Early results in the irrational design of new bifunctional chelators

Chang, F.; Rusckowski, M.; Qu, Timothy; Hnatowich, Donald J.

doi:10.1002/(sici)1097-0142(19971215)80:12+<2347::aid-cncr3>3.3.co;2-m

Cited by 2 publications

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“…One interesting observation is that the use of side chains with electron donor atoms in thiol-containing peptide-based chelators (such as mercaptoacetyl-X-X or X-X-cys, where X are amino acids, Fig. (3) improves the labelling stability [107,108]. For example, the Affibody molecules demonstrated a lower accumulation of released pertechnetate in thyroid, stomach and salivary gland in the case of serine [109] or glutamic acid [110] instead of glycine in the mercaptoacetylcontaining chelating moiety.…”

Section: High Stability Of Radionuclide Coupling To the Targeting Pepmentioning

confidence: 99%

“…Such binding might be associated with the lipophilicity of a chelator or a linker. For example, Chang and co-workers [107] demonstrated that in mercaptoacetyl-containing peptide-based chelators for 99m Tc, the use of hydrophilic serine instead of glycine reduces the binding chelator-biotin to blood proteins three-fold. The substitution of glycine with more lipophilic phenylalanine caused a three-fold increase of blood protein binding.…”

Section: Rapid Clearance Of Non-reacted Targeting Protein From Blood mentioning

confidence: 99%

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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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Section: High Stability Of Radionuclide Coupling To the Targeting Pepmentioning

confidence: 99%

Section: Rapid Clearance Of Non-reacted Targeting Protein From Blood mentioning

confidence: 99%

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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“…Thus, we replaced the chelator in HYNIC-iPSMA with the more suitable mercaptoacetyltriserine, a classical N 3 S chelator suitable for 188 Re coordination ( Fig. 1 ) ( 11 , 12 ). In the following, we provide a summary of our research results thus far, including first-in-humans application under compassionate use.…”

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confidence: 99%

PSMA-GCK01: A Generator-Based^99mTc/¹⁸⁸Re Theranostic Ligand for the Prostate-Specific Membrane Antigen

et al. 2023

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Introduction: Prostate-specific membrane antigen (PSMA)-theranostic has been introduced with Gallium-68 and Lutetium-177, the currently most used radionuclides. However, Rhenium-188 is a well-known generator based therapeutic nuclide completing a theranostic tandem with Technetium-99m and may offer an interesting alternative to the current state of the art. In the present work, we aimed towards the development of a PSMA-targeted 99m Tc-/ 188 Re-theranostic tandem. Methods:The ligand HYNIC-iPSMA was chosen as lead structure. Its HYNIC chelator has limitations for 188 Re-labeling and was exchanged by MAS 3 to obtain PSMA-GCK01, as precursor for stable 99m Tc-and 188 Re-labeling. 99m Tc-PSMA-GCK01 was used for the in-vitro evaluation of the novel ligand and comparison with 99m Tc-EDDA/HYNIC-iPSMA. Planar imaging using 99m Tc-PSMA-GCK01 and organ biodistribution with 188 Re-PSMA-GCK01 were done using LNCaP-tumor bearing mice, respectively. Finally, the theranostic tandem was applied for imaging and therapy in three prostate cancer patients in compassionate care.Results: An efficient radiolabeling of PSMA-GCK01 with both radionuclides was demonstrated. Cell-based assays with 99m Tc-PSMA-GCK01 vs 99m Tc-EDDA/HYNIC-iPSMA revealed comparable uptake characteristics. Planar imaging and organ distribution revealed a good tumor uptake of both, 99m Tc-and 188 Re-PSMA-GCK01 at 1 h and 3 h p.i. with low uptake in non-target organs. In patients, similar distribution patterns were observed for 99m Tc-PSMA-GCK01 and 188 Re-PSMA-GCK01 and also in comparison of Tc/Re-PSMA-GCK01 with 177 Lu-PSMA-617. Conclusion:The novel ligand PSMA-GCK01 labels stable with 99m Tc-and 188 Re -both are generator based radionuclides -and, thus, provides access to on-demand labeling at reasonable costs. The preclinical evaluation of the compounds revealed favorable characteristics of the PSMA-targeted theranostic tandem. This result was further confirmed by a successful translation into first-in-human application.

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Early results in the irrational design of new bifunctional chelators

Abstract: The authors concluded that this simple synthesis and evaluation scheme may be used to prepare and screen a large library of bifunctional chelators for those with useful properties.

Cited by 2 publications

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

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

PSMA-GCK01: A Generator-Based^99mTc/¹⁸⁸Re Theranostic Ligand for the Prostate-Specific Membrane Antigen

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Early results in the irrational design of new bifunctional chelators

Abstract: The authors concluded that this simple synthesis and evaluation scheme may be used to prepare and screen a large library of bifunctional chelators for those with useful properties.

Cited by 2 publications

References 0 publications

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

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

PSMA-GCK01: A Generator-Based99mTc/188Re Theranostic Ligand for the Prostate-Specific Membrane Antigen

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PSMA-GCK01: A Generator-Based^99mTc/¹⁸⁸Re Theranostic Ligand for the Prostate-Specific Membrane Antigen