Theranostics, Gallium-68, and Other Radionuclides

Transcription

1 Recent Results in Cancer Research 194 Theranostics, Gallium-68, and Other Radionuclides A Pathway to Personalized Diagnosis and Treatment Bearbeitet von Richard P. Baum, Frank Rösch 1. Auflage Buch. XVIII, 576 S. Hardcover ISBN Format (B x L): 15,5 x 23,5 cm Gewicht: 1052 g Weitere Fachgebiete > Medizin > Klinische und Innere Medizin > Onkologie, Psychoonkologie Zu Leseprobe schnell und portofrei erhältlich bei Die Online-Fachbuchhandlung beck-shop.de ist spezialisiert auf Fachbücher, insbesondere Recht, Steuern und Wirtschaft. Im Sortiment finden Sie alle Medien (Bücher, Zeitschriften, CDs, ebooks, etc.) aller Verlage. Ergänzt wird das Programm durch Services wie Neuerscheinungsdienst oder Zusammenstellungen von Büchern zu Sonderpreisen. Der Shop führt mehr als 8 Millionen Produkte.

2 Contents Part I Generators 68 Ge/ 68 Ga Generators: Past, Present, and Future Introduction The Early Years ( ): The Dawn of 68 Ga Further Generator Developments: Al 2 O 3 -Based EDTA-Eluted Generators Ga-EDTA: The PET Pharmaceutical, Development of Positron Scintillation Cameras Hibernating 68 Ga Medical Applications, but New Chemistry Ahead Commercial Ionic Generators Current State/Outlook References Overview and Perspectives on Automation Strategies in 68 Ga Radiopharmaceutical Preparations Introduction Approach to Automation: Considerations on 68 Ga Radiolabeling Process Modules for 68 Ga Radiopharmaceuticals Classification and Characteristics of Automated Systems Automation and Regulatory Aspects Perspectives References Post-Processing via Cation Exchange Cartridges: Versatile Options Introduction The Initial Cation Exchange-Based Post-Purification Concept v

3 vi Contents 3 Combined Cation and Anion Exchange-Based Post-Processing Post-Processing Towards Nonaqueous Systems for Labeling Lipophilic Compounds Instant Quantification of Generator 68 Ge Breakthrough Conclusions References Ga Generator Integrated System: Elution Purification Concentration Integration Introduction Nuclear Characteristics and Radioactive Transformation Equilibrium Ge/ 68 Ga Separation and 68 Ga Generator Nanocrystalline Ceramic Structure Sorbent Used for Chromatographic 68 Ge/ 68 Ga Separation Ga Generator Setup Generator Operation and Specification Zn 2+ Formation and Its Influence on Coordination Chemistry of 68 Ga-Radiolabeling Post-Elution Purification Concentration of 68 Ga Eluate Salt-Form Cationic Exchange Resin-Based Purification Concentration Method Automation Process and Setup of 68 Ga Radioisotope Generator Integrated System (RADIGIS- 68 Ga) Basic/Acidic 68 Ga Eluates and Their Radiolabeling Performance of 68 Ga Generator and 68 Ga Radioisotope Generator Integrated System Quality Evaluation Experiments: Quality Control Protocols and Radiolabeling Efficacy Evaluation Quality Evaluation of 68 Ga Solution Operation Performance Assessment of Ga-68 Generator Systems References Purification and Labeling Strategies for 68 Ga from 68 Ge/ 68 Ga Generator Eluate Introduction History Current State Basic Methods Combined Cationic Anionic Purification of 68 Ge/ 68 Ga Generator Eluate for Labeling of Fragile Peptides and Proteins Aim Description

4 Contents vii 2.3 Advantages Example: Synthesis of 68 Ga-BPAMD A New Highly Efficient NaCl-Based Cationic 68 Ge/ 68 Ga Generator Eluate Purification: The Basis for Effective 68 Ga Labeling Aim Labeling Strategy Description of the Method Results References Ga and 68 Ga Purification Studies: Preliminary Results Introduction Materials and Methods Ge/ 68 Ga Generator and 67 Ga Materials Water Purification Ga Purification on Cation Exchange Resin Ga/ 68 Ga Purification: Isopropyl Ether Extraction System Results and Discussion Ge/ 68 Ga Generator Performance Water Purification Ga/ 68 Ga Purification on Cation Exchange Resin Ga/ 68 Ga Purification Using Isopropyl Ether Extraction System Conclusion References Part II Radiochemistry and Radiopharmacy The Diversity of 68 Ga-Based Imaging Agents Introduction Targeted Imaging Imaging Somatostatin Receptors Imaging Human Epidermal Growth Factor Receptor (HER) Family Imaging Angiogenesis Antisense Oligonucleotide-Based Tracers Pretargeted Imaging Nontargeted Imaging Low-Molecular-Weight Imaging Agents Further Examples of Diverse Applications of 68 Ga Conclusions References

5 viii Contents Nanoparticles and Phage Display Selected Peptides for Imaging and Therapy of Cancer Introduction Biomarkers Nanoparticles Gold Radioisotope Properties Gum Arabic Gold Nanoparticles Epigallocatechin-Gallate Gold Nanoparticles Bombesin Gold Nanoparticles DTDTPA Gold Nanoparticles for Molecular Imaging Alpha-Emitting Sequestering Nanoparticles Phage Display References Click -Cyclized 68 Ga-Labeled Peptides for Molecular Imaging and Therapy: Synthesis and Preliminary In Vitro and In Vivo Evaluation in a Melanoma Model System Introduction Targeted Peptides for Molecular Imaging and Therapy Cyclized Melanocyte Stimulating Hormone Experimental Chemicals and Reagents Peptide Synthesis In Vitro Competitive Binding Assay Radiochemistry Serum Stability Assay In Vivo PET Imaging and Biodistribution Studies Results Peptide Synthesis Radiolabeling In Vitro Competitive Binding Assays Serum Stability In Vivo Biodistribution and Imaging Discussion Click Cyclizations and Peptide Synthesis In Vitro Evaluation In Vivo Biodistributions and PET Imaging Summary and Conclusions References Early Experience with 68 Ga-DOTATATE Preparation Introduction Materials and Methods DOTA-Tyr 3 -Octreotate

6 Contents ix Ge/ 68 Ga Generator Ga Radiolabeling Scan Procedure Results and Discussion Generator Elution Profile Post-Elution Processing Radiolabeling Loss of Radioactivity During Radiolabeling Clinical Imaging Patient Complaints Regulatory Requirement for Routine Clinical Use Number of Cases Future Directions Lessons Learnt Conclusion References Ga-Radiopharmaceuticals for PET Imaging of Infection and Inflammation Introduction Overview on Infection Imaging Labeled Leukocytes for Imaging Infection Labeled Antibiotics for Infection Imaging Ga-Citrate for Infection Imaging Difference Between 67 Ga-SPECT and 68 Ga-PET Production of 67 Ga and Pure 68 Ga Development of 68 Ga Chemistry Mechanism of Cellular Uptake of Ga-Citrate Application of 68 Ga-Radiopharmaceuticals for Infection Imaging Biodistribution of 67 Ga/ 68 Ga-Citrate in Normal Rats and Humans Ga-Citrate PET for Imaging Staph A Infection in an Animal Model Ga-Citrate for Diagnostic PET Imaging of Osteomyelitis and Follow-Up Treatment Ga-Citrate PET/CT for Imaging of Discitis, Cellulitis, 4.5 and Abscess Ga-Apo-Transferrin ( 68 Ga-TF) for PET Imaging of Bacterial Infection Comparison of 68 Ga-Chloride and 18 F-FDG for PET Imaging of Osteomyelitis and Human Pancreatic Adenocarcinoma Xenografts in Rats Evaluation of 99m Tc- and 68 Ga-Glucosamine for Imaging Inflammatory Arthritis

7 x Contents 5.1 Chemical Structures of Glucose Analogs and Synthesis of 99m Tc-Labeled Deoxyglucosamine Synthesis of 68 Ga-Glucosamine and Preliminary Results Conclusion References Ga-Labeled Bombesin Analogs for Receptor-Mediated Imaging Introduction Bombesin Receptors and Their Ligands Targeted Approach to Receptor-Mediated Imaging Why Bombesin Receptor-Mediated Imaging? Gallium Radiometal Chelating Systems Special Focus on Gallium-Labeled Bombesin Analogs Conclusion References A Novel 68 Ga-Labeled Pteroic Acid-Based PET Tracer for Tumor Imaging via the Folate Receptor Introduction Results and Discussion Synthesis Radiolabeling and In Vitro Studies Conclusion Experimental Benzyl-N-(2-hydroxyethyl)carbamate N-Benzyloxycarbonyl-2-bromoethylamine (N-Benzyloxycarbonyl-ethylamine)-1,4,7,10- tetraazacyclododecane (N-Benzyloxycarbonyl-ethylamine)-4,7,10- tris(tert-butyl-acetate)-1,4,7,10-tetraaza-cyclododecane (Aminoethyl)-4,7,10-tris(tert-butyl-acetate)- 1,4,7,10-tetraazacyclododecane tert-butyl 2,2 0,2 00 -(10-(2-(4-(N-((2-((dimethylamino) methyleneamino)-4-oxo-3,4-dihydropteridin-6-yl) methyl)formamido)benzamido)ethyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyl)triacetate ,2 0,2 00 (10-(2-(4-((2-Amino-4-oxo-3,4-dihydropteridin-6-yl) methylamino)benzamido)ethyl)-1,4,7,10-tetraazacyclododecane- 1,4,7-triyl)triacetic acid Radiolabeling Stability Studies Lipophilicity Assay References

8 Contents xi Measurement of Protein Synthesis: In Vitro Comparison of 68 Ga-DOTA-Puromycin, [ 3 H]Tyrosine, and 2-Fluoro-[ 3 H]tyrosine Introduction Methods Equipment and Reagents Ga Production Synthesis of DOTA-NHC 6 -dc-puromycin (DOTA-Pur) Ga-Labeling of DOTA-Pur In Vitro Studies In Vitro Uptake and Protein Incorporation Inhibition of 68 Ga-DOTA-Pur, [ 3 H]Tyrosine, and 2-Fluoro-[ 3 H]tyrosine Incorporation into Proteins Statistical Analysis Results Synthesis of DOTA-NHC 6 -dc-puromycin Ga-Labeling of DOTA-Pur In Vitro Uptake and Protein Incorporation Inhibition of Protein Synthesis lpet Imaging in Tumor-Bearing Rats Discussion Conclusions References Hypoxia Imaging Agents Labeled with Positron Emitters Introduction Hypoxia Why Is Detection of Tumor Hypoxia Important? Nature of an Ideal Hypoxia Imaging Agent for Hypoxia Imaging Nitroimidazole as Hypoxic Agent Copper(II)-Diacetyl-bis(N 4 -methylthiosemicarbazone) (Cu-ATSM) as Hypoxic Agent Retention of Radiolabeled Compounds in EMT6 Cells Conclusions References Lu/ 90 Y Intermediate-Affinity Monoclonal Antibodies Targeting EGFR and HER2/c-neu: Preparation and Preclinical Evaluation Introduction Materials and Methods Conjugation of Monoclonal Antibodies Flow Cytometric Analysis Radiolabeling Quality Control

9 xii Contents 2.5 Cell Culture Binding Saturation and Competitive Assays Cytotoxicity Study In Vivo Studies Influence of Increasing Amount of BFC per mab Influence of the Nature of the Chelate on the In Vivo Behavior of the Radioimmunoconjugate Biodistribution of 177 Lu-Nimotuzumab in Mice Bearing SNU-C2B Xenograft Biodistribution of 177 Lu-Nimotuzumab in Mice Bearing A431 Xenograft Statistical Analysis Results and Discussion Antibody Modification and Radiochemistry In Vitro Studies In Vivo Studies Conclusion References Part III Molecular Imaging Using 68 Ga Labeled Tracers Divergent Role of 68 Ga-Labeled Somatostatin Analogs in the Workup of Patients with NETs: AIIMS Experience Introduction Epidemiology Our Study Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) Classification Functional Imaging of GEP-NETs Studies with SRS (Somatostatin Receptor Scintigraphy) Studies with 68 Ga-Labeled Octreotide Analogs Ga-DOTATOC/NOC Synthesis Ga-DOTA-Peptide Imaging Protocol Normal Biodistribution of 68 Ga-Labeled Somatostatin Peptides Sporadic GEP-NETs Metastatic GEP-NETs with Occult/Uncertain Primary Tumor Gastroenteropancreatic Neuroendocrine Tumors in Patients with Hereditary Syndromes Correlation of Tumor Uptake with Cellular Differentiation Correlation of Tumor Uptake with SSTR Subtypes Impact on Management Role of FDG-PET/CT Pulmonary Neuroendocrine Tumors

10 Contents xiii 20 Medullary Carcinoma Thyroid Pheochromocytoma and Paraganglioma Ectopic ACTH-Producing Tumors Conclusions References Differential Uptake of 68 Ga-DOTATOC and 68 Ga-DOTATATE in PET/CT of Gastroenteropancreatic Neuroendocrine Tumors Introduction Patients and Methods Patients Radiopharmaceutical Preparation Ga-DOTATOC and 68 Ga-DOTATATE Imaging Image Evaluation Statistical Analysis Results Regional and Lesional Analyses SUV Analyses Discussion Lesion Detection Tumor Uptake Renal Uptake Conclusion References High Uptake of 68 Ga-DOTATOC in Spleen as Compared to Splenosis: Measurement by PET/CT Introduction Materials and Methods Results Initial Staging SSTR PET/CT Postpancreatectomy SSTR PET/CT Pre PRRNT Restaging SSTR PET/CT Post PRRNT Discussion Conclusions References Rare Metastases Detected by 68 Ga-Somatostatin Receptor PET/CT in Patients with Neuroendocrine Tumors Introduction Prevalence and Location of Rare Metastases of Neuroendocrine Tumors Cardiac Metastases Breast Metastases

11 xiv Contents 2.3 Retro-Orbital Soft Tissue Uterus, Testes, and Seminal Vesicles Brain Spleen Discussion References Comparison of Different Positron Emission Tomography Tracers in Patients with Recurrent Medullary Thyroid Carcinoma: Our Experience and a Review of the Literature Introduction Our Experience Patients PET/CT Protocol and Data Analysis Statistical Analysis Results Literature Review Discussion Conclusion References PET Lung Ventilation/Perfusion Imaging Using 68 Ga Aerosol (Galligas) and 68 Ga-Labeled Macroaggregated Albumin Introduction Background Objective Materials and Methods Materials Methods Exploratory Studies Results Ga-Labeled Human Serum Albumin Microspheres Exploratory Studies Dosimetry Discussion Ga-Labeled Radiotracer for Lung Ventilation and Perfusion Imaging Dosimetry Perspectives References

12 Contents xv Combined PET/MR Imaging Using 68 Ga-DOTATOC for Radiotherapy Treatment Planning in Meningioma Patients Introduction Methods PET/MR Tomography Diagnosis and RT Treatment Planning of Meningioma Ga-DOTATOC PET/MR Protocol Radiotherapy Treatment Planning Clinical Examples Discussion Conclusion References Part IV Targeted Radiotherapy (Peptide Receptor Radionuclide Therapy) and Dosimetry A Rare Case of a Large Spinal Meningioma with Mediastinal Extension and Malignant Behavior Classified Histologically as Benign Case Presentation Clinical Findings Histology and Genetic Analyses Pretherapeutic Imaging Therapy Discussion References Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors in Germany: First Results of a Multi-institutional Cancer Registry Introduction Patients and Methods Results Discussion References Polish Experience in Peptide Receptor Radionuclide Therapy Introduction Materials and Methods Radiopharmaceuticals Treatment Procedure Evaluation of Results and Assessment of Clinical Benefit Results

13 xvi Contents 3.1 Side-Effects of Treatment Discussion Conclusions References PRRT as Neoadjuvant Treatment in NET Introduction Methods and Results Conclusion References Intraoperative Somatostatin Receptor Detection After Peptide Receptor Radionuclide Therapy with 177 Lu- and 90 Y-DOTATOC (Tandem PRRNT) in a Patient with a Metastatic Neuroendocrine Tumor Introduction Materials and Methods Results Discussion and Conclusions References Personalized Image-Based Radiation Dosimetry for Routine Clinical Use in Peptide Receptor Radionuclide Therapy: Pretherapy Experience Introduction Challenges in Patient-Specific Dosimetry for Radionuclide Therapy General Concepts in Internal Dosimetry Key Elements of Internal Dose Calculations Imaging Protocol Image Reconstruction Segmentation of Nuclear Medicine Images Dose Calculation Method Software Tools for Dosimetry Calculations Clinical Implementation of the Proposed Dose Calculation Technique Patient Image Acquisition Phantom Experiments to Calibrate Parameters for the Adaptive Threshold Technique Data Processing Dosimetry Results Therapy Conclusions References

14 Contents xvii The Bad Berka Dose Protocol: Comparative Results of Dosimetry in Peptide Receptor Radionuclide Therapy Using 177 Lu-DOTATATE, 177 Lu-DOTANOC, and 177 Lu-DOTATOC Introduction Patients and Methods Patients Radiopharmaceuticals Infusion and Renal Protection Dosimetry Comparison and Statistics Results Normal Organs Tumor Lesions Tumor-to-Kidney Ratio Variability Discussion Conclusions References D SPECT/CT Acquisition for 3D Dose Calculation and Dose Planning in 177 Lu-Peptide Receptor Radionuclide Therapy: Applications for Clinical Routine Introduction and Background Information Methods and Materials Dose Calculation Clinical Practice Results Discussion Conclusions and Summary of the Results References Peptide Receptor Radionuclide Therapy with 177 Lu Labeled Somatostatin Analogs DOTATATE and DOTATOC: Contrasting Renal Dosimetry in the Same Patient Introduction Patients and Methods Patients Radiopharmaceuticals Infusion and Renal Protection Monitoring of Renal Function Dosimetry Comparison and Statistics Results Discussion

15 xviii Contents 5 Conclusions References Is There a Correlation Between Peptide Receptor Radionuclide Therapy-Associated Hematological Toxicity and Spleen Dose? Background Patients and Methods Patients Dosimetry Statistics Results Conclusion References Old and New Peptide Receptor Targets in Cancer: Future Directions Introduction Somatostatin Receptors Bombesin Receptors Incretin Receptors Conclusion References