Positron emission tomography (PET) is an important clinical tool, and with its longer half-life, copper-64 has several unique attributes that make it a multi-purpose radionuclide with many potential applications. Additionally, copper as a trace element plays a pivotal role in several human metabolic and pathologic diseases and is involved in malignant cells biochemistry pathways. This offers the opportunity for scientists to explore the theranostic capabilities of copper-64. This current publication, arising from an IAEA Coordinated Research Project, describes the biochemical and radiopharmaceutical aspects of copper-64, and its clinical applications, with specific guidelines and methods for the production of copper-64 chloride, peptide and monoclonal antibody radiopharmaceuticals. It is expected to be of use to all professionals involved in the field by specifying ideal production, formulation and quality control methods.

• 1. INTRODUCTION
  • 1.1. Background
  • 1.2. Objective
  • 1.3. Scope
  • 1.4. Structure
• 2. COPPER-64 PRODUCTION
  • 2.1. Decay scheme
  • 2.2. Routes of production
    • 2.2.1. Reactor production
    • 2.2.2. Cyclotron
    • 2.2.3. Target solution
    • 2.2.4. Target irradiation
    • 2.2.5. Separation of produced copper-64
    • 2.2.6. Quality control
    • 2.2.7. Target material recovery
• 3. CHELATING LIGANDS FOR COPPER
  • 3.1. Acyclic chelators
  • 3.2. Macrocyclic chelators
    • 3.2.1. Ring size effect
    • 3.2.2. Polyaza carboxylate, phosphonate and sarcophagine chelators
    • 3.2.3. Porphyrins
• 4. COPPER-64 RADIOLABELLED PEPTIDES
  • 4.1. Introduction
  • 4.2. Radiochemistry of copper-64
  • 4.3. Peptides
    • 4.3.1. Somatostatin receptor targeting peptides
    • 4.3.2. Gastrin releasing peptide receptor targeting peptides
    • 4.3.3. Melanocortin receptor targeting peptides
    • 4.3.4. Integrin receptor targeting peptides
    • 4.3.5. Multivalent receptor targeting peptides
    • 4.3.6. Prostate specific membrane antigen
• 5. COPPER-64 LABELLED ANTIBODIES
  • 5.1. Introduction
  • 5.2. Antibody conjugations and quality control
  • 5.3. Antibody radiolabelling and quality control
• 6. COPPER-64 DICHLORIDE RADIOPHARMACEUTICAL
  • 6.1. Introduction
  • 6.2. Formulation and quality control
  • 6.3. Biodistribution
  • 6.4. Dosimetry
    • 6.4.1. Organ dosimetry
    • 6.4.2. Cellular microdosimetry
    • 6.4.3. Nanodosimetry
  • 6.5. [64Cu]CuCl2 for PET molecular imaging
  • 6.6. [64Cu]CuCl2 as a theranostic agent
  • 6.7. True theranostic pairs of copper
• 7. CLINICAL APPLICATIONS OF COPPER-64 RADIOPHARMACEUTICALS
  • 7.1. Introduction
  • 7.2. [64Cu]CuCl2 in oncological applications
  • 7.3. 64Cu-PSMA ligands
  • 7.4. 64Cu somatostatin receptors
  • 7.5. [64Cu]CuCl2 applications in metabolic diseases
• CONCLUSIONS
• REFERENCES
• Annex I COPPER IN LIFE
• Annex II COPPER BIOLOGY
• Annex III DETAILED PROCEDURE FOR THE DEVELOPMENT OF A 64Cu-NOTA-mAb FOR PET APPLICATIONS
• ABBREVIATIONS
• CONTRIBUTORS TO DRAFTING AND REVIEW