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The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2020 Oct 07

DOI: 10.23736/S1824-4785.20.03285-9

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

Copper-64 based radiopharmaceuticals for brain tumors and hypoxia imaging

Micol PASQUALI 1, Petra MARTINI 1, 2, Arman SHAHI 3, Amir R. JALILIAN 4, Joao OSSO Jr. 4, Alessandra BOSCHI 5

1 National Institute of Nuclear Physics, National Laboratories of Legnaro, Legnaro, Padua, Italy; 2 Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy; 3 Faculty of Science, McMaster University, Hamilton, ON, Canada; 4 Department of Nuclear Science and Applications, International Atomic Energy Agency (IAEA), Vienna, Austria; 5 Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy


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INTRODUCTION: The most common and aggressive primary malignancy of the central nervous system is Glioblastoma that, as a wide range of malignant solid tumor, is characterized by extensive hypoxic regions. A great number of PET radiopharmaceuticals have been developed for the identification of hypoxia in solid tumors, among these, we find copper-based tracers. The object of the current review paper is to provide an overview of radiocopper compounds applied for preclinical and clinical research in brain tumors and hypoxia imaging or therapy.
EVIDENCE ACQUISITION: Copper offers a wide variety of isotopes, useful for nuclear medicine applications, but only 64Cu and 67Cu are under the spotlight of the scientific community since being good candidates for theranostic applications. Between the two, 64Cu availability and production cost have attracted more interest of the scientific community.
EVIDENCE SYNTHESIS: In order to better understand the application of copper-bis thiosemicarbazones in hypoxia imaging, an overview of the role of hypoxia in cancer, existing non-imaging and imaging techniques for hypoxia identification and promising future avenues regarding hypoxia is necessary. Different proposed uptake mechanisms of [64Cu][Cu(ATSM)] inside the cell will be discussed and other 64Cu-based tracers for brain tumors described.
CONCLUSIONS: Among radio copper compounds [64Cu][Cu(ATSM)] is the most studied radiopharmaceutical for imaging and treatment of brain tumors. Experimental evidence suggested that [64Cu][Cu(ATSM)] could be more appropriately considered as a marker of over-reduced intracellular state rather than a pure hypoxia agent. Moreover, preliminary clinical data suggested that [64Cu]CuCl2 can be a potentially useful diagnostic agent for malignancies of the central nervous system (CNS).


KEY WORDS: Copper-64; Brain tumors; Neuroimaging; Glioblastoma; PET radiopharmaceuticals

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