Synthesis of C- and N-functionalised derivatives of 1,4,7-triazacyclononane-1,4,7-triyltriacetic acid (NOTA), 1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetrayltetra-acetic acid (DOTA), and diethylenenetriaminepenta-acetic acid (DTPA): bifunctional complexing agents for the derivatisation of antibodies

Cox, Jonathan P.L.; Craig, Andrew S.; Helps, I. M.; Jankowski, Karl J.; Parker, David; Eaton, Michael A. W.; Millican, Andrew T.; Millar, Kenneth; Beeley, N. R. A.; Boyce, Byron A.

doi:10.1039/p19900002567

Cited by 82 publications

(49 citation statements)

References 10 publications

(4 reference statements)

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“…This chelate was rapidly coupled to D-Phe-NH 2 as a model peptide which renders the coupling of 68 Ga(NODASA) to peptides that are promising for PET applications (49). (50)(51)(52). Their approaches included intra-or intermolecular cyclization strategy as key steps, affording NOTAs functionalized on a carbon of the macrocyclic ring.…”

Section: Chelators and Coupling Chemistrymentioning

confidence: 99%

⁶⁸Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

Fani

André

Maecke

2008

Contrast Media & Molecular

300

318

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PET (positron emission tomography) is a powerful diagnostic and imaging technique which requires short-lived positron emitting isotopes. The most commonly used are accelerator-produced (11)C and (18)F. An alternative is the use of metallic positron emitters. Among them (68)Ga deserves special attention because of its availability from long-lived (68)Ge/(68)Ga generator systems which render (68)Ga radiopharmacy independent of an onsite cyclotron. The coordination chemistry of Ga(3+) is dominated by its hard acid character. A variety of mono- and bifunctional chelators have been developed which allow the formation of stable (68)Ga(3+)complexes and convenient coupling to biomolecules. (68)Ga coupling to small biomolecules is potentially an alternative to (18)F- and (11)C-based radiopharmacy. In particular, peptides targeting G-protein coupled receptors overexpressed on human tumour cells have shown preclinically and clinically high and specific tumour uptake. Kit-formulated precursors along with the generator may be provided, similar to the (99)Mo/(99m)Tc-based radiopharmacy, still the mainstay of nuclear medicine.

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Section: Chelators and Coupling Chemistrymentioning

confidence: 99%

⁶⁸Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

Fani

André

Maecke

2008

Contrast Media & Molecular

300

318

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“…The tetrahydrochloride salt of (S)-4-(1,4,7-triazacyclononane-2-yl)butan-1-amine 21 confirmed the enantiomeric purity to be > 97%. 22,24 Tert …”

Section: (S)-tert-butyl 4-(147-triazacyclononane-2-yl)butylcarbamatementioning

confidence: 88%

Synthesis of meta and para-substituted aromatic sulfonate derivatives of polydentate phenylazaphosphinate ligands: enhancement of the water solubility of emissive europium(iii) EuroTracker® dyes

2014

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Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. Results and DiscussionThe target complexes ( Fig. 1) include three strongly absorbing and equivalent chromophores, in which there is meta or para-sulfonic acid substituent in the phenyl ring of the phosphinate moiety. The sulfonation of this position was not expected to perturb the chromophore characteristics significantly, as the phosphorus oxygen bond and the aryl groups to which it is attached are not strongly conjugated, unlike a trigonal amide or carboxylate substituent.Previous X-ray analysis studies of these phenylphosphinate lanthanide complexes have revealed that the phenyl rings are oriented in the same direction, away from the plane of the 9-N 3 ring, and with the same relative configuration at phosphorus. 13,15,16 These structural studies also confirmed that the phosphorus-oxygen double bond lies out of the plane of the aryl rings. A simple retrosynthetic analysis suggests the intermediacy of a 2,4,6-trisubstituted pyridine, with a 4-Br group, allowing a Sonogashira coupling reaction to an arylalkyne in a final ligand assembly step. the P centres respectively, as deduced by X-ray and CD studies on related systems. [13][14][15][16] OBC 2014 Delbianco 3In order to form the C-P bond, a palladium-catalysed reaction was envisaged, allowing insertion of a 2-pyridyl group into the P-H bond of a phenylphosphinic ester, bearing a suitably protected sulfonate group. Following the studies of Miller, 6a the behaviour of the trifluoroethyl and phenylsulfonate esters as protecting groups for the sulfonic acid moiety was examined; each ester was derived from 3 or 4-bromo-phenylsulfonyl chloride (Scheme 1).Palladium-catalysed coupling between the aryl bromide and anilinium hypophosphite proceeded in 70% yield for the trifluoroethyl ester, but failed with the phenyl ester, probably due to competitive insertion into the O-Ph bond. In this reaction, the added aminopropyltriethoxysilane serves as a base in the Pd-catalysed reaction, and enables the esterification of the phosphinic acid in situ. 17-19 Scheme 1The di-esters 3 and 4 were used in coupling reactions with 2-bromo-4-nitro-6-methyl pyridine in degassed toluene using Cl 2 Pd[bis(diphenylphosphino)ferrocene] as the catalyst to give the phosphinate esters 5 and 6 (Scheme 2). Bromination with neat acetyl bromide followed by reesterification of the phosphinic acid group with HC(OEt) 3 allowed the isolation of intermediates 7 and 8 in 77 and 81 % yield respectively. Treatme...

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“…The incorporation of chelators might alter the size, surface charge, and hydrophilicity of the tracers, which may eventually lead to completely different imaging consequences. [4] In addition, due to their macrocyclic structure and relatively hydrophobic nature, [5] chelators might also interact with nanoparticles, influencing the overall imaging results. Therefore, although chelators have been widely employed in PET imaging of nanomaterials in the past decade, it is still questionable whether such a practice is precise enough to depict their real biodistribution.…”

Section: Graphical Abstractmentioning

confidence: 99%

Chelator‐Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation

et al. 2017

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Macrocyclic chelators have been widely employed in the realm of nanoparticle-based positron emission tomography (PET) imaging, whereas its accuracy remains questionable. Here, we found that 64 Cu can be intrinsically labeled onto nanographene based on interactions between Cu and the π electrons of graphene without the need of chelator conjugation, providing a promising alternative radiolabeling approach that maintains the native in vivo pharmacokinetics of the nanoparticles. Due to abundant π bonds, reduced graphene oxide (RGO) exhibited significantly higher labeling efficiency in comparison with graphene oxide (GO) and exhibited excellent radiostability in vivo. More importantly, nonspecific attachment of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) on nanographene was observed, which revealed that chelator-mediated nanoparticle-based PET imaging has its inherent drawbacks and can possibly lead to erroneous imaging results in vivo. Graphical abstractChelator-free radiolabeling based on interactions between Cu and the π electrons of nanographene was shown, which can potentially substitute chelator-assisted labeling. The reliability of in vivo positron emission tomography imaging is enhanced while bypassing the inherent drawbacks of conventional chelator-based labeling. Macrocyclic chelators, such as DOTA (1,4,7,10-tetraazacy-clododecane-1,4,7,10-tetraacetic acid) or NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), have been routinely employed for small molecule and antibody-based positron emission tomography (PET), offering sensitive, quantitative and non-invasive functional detection of diseases at cellular or molecular levels. [1] In the past decade, with the explosive advances in nanotheranostic research, chelator conjugation has been expanded to the realm of nanoparticle-based PET imaging, [2] which has assisted in the evaluation of new nanoparticles by better understanding their in vivo biodistribution. Owing to the numerous reports of successful nanoparticle-based PET imaging employing macrocyclics-aided radiometal chelation, [3] it is now considered as the gold standard in PET-based evaluation of nanoparticle kinetics. However, chelator-based radiolabeling and PET imaging have their inevitable challenges. The incorporation of chelators might alter the size, surface charge, and hydrophilicity of the tracers, which may eventually lead to completely different imaging consequences. [4] In addition, due to their macrocyclic structure and relatively hydrophobic nature, [5] chelators might also interact with nanoparticles, influencing the overall imaging results. Therefore, although chelators have been widely employed in PET imaging of nanomaterials in the past decade, it is still questionable whether such a practice is precise enough to depict their real biodistribution.To better understand the in vivo behavior of the nanoparticles and avoid the influence of the chelators, a novel chelator-free radiolabeling approach can be employed, whereby radiometals can directly label onto the nano...

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Cited by 82 publications

References 10 publications

⁶⁸Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

⁶⁸Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

Synthesis of meta and para-substituted aromatic sulfonate derivatives of polydentate phenylazaphosphinate ligands: enhancement of the water solubility of emissive europium(iii) EuroTracker® dyes

Chelator‐Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation

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Cited by 82 publications

References 10 publications

68Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

68Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

Synthesis of meta and para-substituted aromatic sulfonate derivatives of polydentate phenylazaphosphinate ligands: enhancement of the water solubility of emissive europium(iii) EuroTracker® dyes

Chelator‐Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation

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⁶⁸Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

⁶⁸Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals