Measurement of the rate of copper(II) exchange for 64Cu complexes of bifunctional chelators

Maheshwari, Vidhi; Dearling, Jason; Treves, S. Ted; Packard, Alan B.

doi:10.1016/j.ica.2012.07.012

Cited by 60 publications

(66 citation statements)

References 30 publications

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“…The experimental procedure was slightly modified from the previous report. 34 In short, PCB-TE1A1P and DOTA were radiolabeled with 64 Cu ions at 90°C, and the Cu(II) exchange experiment was performed at body temperature of 37°C…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for ⁶⁴Cu Radiotracers

Dale

Pandya

et al. 2015

Inorg. Chem.

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Bifunctional chelators have been successfully used to construct (64)Cu-labeled radiopharmaceuticals. Previously reported chelators with cross-bridged cyclam backbones have various essential features such as high stability of the copper(II) complex, high efficiency of radiolabeling at room temperature, and good biological inertness of the radiolabeled complex, along with rapid body clearance. Here, we report a new generation propylene-cross-bridged chelator with hybrid acetate/phosphonate pendant groups (PCB-TE1A1P) developed with the aim of combining these key properties in a single chelator. The PCB-TE1A1P was synthesized from cyclam with good overall yield. The Cu(II) complex of our chelator showed good robustness in kinetic stability evaluation experiments, such as acidic decomplexation and cyclic voltammetry studies. The Cu(II) complex of PCB-TE1A1P remained intact under highly acidic conditions (12 M HCl, 90 °C) for 8 d and showed quasi-reversible reduction/oxidation peaks at -0.77 V in electrochemical studies. PCB-TE1A1P was successfully radiolabeled with (64)Cu ions in an acetate buffer at 60 °C within 60 min. The electrophoresis study revealed that the (64)Cu-PCB-TE1A1P complex has net negative charge in aqueous solution. The biodistribution and in vivo stability study profiles of (64)Cu-PCB-TE1A1P indicated that the radioactive complex was stable under physiological conditions and cleared rapidly from the body. A whole body positron emission tomography (PET) imaging study further confirmed high in vivo stability and fast clearance of the complex in mouse models. In conclusion, PCB-TE1A1P has good potential as a bifunctional chelator for (64)Cu-based radiopharmaceuticals, especially those involving peptides.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for ⁶⁴Cu Radiotracers

Dale

Pandya

et al. 2015

Inorg. Chem.

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“…www.chemeurj.org NOTA( 1,4,7-triazacyclononane-1,4,7-triacetic acid) was found to be ab etter choice than EDTA, because it is more soluble in water at acidic pH, its Cu II complexi sc onsiderably more stable (log K ML = 22.4), [33] and Cu II complexation kinetics even at pH 2 are sufficiently fast. [47] Notwithstanding this, CuAACc oupling of alkyne-functionalized [Gd III (DOTA)] units to various substrates, for example to the ubiquitous cyclo(RGDfK) peptide (Figure 9), has been performed without complications. The reactionc onditions (moderately acidic aqueous mediaa nd room temperature or mild heating) are compatible with ab road array of applications;i nf act, they are less offensive than standard peptide deprotectionsw ith TFA.…”

Section: Demetalation:c U II Removalmentioning

confidence: 99%

A Practical Guide on the Synthesis of Metal Chelates for Molecular Imaging and Therapy by Means of Click Chemistry

Notni

Wester

2016

Chemistry A European J

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The copper-catalyzed cycloaddition of organic azides and alkynes (CuAAC) is one of the most popular reactions for rapid assembly of multifunctional molecular frameworks from commercially available building blocks. It is also attractive for synthesis of conjugates of multidentate chelate ligands (chelators) with molecular targeting vectors, such as peptides or proteins, which serve as precursors for labeling with metal radionuclides or are useful as MRI contrast agents after Gd(III) complexation. However, applicability of CuAAC for such purposes is complicated by formation of unwanted copper chelates. The alternative use of copper-free click chemistry, for example, the strain-promoted alkyne-azide cycloaddition (SPAAC) or the Diels-Alder reaction of tetrazines and strained alkenes, entails other specific challenges: Introduction of large, isomerically non-homogeneous and hydrophobic linker groups affects product homogeneity and can severely change pharmacokinetic profiles. Against this background, this review elucidates scope and applicability of both Cu-catalyzed and Cu-free alkyne-azide cycloadditions pertinent to the elaboration of radiometal chelates and MRI contrast agents, with an emphasis on strategies to tackle the problem of copper complexation during CuAAC.

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“…However, the labelling step should be rapid, efficient, and not require demanding purification steps. Moreover, to achieve exact quantitative biodistribution and pharmacokinetic data, it should be ensured that the radioisotope binds to the BFCA strongly as any radiometal leakage in living systems will lead to inaccurate determinations …”

Section: Radiopharmaceutical Chelatesmentioning

confidence: 99%

Harnessing the Coordination Chemistry of 1,4,7‐Triazacyclononane for Biomimicry and Radiopharmaceutical Applications

et al. 2018

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1,4,7‐Triazacyclononane (TACN)‐based mono‐ and poly‐nuclear metal complexes have found extensive use as biological mimics for understanding the structural and operational aspects of complex natural systems. Their coordination flexibility has also provided researchers access to a vast library of radiometal‐binding motifs that display excellent thermodynamic stability and kinetic inertness upon metal complexation. Synthetic modification of the TACN backbone has yielded ligands that can form metal complexes with coordination geometries well suited for these applications. In particular, Leone Spiccia's research has played a significant role in accelerating the progress in these two fields. With a focus on his contributions to the topics of biomimicry and radiopharmaceuticals, this Minireview uses relevant examples to put in perspective the utility of macrocyclic coordination chemistry for biological inorganic chemistry applications.

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Measurement of the rate of copper(II) exchange for 64Cu complexes of bifunctional chelators

Cited by 60 publications

References 30 publications

Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for ⁶⁴Cu Radiotracers

Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for ⁶⁴Cu Radiotracers

A Practical Guide on the Synthesis of Metal Chelates for Molecular Imaging and Therapy by Means of Click Chemistry

Harnessing the Coordination Chemistry of 1,4,7‐Triazacyclononane for Biomimicry and Radiopharmaceutical Applications

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Measurement of the rate of copper(II) exchange for 64Cu complexes of bifunctional chelators

Cited by 60 publications

References 30 publications

Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for 64Cu Radiotracers

Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for 64Cu Radiotracers

A Practical Guide on the Synthesis of Metal Chelates for Molecular Imaging and Therapy by Means of Click Chemistry

Harnessing the Coordination Chemistry of 1,4,7‐Triazacyclononane for Biomimicry and Radiopharmaceutical Applications

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Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for ⁶⁴Cu Radiotracers

Synthesis and Evaluation of New Generation Cross-Bridged Bifunctional Chelator for ⁶⁴Cu Radiotracers