Availability: In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma

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Bibliographic Details
Main Author:	Schmitt, Julia (Author)
Format:	Thesis/Dissertation Book
Language:	English
Published:	Tübingen 2015
Subjects:	Hochschulschrift
Links:	http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029065125&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
Physical Description:	XIII, 171 Seiten Illustrationen, Diagramme

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adam_text	IN VITRO AND IN VIVO CHARACTERIZATION OF ANTIBODY BASED PET TRACERS FOR IMAGING OF NEUROBLASTOMA DISSERTATION DER M ATHEM ATISCH-N ATURW ISSENSCHAFTLICHEN FAKULTAT DER EBERHARD KARLS UNIVERSITAET TUEBINGEN ZUR ERLANGUNG DES G RADES EINES DOKTORS DER N A T_ IS S E N S C H A FTE N (DR. RER. NAT.) VORGELEGT VON JULIA SCHM ITT AUS O FFENBACH AM MAIN TUEBINGEN 2 0 1 5 TABLE OF CONTENTS 1 INTRODUCTION............................................................................................................................... 1 1.1 THE NEUROBLASTOMA.........................................................................................................1 1.2 DEVELOPMENT................................................................................................................... 2 1.3 DIAGNOSIS...........................................................................................................................3 1.4 IMAGING BASED DIAGNOSIS.............................................................................................. 6 1.4.1 NOVEL IMAGING STRATEGIES - PET T RA C E R.............................................................9 1.5 THERAPY...........................................................................................................................11 1.5 * STATE OF THE A RT.......................................................................................................11 1.5.2 IMMUNOTHERAPY.....................................................................................................12 1.6 ANTIBODIES IN NUCLEAR MEDICINE..................................................................................18 1.7 RADIOLABELING................................................................................................................. 21 1.7.1 C * PPE * -6 4 ..............................................................................................................21 1.7.2 BJFUNCTIONAL CHELATORS.........................................................................................22 1.8 IMAGING M ODALITIES........................................................................................................ 25 1.8.1 COMPUTED TOMOGRAPHY ...................................................................................... 25 1.8.2 MAGNETIC RESONANCE IMAGING............................................................................ 25 1.8.3 MOLECULAR IMAGING................................................................................................ 28 2 PROJECT DESCRIPTION............................................................................................................... 36 3 MATERIALS AND METHODS........................................................................................................ 37 3.1 MATERIALS..........................................................................................................................37 3.1.1 HARDWARE................................................................................................................ 37 3.1.2 REAGENTS................................................................................................................ 39 3.1.3 SOFTWARE................................................................................................................. 41 3.1.4 ANTIBODIES..............................................................................................................41 3.1.5 LAB MATERIALS......................................................................................................... 42 3.2 METHODS...........................................................................................................................43 3.2.1 CELL CULTURE 43 3.2.2 PREPARATION OF CELL SUSPENSIONS ............................................. .._.._.....43 3.2.3 FLOW CYTOMETRY....................................................................................................43 3.2.4 RADJOLABELJNG........................................................................................................ 46 3.2.5 SDS-PAG E.............................................................................................................47 3.2.6 RADIOACTIVE T L C ....................................................................................................48 3.2.7 GAMMA COUNTER STUDIES.....................................................................................50 3.2.8 ANIMAL HANDLING....................................................................................................52 3.2.9 IN VIVO IMAGING...................................................................................................... 53 3.2.10 EX WVO STUDIES...................................................................................................... 57 3.2.11 STATISTICAL ANALYSIS................................................................................................60 3.3 EXPERIMENTS.................................................................................................................... 61 3.3.1 GD2 EXPRESSION OF DIFFERENT CELL UNES ........................................................... 61 3.3.2 BINDING AND SPECIFICITY OF GD2 SPECIFIC ANTIBODIES....................... 61 3.3.3 OPTIMIZATION OF THE RADIOLABELING PROTOCOL .................................................... 62 3.3.4 CHARACTERIZATION OF RADIOLABELED ANTIBODIES.................................................63 3.3.5 IN VIVO EXPERIMENTS..............................................................................................66 3.3.6 EX VIVO STUDIES...................................................................................................... 68 3.3.7 CLINICAL TRANSLATION............................................................................................... 68 RESULTS...................................................................................................................................69 4.1 / * * * * 0 STUDIES............................................................................................................... 69 4.1.1 GD2 EXPRESSION OF DIFFERENT CELL U NES............................................................ 69 4.1.2 BINDING AND SPECIFICITY OF ANT!GD2 ANTIBODIES .............................................. 71 4.1.3 RADIOLABELING........................................................................................................ 72 4.1.4 THE INFLUENCE OF LABELING TO THE IMMUNOREACTJVITY ........................................ 74 4.1.5 CHARACTERIZATION OF RADIOLABELED ANTIBODIES..................................................76 4.2 /NWVO STUDIES............................................................................................................... 80 4.2.1 CHARACTERIZATION OF THE XENOGRAFT MODELS.......................................................80 4.2.2 TITRATION OF THE ANTIBODY DOSE FOR IMAGING ..................................................... 87 4.2.3 COMPARATIVE PET STUDY......................................................................................90 4.2.4 BLOCKING STUDIES....................................................................................................99 4.2.5 P RELOADINGPET..................................................................................................118 4.2.6 CLINICAL TRANSLATION............................................................................................. 121 DISCUSSION........................................................................................................................... 123 5.1 IMAGING AND THERAPY OF NEUROBLASTOMA...............................................................123 5.2 NUCLEAR MEDICINE........................................................................................................ 123 5.3 RADIOLABELING OF ANTIBODIES......................................................................................125 5.4 REDUCTION OF LMMUNOREACTVTY ................................................................................127 5.5 ANJMAL MODELS.............................................................................................................128 5.6 COMPARISON OF ANTIBODY BIODISTRIBUTION IN VIVO................................................... 129 5.7 COMPARISON OF DIFFERENT TUMOR M ODELS................................................................131 5.8 INJECTION. DOSE.............................................................................................................. 133 5.9 BLOCKING STUDIES........................................................................................... 134 5.10 ANTIBODY SINKS IN SPLEEN AND LIVER........................................................................136 5.11 OUTLOOK..........................................................................................................................139 5.12 CONCLUSION.................................................................................................................... 142 6 ABSTRACT.................................................................................................................................145 6.1 ENGLISH VERSION............................................................................................................145 6.2 G E * A N VERSION.......................................................................................................... 147 7 PUBLICATIONS..........................................................................................................................150 8 STATEM ENT............................................................................................................................. 151 9 BIBLIOGRAPHY..........................................................................................................................152
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spellingShingle	Schmitt, Julia In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma
subject_GND	(DE-588)4113937-9
title	In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma
title_auth	In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma
title_exact_search	In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma
title_full	In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma vorgelegt von Julia Schmitt
title_fullStr	In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma vorgelegt von Julia Schmitt
title_full_unstemmed	In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma vorgelegt von Julia Schmitt
title_short	In vitro and in vivo characterization of antibody based PET tracers for imaging of neuroblastoma
title_sort	in vitro and in vivo characterization of antibody based pet tracers for imaging of neuroblastoma
topic_facet	Hochschulschrift
url	http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029065125&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
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