Cu(<scp>i</scp>)-assisted click chemistry strategy for conjugation of non-protected cross-bridged macrocyclic chelators to tumour-targeting peptides

Cai, Zhengxin; Li, Barbara T. Y.; Wong, Edward H.; Weisman, Gary R.; Anderson, Carolyn J.

doi:10.1039/c4dt03897e

Cited by 21 publications

(24 citation statements)

References 21 publications

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“…Consistent with the number of examples given, structures decoratedw ith alkyne functionalities ( Figure 4) [25][26][27][28][29][30] are encountered more frequently than those with azides ( Figure 5). Consistent with the number of examples given, structures decoratedw ith alkyne functionalities ( Figure 4) [25][26][27][28][29][30] are encountered more frequently than those with azides ( Figure 5).…”

Section: Azide-and Alkyne-decorated Bifunctional Chelatorsupporting

confidence: 71%

“…From al ogical point of view,t his provides severaldistinct options to be discussed: (1,2,3,8)t hat are commonly dubbed "protected chelators" or "prochelators" due to presence of tert-butyl ester protecting groups. Examples for alkyne-functionalized chelators (1 [25] ; 2, 8 [26] ; 3, 4 [27] ; 5 [28] ; 6 [29] ; 7 [30] ). To some extent, esterification can preventi nteractiono fC u II with the pendanta rm donor sites, although amide oxygens can also functiona sd onors here.…”

Section: Azide-and Alkyne-decorated Bifunctional Chelatormentioning

confidence: 99%

“…[29] Essentially,t he radiometal chelate herer epresents nothinge lse but ar adiolabeled prosthetic group, which puts this approach into the same perspectivea st he aforementioned click-radiofluorinations. [29] Essentially,t he radiometal chelate herer epresents nothinge lse but ar adiolabeled prosthetic group, which puts this approach into the same perspectivea st he aforementioned click-radiofluorinations.…”

Section: Demetalation:c U II Removalmentioning

confidence: 99%

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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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Section: Azide-and Alkyne-decorated Bifunctional Chelatorsupporting

confidence: 71%

Section: Azide-and Alkyne-decorated Bifunctional Chelatormentioning

confidence: 99%

Section: Demetalation:c U II Removalmentioning

confidence: 99%

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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 jack‐of‐all‐trades DOTA is suitable for all nuclides discussed, including 89 Zr, rendering DOTA‐conjugates quite universal radiometallation precursors despite their labeling kinetics as well as kinetic inertness are not optimal for many nuclides. Hence, tailored bifunctional chelators with superior radiolabeling properties and/or kinetic inertness have been identified for each individual metal, such as NOPO, HBED‐CC, DATA, and siderophors for 68 Ga, derivatives of cross‐bridged cyclam and sarcophagines for 64 Cu, cyclic or acyclic tetrahydroxamates and tetrahydroxypyridinones for 89 Zr, and lately AAZTA for 44 Sc . In summary, converting a bioactive molecule, eg, a peptide receptor ligand or antibody (‐fragment), into a radiometallated tracer is a comparably simple and straightforward endeavor …”

Section: Prospects Of Pet Radiometalsmentioning

confidence: 99%

Re‐thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals

Notni

Wester

2017

Labelled Comp Radiopharmac

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The potential and future role of certain metal radionuclides, for example, Sc, Zr, Y, Cu, Ga, Lu, Ac, and Bi, and several terbium isotopes has been controversially discussed in the past decades. Furthermore, the possible benefits of "matched pairs" of isotopes for tandem applications of diagnostics and therapeutics (theranostics) have been emphasized, while such approaches still have not made their way into routine clinical practice. Analysis of bibliographical data illustrates how popularity of certain nuclides has been promoted by cycles of availability and applications. We furthermore discuss the different practical requirements for diagnostic and therapeutic radiopharmaceuticals and the resulting consequences for efficient development of clinically useful pairs of radionuclide theranostics, with particular emphasis on the underlying economical factors. Based on an exemplary assessment of overall production costs for Ga and F radiopharmaceuticals, we venture a look into the future of theranostics and predict that high-throughput PET applications, that is, diagnosis of frequent conditions, will ultimately rely on F tracers. PET radiometals will occupy a niche in the clinical low-throughput sector (diagnosis of rare diseases), but above all, dominate preclinical research and clinical translation. Matched isotope pairs will be of lesser relevance for theranostics but may become important for future PET-based therapeutic dosimetry.

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“…While it is possible to conjugate the complex to the probe after radiolabelling, 18 this is typically not favoured as it results in a longer synthetic period overall. As such, high temperatures and extreme pH values are to be avoided.…”

Section: Mild Complexation Conditionsmentioning

confidence: 99%

Current advances in ligand design for inorganic positron emission tomography tracers ⁶⁸Ga, ⁶⁴Cu, ⁸⁹Zr and ⁴⁴Sc

2016

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A key part of the development of metal based Positron Emission Tomography probes is the chelation of the radiometal. In this review the recent developments in the chelation of four positron emitting radiometals, Ga,Cu, Zr andSc, are explored. The factors that effect the chelation of each radio metal and the ideal ligand system will be discussed with regards to high in vivo stability, complexation conditions, conjugation to targeting motifs and complexation kinetics. A series of cyclic, cross-bridged and acyclic ligands will be discussed, such as CP256 which forms stable complexes with Ga under mild conditions and PCB-TE2A which has been shown to form a highly stable complex withCu. Zr andSc have seen significant development in recent years with a number of chelates being applied to each metal - eight coordinate di-macrocyclic terephthalamide ligands were found to rapidly produce more stable complexes with Zr than the widely used DFO.

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Cu(i)-assisted click chemistry strategy for conjugation of non-protected cross-bridged macrocyclic chelators to tumour-targeting peptides

Cited by 21 publications

References 21 publications

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

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

Re‐thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals

Current advances in ligand design for inorganic positron emission tomography tracers ⁶⁸Ga, ⁶⁴Cu, ⁸⁹Zr and ⁴⁴Sc

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Cu(i)-assisted click chemistry strategy for conjugation of non-protected cross-bridged macrocyclic chelators to tumour-targeting peptides

Cited by 21 publications

References 21 publications

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

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

Re‐thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals

Current advances in ligand design for inorganic positron emission tomography tracers 68Ga, 64Cu, 89Zr and 44Sc

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Current advances in ligand design for inorganic positron emission tomography tracers ⁶⁸Ga, ⁶⁴Cu, ⁸⁹Zr and ⁴⁴Sc