[1]Fudan University, Center for Biomedical Imaging,Shanghai,China
[2]Huazhong University of Science and Technology, Department of Pharmacology,Wuhan,China
[3]Shanghai University, Department of Nuclear Medicine,Shanghai,China
[4]Fudan University Shanghai Medical College, Department of Oncology,Shanghai,China
[5]Shanghai Jiao Tong University School of Medicine, Department of Gastroenterology,Shanghai,China
[6]China-Japan Union Hospital, Department of Neurology,Changchun,China
[7]David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology,Los Angeles,United States
[8]Second Military Medical University, Research Center of Developmental Biology,Shanghai,China
[9]Second Military Medical University, Department of Medical Genetics,Shanghai,China
There is an increasing need to develop non-invasive molecular imaging strategies for visualizing and quantifying apoptosis status of diseases (especially for cancer) for diagnosis and monitoring treatment response. Since externalization of phosphatidylserine (PS) is one of the early molecular events during apoptosis, Annexin B1 (AnxB1), a member of Annexins family with high affinity toward the head group of PS, could be a potential positron emission tomography (PET) imaging probe for imaging cell death process after labeled by positron-emitting nuclides, such as 18F. In the present study, we investigated a novel PET probe, 18F-labeled Annexin B1 ( 18F-AnxB1), for apoptosis imaging. 18F-AnxB1 was prepared reliably by conjugating AnxB1 with a 18F-tag, N-succinimidyl 4-[ 18F]fluorobenzoate ([18F]SFB), in a radiolabeling yield of about 20 % within 40 min. The in vitro binding of 18F-AnxB1 with apoptotic cells induced by anti-Fas antibody showed twofold increase compared to those without treatment, confirmed by flow cytometric analysis with AnxV-FITC/PI staining. Stability tests demonstrated 18F-AnxB1 was rather stable in vitro and in vivo without degradation. The serial 18F-AnxB1 PET/CT scans in healthy rats outlined its biodistribution and pharmacokinetics, indicating a rapid renal clearance and predominant accumulation into kidney and bladder at 2 h p.i. 18F-AnxB1 PET/CT imaging was successfully applied to visualize in vivo apoptosis sites in tumor induced by chemotherapy and in kidney simulated by ischemia-reperfusion injury. The high-contrast images were obtained at 2 h p.i. to delineate apoptotic tumor. Apoptotic region could be still identified by 18F-AnxB1 PET 4 h p.i., despite the high probe retention in kidneys. In summary, we have developed 18F-AnxB1 as a PS-specific PET probe for the apoptosis detection and quantification which could have broad applications from disease diagnosis to treatment monitoring, especially in the cases of cancer. © 2012 Springer Science+Business Media New York.
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