Can a cysteine challenge assay predict the in vivo behavior of 99mTc-labeled antibodies?

Hnatowich, D.J.; Virzi, F.; Fogarasi, Miklos C.; Rusckowski, Mary; Winnard, Paul T.

doi:10.1016/0969-8051(94)90175-9

Cited by 42 publications

(20 citation statements)

References 9 publications

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“…The cysteine challenge is an empirical method of assessing the kinetic stability of complexes towards ligand exchange reactions, and is accepted as at least loosely indicative of in vivo kinetic stability of 99m Tc radiopharmaceuticals [33]. The concentration of cysteine in our assay was increased to increase the range of instability detected within 1 h of incubation.…”

Section: Discussionmentioning

confidence: 99%

Technetium-binding in labelled HYNIC-peptide conjugates: Role of coordinating amino acids

Surfraz

King

Mather

et al. 2009

Journal of Inorganic Biochemistry

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Section: Discussionmentioning

confidence: 99%

Technetium-binding in labelled HYNIC-peptide conjugates: Role of coordinating amino acids

Surfraz

King

Mather

et al. 2009

Journal of Inorganic Biochemistry

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“…The in vitro stability of 99m Tc-labeled affibody molecules was evaluated under four conditions: PBS, in the presence of 300-fold molar excess of cysteine (cysteine challenge) (Hnatowich et al 1994), and in the presence of ascorbic acid tin (II) chloride to prevent oxidation by air oxygen (Andersson et al 2016). For this purpose, samples of labeled and purified affibody molecules (2.2 µg, 50 µL) were mixed with either cysteine (12 µg, 1 mg/mL in PBS), sodium ascorbate (13 µg, 1 mg/mL in PBS) or SnCl 2 × 2H 2 O (10 µg, 1 mg/mL in 0.01 M HCl).…”

Section: Methodsmentioning

confidence: 99%

Influence of composition of cysteine-containing peptide-based chelators on biodistribution of 99mTc-labeled anti-EGFR affibody molecules

et al. 2018

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Epidermal growth factor receptor (EGFR) is overexpressed in a number of cancers and is the molecular target for several anti-cancer therapeutics. Radionuclide molecular imaging of EGFR expression should enable personalization of anti-cancer treatment. Affibody molecule is a promising type of high-affinity imaging probes based on a non-immunoglobulin scaffold. A series of derivatives of the anti-EGFR affibody molecule ZEGFR:2377, having peptide-based cysteine-containing chelators for conjugation of 99mTc, was designed and evaluated. It was found that glutamate-containing chelators Gly-Gly-Glu-Cys (GGEC), Gly-Glu-Glu-Cys (GEEC) and Glu-Glu-Glu-Cys (EEEC) provide the best labeling stability. The glutamate containing conjugates bound to EGFR-expressing cells specifically and with high affinity. Specific targeting of EGFR-expressing xenografts in mice was demonstrated. The number of glutamate residues in the chelator had strong influence on biodistribution of radiolabeled affibody molecules. Increase of glutamate content was associated with lower uptake in normal tissues. The 99mTc-labeled variant containing the EEEC chelator provided the highest tumor-to-organ ratios. In conclusion, optimizing the composition of peptide-based chelators enhances contrast of imaging of EGFR-expression using affibody molecules.Electronic supplementary materialThe online version of this article (10.1007/s00726-018-2571-1) contains supplementary material, which is available to authorized users.

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“…Though many of the chelates are both thermodynamically stable and kinetically inert, a complexation of a metal by a chelator is always a reversible process. At the same time, some blood plasma proteins, such as transferrin and ceruloplasmin, can chelate transitional metals and challenge a tracer labelled with 111 In, 67 Ga, 68 Ga, 64 Cu or 86 Y. Technetium chelates can be challenged by thiol-containing proteins [91]. For this reason, the stability of a particular combination of a nuclide and a chelator should be considered.…”

Section: High Stability Of Radionuclide Coupling To the Targeting Pepmentioning

confidence: 98%

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

Tolmachev

Orlova

2010

CMC

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Progress in genomics and proteomics provides clinical oncology with new anti-cancer drugs, which target selectively aberrantly expressed membrane proteins and associated signalling pathways in malignant cells. Molecular targeting also enables specific delivery of cytotoxic substances to tumours sparing healthy tissues. Improved selectivity of the treatment reduces side effects and widens the therapeutic window. However, only a part of the patients might benefit from such treatment due to inter- and intrapatient heterogeneity of therapeutic target expression. This makes it necessary to identify patients, who may benefit from targeting therapy. Radiolabelled peptides can provide selective and sensitive detection of molecular therapeutic targets in both primary tumours and metastases in a single non-invasive procedure, making personalised treatment possible. The choice of detection method (single photon emission tomography or positron emission tomography), radionuclide for labelling and labeling chemistry can appreciably influence the imaging property of a tracer. The labelling method might affect the binding affinity, the cellular processing and retention of a radionuclide, the biodistribution of a targeting peptide, and excretion pathways of a non-bound tracer and radiocatabolites. This influences the sensitivity and specificity of the imaging. This influence is exemplified by three classes of tumour-targeting peptides: somatostatin analogues, bombesin analogues and Affibody molecules. The review suggests approaches for selection of an optimal labelling chemistry.

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Can a cysteine challenge assay predict the in vivo behavior of 99mTc-labeled antibodies?

Cited by 42 publications

References 9 publications

Technetium-binding in labelled HYNIC-peptide conjugates: Role of coordinating amino acids

Technetium-binding in labelled HYNIC-peptide conjugates: Role of coordinating amino acids

Influence of composition of cysteine-containing peptide-based chelators on biodistribution of 99mTc-labeled anti-EGFR affibody molecules

Influence of Labelling Methods on Biodistribution and Imaging Properties of Radiolabelled Peptides for Visualisation of Molecular Therapeutic Targets

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