Yujing Du1, Zhao Chen1, Xiaojiang Duan2, Ping Yan1, Chunli Zhang1, Lei Kang1, Rongfu Wang3,4. 1. Department of Nuclear Medicine, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing, 100034, China. 2. Department of Nuclear Medicine, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing, 100034, China. duanxj@pku.edu.cn. 3. Department of Nuclear Medicine, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing, 100034, China. rongfu_wang@163.com. 4. Department of Nuclear Medicine, Peking University International Hospital, 1 life Garden Road, Zhongguancun Life Science Park, Changping District, Beijing, 102206, China. rongfu_wang@163.com.
Abstract
OBJECTIVE: Pep-1 (CGEMGWVRC) can potently bind to interleukin 13 receptor α 2 (IL-13Rα2), a tumor-restricted receptor found to be expressed in various malignancies. In this study, we intended to prepare a 99mTc-labeled probe and evaluate its in vivo tumor accumulation properties in a cervical cancer xenograft model. METHODS: The Pep-1 was designed and radiolabeled with 99mTc by conjugation with mercaptoacetyl-triglycine (MAG3). The labeling yield, radiochemical purity and stability were characterized in vitro. Cell uptake assays and fluorescence imaging were conducted for qualitative and quantitative evaluation of the specificity and affinity of Pep-1. Flow cytometry and tissue immunofluorescence were used to confirm the IL-13Rα2 expression in cervical cancer. Biodistribution and in vivo imaging were performed periodically to evaluate the imaging value of 99mTc-MAG3-Pep-1 in cervical cancer xenograft model. RESULTS: 99mTc-MAG3-Pep-1 was successfully prepared with a high labeling yield and radiochemical purity (> 95%). Specific cell uptake was demonstrated by scramble control and unlabeled MAG3-Pep-1 blockade. Flow cytometry and tissue immunofluorescence also confirmed the mild IL-13Rα2 expression of HeLa. In the gamma imaging study and biodistribution, the tumors were imaged clearly at 2-6 h after injection of 99mTc-MAG3-Pep-1 and the accumulation of 99mTc-MAG3-Pep-1 in tumor was significantly higher than that in the blocking and scramble controls, demonstrating ligand-receptor binding specificity. CONCLUSIONS: This work demonstrated that 99mTc-MAG3-Pep-1 can bind to cervical cancer with high affinity and specificity. MAG3-Pep-1 may be a prospective precursor for IL-13Rα2-expressing cancer therapy.
OBJECTIVE: Pep-1 (CGEMGWVRC) can potently bind to interleukin 13 receptor α 2 (IL-13Rα2), a tumor-restricted receptor found to be expressed in various malignancies. In this study, we intended to prepare a 99mTc-labeled probe and evaluate its in vivo tumor accumulation properties in a cervical cancer xenograft model. METHODS: The Pep-1 was designed and radiolabeled with 99mTc by conjugation with mercaptoacetyl-triglycine (MAG3). The labeling yield, radiochemical purity and stability were characterized in vitro. Cell uptake assays and fluorescence imaging were conducted for qualitative and quantitative evaluation of the specificity and affinity of Pep-1. Flow cytometry and tissue immunofluorescence were used to confirm the IL-13Rα2 expression in cervical cancer. Biodistribution and in vivo imaging were performed periodically to evaluate the imaging value of 99mTc-MAG3-Pep-1 in cervical cancer xenograft model. RESULTS: 99mTc-MAG3-Pep-1 was successfully prepared with a high labeling yield and radiochemical purity (> 95%). Specific cell uptake was demonstrated by scramble control and unlabeled MAG3-Pep-1 blockade. Flow cytometry and tissue immunofluorescence also confirmed the mild IL-13Rα2 expression of HeLa. In the gamma imaging study and biodistribution, the tumors were imaged clearly at 2-6 h after injection of 99mTc-MAG3-Pep-1 and the accumulation of 99mTc-MAG3-Pep-1 in tumor was significantly higher than that in the blocking and scramble controls, demonstrating ligand-receptor binding specificity. CONCLUSIONS: This work demonstrated that 99mTc-MAG3-Pep-1 can bind to cervical cancer with high affinity and specificity. MAG3-Pep-1 may be a prospective precursor for IL-13Rα2-expressing cancer therapy.
Authors: Rodrigo Barderas; Rubén A Bartolomé; María Jesús Fernandez-Aceñero; Sofia Torres; J Ignacio Casal Journal: Cancer Res Date: 2012-04-13 Impact factor: 12.701
Authors: Sandeep Kunwar; Susan Chang; Manfred Westphal; Michael Vogelbaum; John Sampson; Gene Barnett; Mark Shaffrey; Zvi Ram; Joseph Piepmeier; Michael Prados; David Croteau; Christoph Pedain; Pamela Leland; Syed R Husain; Bharat H Joshi; Raj K Puri Journal: Neuro Oncol Date: 2010-02-04 Impact factor: 12.300