The emerging role of copper-64 radiopharmaceuticals as cancer theranostics

Boschi, Alessandra; Martini, Petra; Janevik-Ivanovska, Emilija; Duatti, Adriano

doi:10.1016/j.drudis.2018.04.002

Cited by 86 publications

(73 citation statements)

References 95 publications

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“…Correspondingly, the ex vivo biodistribution data (Figure g) revealed a significant difference in uptake among the 64 Cu‐ l ‐G@SeNPs, 64 Cu‐ d ‐G@SeNPs, and 64 Cu‐ dl ‐G@SeNPs in the liver, spleen, pancreas, intestines, and kidney at 24 h p.i. In addition, for the nanosystem of either l ‐, d ‐, or dl ‐G@SeNPs, the chiral GSH, PC, and Se 2− (only in l ‐G@SeNPs) reduced some 64 Cu II to 64 Cu I , which disassociated from the nanoparticles in the form 64 Cu 2+ , which was quickly transported to the liver and eliminated through the bladder within 4 h, as demonstrated by the PET imaging.…”

Section: Resultsmentioning

confidence: 90%

Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles

Huang

et al. 2020

Angew Chem Int Ed

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The chirality of nanoparticles directly influences their transport and biological effects under physiological conditions, but the details of this phenomenon have rarely been explored. Herein, chiral GSH‐anchored selenium nanoparticles (G@SeNPs) are fabricated to investigate the effect of their chirality on their transport and antioxidant activity. G@SeNPs modified with different enantiomers show opposite handedness with a tunable circular dichroism signal. Noninvasive positron emission tomography imaging clearly reveals that 64Cu‐labeled l‐G@SeNPs experience distinctly different transport among the major organs from that of their d‐and dl‐counterparts, demonstrating that the chirality of the G@SeNPs influences the biodistribution and kinetics. Taking advantage of the strong homologous cell adhesion and uptake, l‐G@SeNPs have been shown here to effectively prevent oxidation damage caused by palmitic acid in insulinoma cells.

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Section: Resultsmentioning

confidence: 90%

Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles

Huang

et al. 2020

Angew Chem Int Ed

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“…Copper transporter 1 (CTR-1) is the major high-affinity copper transporter, which transports Cu(I) into the cells and deliver to the copper chaperone Cox17, the antioxidant protein 1 (Atox1), or the copper chaperone for superoxide dismutase (CCS). Atox1 further deliver copper to either the copper transporting adenosine triphosphatase (ATPase) ATP7A in neuron/astrocyte cells, or the ATPase ATP7B in the liver, which either pass the copper to target cuproenzymes, or to excretion [95][96][97][98][99]. Peng et al reported a significantly higher [ 64 Cu]CuCl 2 uptake in tumor tissue compared to normal tissue, meanwhile observing a substantial increase of CTR-1 expression in tumor but not in normal tissue [25].…”

Section: Copper Metabolismmentioning

confidence: 99%

Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: a review of current evidence and discussion of the retention mechanisms

et al. 2020

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Background: Tumor hypoxia (low tissue oxygenation) is an adverse condition of the solid tumor environment, associated with malignant progression, radiotherapy resistance, and poor prognosis. One method to detect tumor hypoxia is by positron emission tomography (PET) with the tracer [ 64 Cu][Cu-diacetyl-bis(N(4)methylthiosemicarbazone)] ([ 64 Cu][Cu(ATSM)]), as demonstrated in both preclinical and clinical studies. In addition, emerging studies suggest using [ 64 Cu][Cu(ATSM)] for molecular radiotherapy, mainly due to the release of therapeutic Auger electrons from copper-64, making [ 64 Cu][Cu(ATSM)] a "theranostic" agent. However, the radiocopper retention based on a metal-ligand dissociation mechanism under hypoxia has long been controversial. Recent studies using ionic Cu(II) salts as tracers have raised further questions on the original mechanism and proposed a potential role of copper itself in the tracer uptake. We have reviewed the evidence of using the copper radiopharmaceuticals [ 60/61/62/64 Cu][Cu(ATSM)]/ionic copper salts for PET imaging of tumor hypoxia, their possible therapeutic applications, issues related to the metal-ligand dissociation mechanism, and possible explanations of copper trapping based on studies of the copper metabolism under hypoxia. Results:We found that hypoxia selectivity of [ 64 Cu][Cu(ATSM)] has been clearly demonstrated in both preclinical and clinical studies. Preclinical therapeutic studies in mice have also demonstrated promising results, recently reporting significant tumor volume reductions and improved survival in a dose-dependent manner. Cu(II)-[Cu(ATSM)] appears to be accumulated in regions with substantially higher CD133 + expression, a marker for cancer stem cells. This, combined with the reported requirement of copper for activation of the hypoxia inducible factor 1 (HIF-1), provides a possible explanation for the therapeutic effects of [ 64 Cu][Cu(ATSM)]. Comparisons between [ 64 Cu][Cu(ATSM)] and ionic Cu(II) salts have showed similar results in both imaging and therapeutic studies, supporting the argument for the central role of copper itself in the retention mechanism.Conclusions: We found promising evidence of using copper-64 radiopharmaceuticals for both PET imaging and treatment of hypoxic tumors. The Cu(II)-[Cu(ATSM)] retention mechanism remains controversial and future mechanistic studies should be focused on understanding the role of copper itself in the hypoxic tumor metabolism.

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“…In this case, the radioactivity coming from the radiopharmaceutical, carrying the diagnostic information outward from the body, is detected and transformed in a very precise picture of the radiopharmaceutical's distribution in the body by means of so-called "gamma cameras" working with sophisticated computerized algorithms. On the contrary, radionuclides decaying through the emission of massive particles, such as electrons or alphas, can be used in nuclear medicine for radionuclide therapy to treat certain types of cancer and other diseases [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

A Picture of Modern Tc-99m Radiopharmaceuticals: Production, Chemistry, and Applications in Molecular Imaging

2019

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Even today, techentium-99m represents the radionuclide of choice for diagnostic radio-imaging applications. Its peculiar physical and chemical properties make it particularly suitable for medical imaging. By the use of molecular probes and perfusion radiotracers, it provides rapid and non-invasive evaluation of the function, physiology, and/or pathology of organs. The versatile chemistry of technetium-99m, due to its multi-oxidation states, and, consequently, the ability to produce a variety of complexes with particular desired characteristics, are the major advantages of this medical radionuclide. The advances in technetium coordination chemistry over the last 20 years, in combination with recent advances in detector technologies and reconstruction algorithms, make SPECT’s spatial resolution comparable to that of PET, allowing 99mTc radiopharmaceuticals to have an important role in nuclear medicine and to be particularly suitable for molecular imaging. In this review the most efficient chemical methods, based on the modern concept of the 99mTc-metal fragment approach, applied to the development of technetium-99m radiopharmaceuticals for molecular imaging, are described. A specific paragraph is dedicated to the development of new 99mTc-based radiopharmaceuticals for prostate cancer.

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The emerging role of copper-64 radiopharmaceuticals as cancer theranostics

Cited by 86 publications

References 95 publications

Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles

Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles

Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: a review of current evidence and discussion of the retention mechanisms

A Picture of Modern Tc-99m Radiopharmaceuticals: Production, Chemistry, and Applications in Molecular Imaging

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