Original Paper

Apoptosis

, Volume 18, Issue 2, pp 238-247

An in vivo molecular imaging probe 18F-Annexin B1 for apoptosis detection by PET/CT: preparation and preliminary evaluation

  • Ming-Wei WangAffiliated withPET Center, Department of Nuclear Medicine, Fudan University Shanghai Cancer CenterDepartment of Oncology, Shanghai Medical College, Fudan UniversityThe Joint Center for Biomedical Imaging of Department of Chemistry & Institute of Biomedical Science & Shanghai Cancer Center, Fudan University
  • , Fang WangAffiliated withDepartment of Medical Genetics, Second Military Medical University (SMMU)
  • , Yu-Jia ZhengAffiliated withPET Center, Department of Nuclear Medicine, Fudan University Shanghai Cancer CenterDepartment of Oncology, Shanghai Medical College, Fudan UniversityThe Joint Center for Biomedical Imaging of Department of Chemistry & Institute of Biomedical Science & Shanghai Cancer Center, Fudan University
  • , Ying-Jian ZhangAffiliated withPET Center, Department of Nuclear Medicine, Fudan University Shanghai Cancer CenterDepartment of Oncology, Shanghai Medical College, Fudan UniversityThe Joint Center for Biomedical Imaging of Department of Chemistry & Institute of Biomedical Science & Shanghai Cancer Center, Fudan University Email author 
  • , Yong-Ping ZhangAffiliated withPET Center, Department of Nuclear Medicine, Fudan University Shanghai Cancer CenterDepartment of Oncology, Shanghai Medical College, Fudan UniversityThe Joint Center for Biomedical Imaging of Department of Chemistry & Institute of Biomedical Science & Shanghai Cancer Center, Fudan University
  • , Qing ZhaoAffiliated withPET Center, Department of Nuclear Medicine, Fudan University Shanghai Cancer CenterDepartment of Oncology, Shanghai Medical College, Fudan University
  • , Clifton Kwang-Fu ShenAffiliated withDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California Los Angeles (UCLA)Crump Institute for Molecular Imaging (CIMI), David Geffen School of Medicine at University of California Los Angeles (UCLA)California NanoSystems Institute (CNSI), University of California Los Angeles (UCLA)
  • , Yue WangAffiliated withDepartment of Medical Genetics, Second Military Medical University (SMMU)
  • , Shu-Han SunAffiliated withDepartment of Medical Genetics, Second Military Medical University (SMMU) Email author 

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Abstract

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.

Keywords

Apoptosis imaging 18F-Annexin B1 18F-radiolabeling Molecular imaging probe PET