Chapter 1 Introduction 1
1.1 General introduction 1
1.2 Aims and objectives of the thesis  6
Chapter 2 Literature review and theoretical part  7
2.1 Molecular imaging of cancer 7
2.1.1 Positron Emission Tomography  8
2.1.2 Optical imaging 19
2.2 Multimodal molecular imaging 21
2.2.1 Silicon nanoparticles as multimodal imaging agents 23
2.2.2 Factors affecting the biodistribution and pharmacokinetics of NPs 27
2.2.3 Tumor targeting strategies for molecular imaging agents 30
2.2.4 Targeted functionalization of NPs and BFCAs for imaging purposes 32
Chapter 3 Results and Discussion 35
3.1 Synthesis, characterization and radiolabeling studies of hexadentate bispidine-based bifunctional chelating agents 37
3.1.1 Synthesis of hexadentate bispidine-based ligands 39
3.1.2 Radiochemistry of modified bispidine derivatives 59
3.1.3 Conclusions 61
3.2 Design and synthesis of Bispidine-based TATE and sd antibody bioconjugates 63
3.2.1 Bispidine-based bioconjugates of somatostatin agonist TATE 63
3.2.2 Bispidine-based EGFR targeting sdAb conjugates B5-sdAb 71
3.2.3 Conclusions 80
3.3 Synthesis and characterization of amine-terminated ultrasmall Si NPs 81
3.3.1 Synthesis of amine-terminated Si NPs 81
3.3.2 Characterization of Si NPs 82
3.3.3 Surface characterization of Si NPs 84
3.3.4 Conclusions 85
3.4 Synthesis, characterization, and biodistribution studies of Si NP-based mono-labeled PET and optical imaging agents 86
3.4.1 Si NP-NOTA derived PET imaging agent 88
3.4.2 Synthesis and characterization of Si NP-Bispidine (Si NP-B4) 93
3.4.3 Synthesis, characterization, in vitro and in vivo evaluation of Si NP-IR800 as an optical imaging probe 95
3.4.5 Conclusions  104
3.5 Development of dual-labeled Si NPs an its in vitro and in vivo evaluation 106
3.5.1 Synthesis and characterization of Si NP-IR800-NOTA conjugate  107
3.5.2 Photophysical characterization of Si NP-IR800-NOTA and comparison with mono-labeled imaging agents 109
3.5.3 Radiolabeling studies of dual-labeled Si NP-IR800-NOTA 110
3.5.4 Quantitative estimation of the amount of fluorophore and the radiolabel on the Si NP conjugate 111
3.5.5 Cell Cytotoxicity Studies of the Si NP-IR800-NOTA  114
3.5.6 In vivo PET analysis and biodistribution studies, urine analysis and ex vivo examination of [64Cu]Cu-Si NP-IR800-NOTA  115 
3.5.7 Comparative analysis of [68Ga]Ga-Si NP-IR800-NOTA and [64Cu]Cu-Si NP-IR800-NOTA in A431 tumor bearing mice  121 
3.5.8 Conclusions  127
3.6 Investigation of mono-labeled and dual-labeled Si NPs as targeted imaging agents  128
3.6.1 Synthesis of Si NP-PEG-5B9 peptide conjugates  128
3.6.2 Characterization of the targeted Si NP conjugates 129
3.6.3 Conclusions  134
Chapter 4 Conclusions and Outlook  135
4.1 Conclusions 135
4.2 Outlook 140
Chapter 5 Experimental Section  141
5.1 Chemicals and Materials  141
5.2 Analysis, characterization and purification techniques and methods  143
5.3 Radionuclide production (68Ga and 64Cu) 146
5.4 Syntheses  148
5.4.1 Synthesis of bispidines derivatives (B1-B11), intermediates (B1’, B3’, B8’, B9’, B11’) and bifunctional linkers (L1, L2)  148
5.4.2 Synthesis of bispidines-based bioconjugates B4-PEG-TATE and B5-sdAb-7C12  160
5.4.3 Synthesis and modification of Si NPs by hydrothermal method  161
5.5 Radiolabeling experiments 166
5.6 In vitro cell experiments  167
5.7 Cell binding studies  169
5.8 Animal experiments 170
Chapter 6 References  172
Chapter 7 Annex  192
7.1 Acronyms 192
7.2 Supplementary Data  195
Chapter 8 Publications, Conferences and Awards  203
Chapter 9 Acknowledgements  206
Chapter 10 Statement of declaration / Erklärungen  208