal growth factor receptor (EGFR) overexpressed in colorectal cancer (CRC) is a tumor target for developing the anti-tumor theranostic agents. Cetuximab, an anti-EGFR monoclonal antibody against EGFR-positive tumors, inhibits cell proliferation and growth was labeled with radioactive 111indium (111In) in this study for diagnosing EGFR-positive CRC. The aim of this study was to evaluate the efficacy of noninvasive nuclear imaging agent 111In-cetuximab and investigate the biological distribution of 111In-cetuximab in the HCT-15-induced EGFR-positive CRC tumor xenografts. METHODS: We conjugated cetuximab with an isotope chelator, diethylene triamine penta acetic acid (DTPA), and consequently labeled cetuximab-DTPA with 111In and measured the labeling efficacy by an instant thin layer chromatography (iTLC). Furthermore, the 111In-cetuximab was investigated and compared for imaging small (50 mm3) and large (250 mm3) tumor of CRC xenografts, respectively. RESULTS: The conjugated ratio between cetuximab and DTPA was 1:6 measured by MALDI-TOF-MS. The better labeling concentration of cetuximab with 10 mCi of 111In was calculated and experimented as 48 μg, resulting in labeling efficacy >80% detected by iTLC. The results revealed that the 111In-cetuximab accumulated in the both sizes of tumors as a reliable noninvasive diagnostic agent, whereas the ratio of tumor to muscle in the large tumor was 7.5-fold. The biodistribution data indicated that the 111In-cetuximab bound to tumor specifically that was higher than that in other organs. CONCLUSION: We suggested that the 111In-cetuximab was potential for early diagnosis and prognostic monitor of EGFR-positive CRC in further clinical practice.
BACKGROUND:Epidermal growth factor receptor (EGFR) overexpressed in colorectal cancer (CRC) is a tumor target for developing the anti-tumor theranostic agents. Cetuximab, an anti-EGFR monoclonal antibody against EGFR-positive tumors, inhibits cell proliferation and growth was labeled with radioactive 111indium (111In) in this study for diagnosing EGFR-positive CRC. The aim of this study was to evaluate the efficacy of noninvasive nuclear imaging agent 111In-cetuximab and investigate the biological distribution of 111In-cetuximab in the HCT-15-induced EGFR-positive CRC tumor xenografts. METHODS: We conjugated cetuximab with an isotope chelator, diethylene triamine penta acetic acid (DTPA), and consequently labeled cetuximab-DTPA with 111In and measured the labeling efficacy by an instant thin layer chromatography (iTLC). Furthermore, the 111In-cetuximab was investigated and compared for imaging small (50 mm3) and large (250 mm3) tumor of CRC xenografts, respectively. RESULTS: The conjugated ratio between cetuximab and DTPA was 1:6 measured by MALDI-TOF-MS. The better labeling concentration of cetuximab with 10 mCi of 111In was calculated and experimented as 48 μg, resulting in labeling efficacy >80% detected by iTLC. The results revealed that the 111In-cetuximab accumulated in the both sizes of tumors as a reliable noninvasive diagnostic agent, whereas the ratio of tumor to muscle in the large tumor was 7.5-fold. The biodistribution data indicated that the 111In-cetuximab bound to tumor specifically that was higher than that in other organs. CONCLUSION: We suggested that the 111In-cetuximab was potential for early diagnosis and prognostic monitor of EGFR-positive CRC in further clinical practice.
Authors: Raquel Benedetto; Adriana V F Massicano; Bryant K Crenshaw; Renato Oliveira; Rui M Reis; Elaine B Araújo; Suzanne E Lapi Journal: Cancer Biother Radiopharm Date: 2019-03-13 Impact factor: 3.099
Authors: Dominik Witzigmann; Philipp Uhl; Sandro Sieber; Christina Kaufman; Tomaz Einfalt; Katrin Schöneweis; Philip Grossen; Jonas Buck; Yi Ni; Susanne H Schenk; Janine Hussner; Henriette E Meyer Zu Schwabedissen; Gabriela Québatte; Walter Mier; Stephan Urban; Jörg Huwyler Journal: Elife Date: 2019-07-23 Impact factor: 8.140