Development of an automated production process of [64 Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications

J Labelled Comp Radiopharm. 2022 Jun 15;65(7):191-202. doi: 10.1002/jlcr.3973. Epub 2022 Apr 29.

Abstract

Cyclotron-produced copper-64 radioisotope tracers offer the possibility to perform both diagnostic investigation by positron emission tomography (PET) and radiotherapy by a theranostic approach with bifunctional chelators. The versatile chemical properties of copper add to the importance of this isotope in medicinal investigation. [64 Cu][Cu (ATSM)] has shown to be a viable candidate for imaging of tumor hypoxia; a critical tumor microenvironment characteristic that typically signifies tumor progression and resistance to chemo-radiotherapy. Various production and radiosynthesis methods of [64 Cu][Cu (ATSM)] exist in labs, but usually involved non-standardized equipment with varying production qualities and may not be easily implemented in wider hospital settings. [64 Cu][Cu (ATSM)] was synthesized on a modified GE TRACERlab FXN automated synthesis module. End-of-synthesis (EOS) molar activity of [64 Cu][Cu (ATSM)] was 2.2-5.5 Ci/μmol (HPLC), 2.2-2.6 Ci/μmol (ATSM-titration), and 3.0-4.4 Ci/μmol (ICP-MS). Radiochemical purity was determined to be >99% based on radio-HPLC. The final product maintained radiochemical purity after 20 h. We demonstrated a simple and feasible process development and quality control protocols for automated cyclotron production and synthesis of [64 Cu][Cu (ATSM)] based on commercially distributed standardized synthesis modules suitable for PET imaging and theranostic studies.

Keywords: 64Cu-ATSM; PET; Tracerlab; automated synthesis; hypoxia; radiolabeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia
  • Coordination Complexes / chemistry*
  • Copper Radioisotopes
  • Organometallic Compounds* / chemistry
  • Positron-Emission Tomography / methods
  • Precision Medicine
  • Radiopharmaceuticals
  • Thiosemicarbazones / chemistry*

Substances

  • Coordination Complexes
  • Copper Radioisotopes
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Thiosemicarbazones
  • copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)