PSMA-targeted low-molecular double conjugates for diagnostics and therapy

Petrov, Stanislav A.; Zyk, Nikolay Y.; Machulkin, Aleksei E.; Белоглазкина, Е. К.; Majouga, Alexander G.

doi:10.1016/j.ejmech.2021.113752

Cited by 9 publications

(13 citation statements)

References 152 publications

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“…One of the notable breakthroughs was the first-in-human PET imaging with a 68 Ga-labeled PSMAtargeting agent, [ 68 Ga]Ga-PSMA-11 ([ 68 Ga]PSMA-HBED-CC or [ 68 Ga]DKFZ-PSMA-11 in the literature), reported by the German Cancer Research Center and the University Hospital Heidelberg [44]. This agent is composed of three components: (1) a PSMAtargeting peptidomimetic moiety, Lys-urea-Glu (Lys-u-Glu), (2) an Ahx spacer, and (3) a chelator for 68 Ga-labeling, HBED-CC. The HBED-CC chelator, which contains an aminephenol backbone, binds strongly with Ga(III).…”

Section: Small Molecule Inhibitors/ligands Of Psmamentioning

confidence: 99%

“…Given that the current development of the agents has shifted towards the systematic chemical modifications of the linkage between the targeting moiety and theranostic payloads, this review also provides an overview of critical structural determinants of the chemical modifications for the development of next generation PSMA-targeting agents. Of note, many recent review articles are valuable for covering the applications of PSMA-targeted imaging and therapy [2][3][4][5][6].…”

Section: Introduction 1prostate-specific Membrane Antigen (Psma) and Psma-targeting Agentsmentioning

confidence: 99%

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PSMA-Targeting Imaging and Theranostic Agents—Current Status and Future Perspective

Debnath

Zhou

McLaughlin

et al. 2022

IJMS

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In the past two decades, extensive efforts have been made to develop agents targeting prostate-specific membrane antigen (PSMA) for prostate cancer imaging and therapy. To date, represented by two recent approvals of [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL by the United States Food and Drug Administration (US-FDA) for positron emission tomography (PET) imaging to identify suspected metastases or recurrence in patients with prostate cancer, PSMA-targeting imaging and theranostic agents derived from small molecule PSMA inhibitors have advanced to clinical practice and trials of prostate cancer. The focus of current development of new PSMA-targeting agents has thus shifted to the improvement of in vivo pharmacokinetics and higher specific binding affinity with the aims to further increase the detection sensitivity and specificity and minimize the toxicity to non-target tissues, particularly the kidneys. The main strategies involve systematic chemical modifications of the linkage between the targeting moiety and imaging/therapy payloads. In addition to a summary of the development history of PSMA-targeting agents, this review provides an overview of current advances and future promise of PSMA-targeted imaging and theranostics with focuses on the structural determinants of the chemical modification towards the next generation of PSMA-targeting agents.

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Section: Small Molecule Inhibitors/ligands Of Psmamentioning

confidence: 99%

Section: Introduction 1prostate-specific Membrane Antigen (Psma) and Psma-targeting Agentsmentioning

confidence: 99%

PSMA-Targeting Imaging and Theranostic Agents—Current Status and Future Perspective

Debnath

Zhou

McLaughlin

et al. 2022

IJMS

View full text Add to dashboard Cite

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“…The thermodynamic stability of metal complexes is usually expressed in terms of the thermodynamic stability constant (KML, formulated in Equations (1) and (2)). A high thermodynamic stability constant (LogKML > 18) indicates that the complex formed is a stable complex [ 105 , 106 ].…”

Section: Bifunctional Chelator Used In Radiopharmaceutical Agentsmentioning

confidence: 99%

“…DTPA (diethylenetriaminepentaacetic acid) is an octadentate polyaminocarboxylate acyclic chelator which has long been used in the radiopharmaceutical field. DTPA coordinates with radionuclides such as 111 In, 90 Y, 177 Lu, 64 Cu, and 68 Ga ( Table 4 ) by five oxygen donor atoms resulting from deprotonation of the carboxylate group and three nitrogen donor atoms from tertiary amine groups [ 106 ]. Like other acyclic BFCAs, DTPA forms a complex with radionuclide at room temperature (25 °C) and pH 4.5–5.5 for several minutes (about 5–20 min), generating stable complexes with radionuclides expessed by higher LogK ML (see Table 4 ) [ 105 , 106 , 109 ].…”

Section: Bifunctional Chelator Used In Radiopharmaceutical Agentsmentioning

confidence: 99%

“…DTPA coordinates with radionuclides such as 111 In, 90 Y, 177 Lu, 64 Cu, and 68 Ga ( Table 4 ) by five oxygen donor atoms resulting from deprotonation of the carboxylate group and three nitrogen donor atoms from tertiary amine groups [ 106 ]. Like other acyclic BFCAs, DTPA forms a complex with radionuclide at room temperature (25 °C) and pH 4.5–5.5 for several minutes (about 5–20 min), generating stable complexes with radionuclides expessed by higher LogK ML (see Table 4 ) [ 105 , 106 , 109 ]. Acyclic BFCAs have problems in vivo stability due to dissociation and transchelation of radiometal complexes.…”

Section: Bifunctional Chelator Used In Radiopharmaceutical Agentsmentioning

confidence: 99%

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The Chemical Scaffold of Theranostic Radiopharmaceuticals: Radionuclide, Bifunctional Chelator, and Pharmacokinetics Modifying Linker

et al. 2022

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Therapeutic radiopharmaceuticals have been researched extensively in the last decade as a result of the growing research interest in personalized medicine to improve diagnostic accuracy and intensify intensive therapy while limiting side effects. Radiometal-based drugs are of substantial interest because of their greater versatility for clinical translation compared to non-metal radionuclides. This paper comprehensively discusses various components commonly used as chemical scaffolds to build radiopharmaceutical agents, i.e., radionuclides, pharmacokinetic-modifying linkers, and chelators, whose characteristics are explained and can be used as a guide for the researcher.

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