A Fluorescent, [18F]-Positron-Emitting Agent for Imaging Prostate-Specific Membrane Antigen Allows Genetic Reporting in Adoptively Transferred, Genetically Modified Cells

被引:13
作者
Guo, Hua [1 ]
Kommidi, Harikrishna [1 ]
Vedvyas, Yogindra [1 ]
McCloskey, Jaclyn E. [1 ]
Zhang, Weiqi [1 ]
Chen, Nandi [1 ,2 ]
Nurili, Fuad [3 ]
Wu, Amy P. [4 ]
Sayman, Haluk B. [5 ]
Akin, Oguz [3 ]
Rodriguez, Erik A. [6 ]
Aras, Omer [3 ]
Jin, Moonsoo M. [1 ]
Ting, Richard [1 ]
机构
[1] Weill Cornell Med Coll, MI3, Dept Radiol, New York, NY 10065 USA
[2] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Gastrointestinal Surg, Shenzhen 518020, Guangdong, Peoples R China
[3] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA
[4] Hofstra Northwell Sch Med, Dept Otolaryngol Head & Neck Surg, Northwell Hlth, Hempstead, NY 11549 USA
[5] Istanbul Univ Cerrahpasa, Cerrahpasa Med Fac, Dept Nucl Med, TR-34303 Istanbul, Turkey
[6] George Washington Univ, Dept Chem, Washington, DC 20052 USA
基金
美国国家卫生研究院;
关键词
REAL-TIME; GUIDED SURGERY; CANCER; EXPRESSION; INTERNALIZATION; HALOTAG; MODEL;
D O I
10.1021/acschembio.9b00160
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Clinical trials involving genome-edited cells are growing in popularity, where CAR-T immunotherapy and CRISPR/Cas9 editing are more recognized strategies. Genetic reporters are needed to localize the molecular events inside these cells in patients. Specifically, a nonimmunogenic genetic reporter is urgently needed as current reporters are immunogenic due to derivation from nonhuman sources. Prostate-specific membrane antigen (PSMA) is potentially nonimmunogenic due to its natural, low-level expression in select tissues (self-MHC display). PSMA overexpression on human prostate adenocarcinoma is also visible with excellent contrast. We exploit these properties in a transduced, two component, Human-Derived, Genetic, Positron-emitting, and Fluorescent (HD-GPF) reporter system. Mechanistically analogous to the luciferase and luciferin reporter, PSMA is genetically encoded into non-PSMA expressing 8505C cells and tracked with ACUPA-Cy3-BF3, a single, systemically injected small molecule that delivers positron emitting fluoride (F-18) and a fluorophore (Cy3) to report on cells expressing PSMA. PSMA-lentivirus transduced tissues become visible by Cy3 fluorescence,[F-18]-positron emission tomography (PET), and gamma-scintillated biodistribution. HD-GPF fluorescence is visible at subcellular resolution, while a reduced PET background is achieved in vivo, due to rapid ACUPA-Cy3-BF3 renal excretion. Co-transduction with luciferase and GFP show specific advantages over popular genetic reporters in advanced murine models including, a "mosaic" model of solid-tumor intratumoral heterogeneity and a survival model for observing postsurgical recurrence. We report an advanced genetic reporter that tracks genetically modified cells in entire animals and with subcellular resolution with PET and fluorescence, respectively. This reporter system is potentially nonimmunogenic and will therefore be useful in human studies. PSMA is a biomarker of prostate adenocarcinoma and ACUPA-Cy3-BF3 potential in radical prostatectomy is demonstrated.
引用
收藏
页码:1449 / 1459
页数:11
相关论文
共 47 条
[1]   Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer [J].
Afshar-Oromieh, Ali ;
Zechmann, Christian M. ;
Malcher, Anna ;
Eder, Matthias ;
Eisenhut, Michael ;
Linhart, Heinz G. ;
Holland-Letz, Tim ;
Hadaschik, Boris A. ;
Giesel, Frederik L. ;
Debus, Juergen ;
Haberkorn, Uwe .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2014, 41 (01) :11-20
[2]   Quantum dot - Aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on Bi-fluorescence resonance energy transfer [J].
Bagalkot, Vaishali ;
Zhang, Liangfang ;
Levy-Nissenbaum, Etgar ;
Jon, Sangyong ;
Kantoff, Philip W. ;
Langer, Robert ;
Farokhzad, Omid C. .
NANO LETTERS, 2007, 7 (10) :3065-3070
[3]   PSMA-targeted contrast agents for intraoperative imaging of prostate cancer [J].
Bao, Kai ;
Lee, Jeong Heon ;
Kang, Homan ;
Park, G. Kate ;
El Fakhri, Georges ;
Choi, Hak Soo .
CHEMICAL COMMUNICATIONS, 2017, 53 (10) :1611-1614
[4]   PSMA-11-Derived Dual-Labeled PSMA Inhibitors for Preoperative PET Imaging and Precise Fluorescence-Guided Surgery of Prostate Cancer [J].
Baranski, Ann-Christin ;
Schaefer, Martin ;
Bauder-Wuest, Ulrike ;
Roscher, Mareike ;
Schmidt, Jana ;
Stenau, Esther ;
Simpfendoerfer, Tobias ;
Teber, Dogu ;
Maier-Hein, Lena ;
Hadaschik, Boris ;
Haberkorn, Uwe ;
Eder, Matthias ;
Kopka, Klaus .
JOURNAL OF NUCLEAR MEDICINE, 2018, 59 (04) :639-645
[5]   PSMA expression: a potential ally for the pathologist in prostate cancer diagnosis [J].
Bravaccini, Sara ;
Puccetti, Maurizio ;
Bocchini, Martine ;
Ravaioli, Sara ;
Celli, Monica ;
Scarpi, Emanuela ;
De Giorgi, Ugo ;
Tumedei, Maria Maddalena ;
Raulli, Giandomenico ;
Cardinale, Loredana ;
Paganelli, Giovanni .
SCIENTIFIC REPORTS, 2018, 8
[6]   Evaluation of Prostate-Specific Membrane Antigen as an Imaging Reporter [J].
Castanares, Mark A. ;
Mukherjee, Amarnath ;
Chowdhury, Wasim H. ;
Liu, Minzhi ;
Chen, Ying ;
Mease, Ronnie C. ;
Wang, Yuchuan ;
Rodriguez, Ronald ;
Lupold, Shawn E. ;
Pomper, Martin G. .
JOURNAL OF NUCLEAR MEDICINE, 2014, 55 (05) :805-811
[7]   A low molecular weight PSMA-based fluorescent imaging agent for cancer [J].
Chen, Ying ;
Dhara, Surajit ;
Banerjee, Sangeeta Ray ;
Byun, Youngjoo ;
Pullambhatla, Mrudula ;
Mease, Ronnie C. ;
Pomper, Martin G. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 390 (03) :624-629
[8]   Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase [J].
Davis, MI ;
Bennett, MJ ;
Thomas, LM ;
Bjorkman, PJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (17) :5981-5986
[9]   Molecular analysis of a congenital iodide transport defect:: G543E impairs maturation and trafficking of the Na+/I- symporter [J].
De la Vieja, A ;
Ginter, CS ;
Carrasco, N .
MOLECULAR ENDOCRINOLOGY, 2005, 19 (11) :2847-2858
[10]   68Ga-Complex Lipophilicity and the Targeting Property of a Urea-Based PSMA Inhibitor for PET Imaging [J].
Eder, Matthias ;
Schaefer, Martin ;
Bauder-Wuest, Ulrike ;
Hull, William-Edmund ;
Waengler, Carmen ;
Mier, Walter ;
Haberkorn, Uwe ;
Eisenhut, Michael .
BIOCONJUGATE CHEMISTRY, 2012, 23 (04) :688-697