Copper, gallium and zirconium positron emission tomography imaging agents: The importance of metal ion speciation

McInnes, Lachlan E.; Rudd, Stacey E.; Donnelly, Paul S.

doi:10.1016/j.ccr.2017.05.011

Cited by 55 publications

(36 citation statements)

References 136 publications

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“…However, the simple use of DFOB as a chelating drug for Al(III) will seriously interfere with iron metabolism. As for gallium, its complexes with DFOB have been studied for application in diagnostic imaging with the positron emission tomography (PET) technique, using the isotope 68 Ga [ 26 ]. In the series of the 13th group, the stability of the complexes with Al(III), Ga(III) and In(III) decreases as the ionic radius increases, as expected.…”

Section: Solution Equilibria Studiesmentioning

confidence: 99%

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Bellotti

Remelli

2021

Molecules

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Deferoxamine B is an outstanding molecule which has been widely studied in the past decade for its ability to bind iron and many other metal ions. The versatility of this metal chelator makes it suitable for a number of medicinal and analytical applications, from the well-known iron chelation therapy to the most recent use in sensor devices. The three bidentate hydroxamic functional groups of deferoxamine B are the centerpiece of its metal binding ability, which allows the formation of stable complexes with many transition, lanthanoid and actinoid metal ions. In addition to the ferric ion, in fact, more than 20 different metal complexes of deferoxamine b have been characterized in terms of their chemical speciation in solution. In addition, the availability of a terminal amino group, most often not involved in complexation, opens the way to deferoxamine B modification and functionalization. This review aims to collect and summarize the available data concerning the complex-formation equilibria in solutions of deferoxamine B with different metal ions. A general overview of the progress of its applications over the past decade is also discussed, including the treatment of iron overload-associated diseases, its clinical use against cancer and neurodegenerative disorders and its role as a diagnostic tool.

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Section: Solution Equilibria Studiesmentioning

confidence: 99%

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Bellotti

Remelli

2021

Molecules

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“…This is of particular interest for radiolabeling of biomolecules undergoing slow distribution in vivo . Investigations on the coordination chemistry of 89 Zr 4+ in aqueous media indicate the preference of an octadentate ligand for stable complexation of the radionuclide 1,2. Despite intensive work on the design of novel octadentate chelators for zirconium-89,3–9 the linear siderophore-based hexadentate ligand desferrioxamine B (DFO) still is the most widely used chelator for 89 Zr-radiopharmaceuticals under clinical investigation, in particular monoclonal antibodies 10…”

Section: Introductionmentioning

confidence: 99%

Cyclic versus Noncyclic Chelating Scaffold for ⁸⁹Zr-Labeled ZEGFR:2377 Affibody Bioconjugates Targeting Epidermal Growth Factor Receptor Overexpression

et al. 2017

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Zirconium-89 is an emerging radionuclide for positron emission tomography (PET) especially for biomolecules with slow pharmacokinetics as due to its longer half-life, in comparison to fluorine-18 and gallium-68, imaging at late time points is feasible. Desferrioxamine B (DFO), a linear bifunctional chelator (BFC) is mostly used for this radionuclide so far but shows limitations regarding stability. Our group recently reported on fusarinine C (FSC) with similar zirconium-89 complexing properties but potentially higher stability related to its cyclic structure. This study was designed to compare FSC and DFO head-to-head as bifunctional chelators for 89Zr-radiolabeled EGFR-targeting ZEGFR:2377 affibody bioconjugates. FSC-ZEGFR:2377 and DFO-ZEGFR:2377 were evaluated regarding radiolabeling, in vitro stability, specificity, cell uptake, receptor affinity, biodistribution, and microPET-CT imaging. Both conjugates were efficiently labeled with zirconium-89 at room temperature but radiochemical yields increased substantially at elevated temperature, 85 °C. Both 89Zr-FSC-ZEGFR:2377 and 89Zr-DFO-ZEGFR:2377 revealed remarkable specificity, affinity and slow cell-line dependent internalization. Radiolabeling at 85 °C showed comparable results in A431 tumor xenografted mice with minor differences regarding blood clearance, tumor and liver uptake. In comparison 89Zr-DFO-ZEGFR:2377, radiolabeled at room temperature, showed a significant difference regarding tumor-to-organ ratios. MicroPET-CT imaging studies of 89Zr-FSC-ZEGFR:2377 as well as 89Zr-DFO-ZEGFR:2377 confirmed these findings. In summary we were able to show that FSC is a suitable alternative to DFO for radiolabeling of biomolecules with zirconium-89. Furthermore, our findings indicate that 89Zr-radiolabeling of DFO conjugates at higher temperature reduces off-chelate binding leading to significantly improved tumor-to-organ ratios and therefore enhancing image contrast.

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“…Since Ga(III) is a biomimetic of Fe(III), injection of 68 Ga-citrate selectively leads to the formation of 68 Ga-transferrin in vivo, which enables the imaging of tumors expressing the transferrin receptor [206]. However, 68 Ga-transferrin also exhibits a high blood pool activity and accumulation in the lungs, thus resulting in high background activity [207].…”

Section: Metal Complexes In Liver Specific Pet Diagnosticsmentioning

confidence: 99%

Metal-Based Complexes as Pharmaceuticals for Molecular Imaging of the Liver

2019

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This article reviews the use of metal complexes as contrast agents (CA) and radiopharmaceuticals for the anatomical and functional imaging of the liver. The main focus was on two established imaging modalities: magnetic resonance imaging (MRI) and nuclear medicine, the latter including scintigraphy and positron emission tomography (PET). The review provides an overview on approved pharmaceuticals like Gd-based CA and 99mTc-based radiometal complexes, and also on novel agents such as 68Ga-based PET tracers. Metal complexes are presented by their imaging modality, with subsections focusing on their structure and mode of action. Uptake mechanisms, metabolism, and specificity are presented, in context with advantages and limitations of the diagnostic application and taking into account the respective imaging technique.

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Copper, gallium and zirconium positron emission tomography imaging agents: The importance of metal ion speciation

Cited by 55 publications

References 136 publications

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Cyclic versus Noncyclic Chelating Scaffold for ⁸⁹Zr-Labeled ZEGFR:2377 Affibody Bioconjugates Targeting Epidermal Growth Factor Receptor Overexpression

Metal-Based Complexes as Pharmaceuticals for Molecular Imaging of the Liver

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Copper, gallium and zirconium positron emission tomography imaging agents: The importance of metal ion speciation

Cited by 55 publications

References 136 publications

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator

Cyclic versus Noncyclic Chelating Scaffold for 89Zr-Labeled ZEGFR:2377 Affibody Bioconjugates Targeting Epidermal Growth Factor Receptor Overexpression

Metal-Based Complexes as Pharmaceuticals for Molecular Imaging of the Liver

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Product

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About

Cyclic versus Noncyclic Chelating Scaffold for ⁸⁹Zr-Labeled ZEGFR:2377 Affibody Bioconjugates Targeting Epidermal Growth Factor Receptor Overexpression