Chelators and metal complex stability for radiopharmaceutical applications

Okoye, Nkemakonam C.; Baumeister, Jakob E.; Khosroshahi, Firouzeh Najafi; Hennkens, Heather M.; Jurisson, Silvia S.

doi:10.1515/ract-2018-3090

Cited by 41 publications

(51 citation statements)

References 197 publications

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“…Moreover, a lipophilic character of the tracer can increase nonspecific uptake in other organs. 20 , 22 − 24 , 28 In the case of PSMA ligands, higher ligand lipophilicity of PSMA-I&T-based ligands led to an increase in tumor uptake in LNCaP xenografts. 24 In addition, Böhmer et al developed and characterized a copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) based PSMA ligand for PET imaging called [ 18 F]PSMA-MIC01.…”

Section: Discussionmentioning

confidence: 99%

Strain-Promoted Azide–Alkyne Cycloaddition-Based PSMA-Targeting Ligands for Multimodal Intraoperative Tumor Detection of Prostate Cancer

et al. 2021

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Strain-promoted azide–alkyne cycloaddition (SPAAC) is a straightforward and multipurpose conjugation strategy. The use of SPAAC to link different functional elements to prostate-specific membrane antigen (PSMA) ligands would facilitate the development of a modular platform for PSMA-targeted imaging and therapy of prostate cancer (PCa). As a first proof of concept for the SPAAC chemistry platform, we synthesized and characterized four dual-labeled PSMA ligands for intraoperative radiodetection and fluorescence imaging of PCa. Ligands were synthesized using solid-phase chemistry and contained a chelator for 111 In or 99m Tc labeling. The fluorophore IRDye800CW was conjugated using SPAAC chemistry or conventional N -hydroxysuccinimide (NHS)–ester coupling. Log D values were measured and PSMA specificity of these ligands was determined in LS174T-PSMA cells. Tumor targeting was evaluated in BALB/c nude mice with subcutaneous LS174T-PSMA and LS174T wild-type tumors using μSPECT/CT imaging, fluorescence imaging, and biodistribution studies. SPAAC chemistry increased the lipophilicity of the ligands (log D range: −2.4 to −4.4). In vivo , SPAAC chemistry ligands showed high and specific accumulation in s.c. LS174T-PSMA tumors up to 24 h after injection, enabling clear visualization using μSPECT/CT and fluorescence imaging. Overall, no significant differences between the SPAAC chemistry ligands and their NHS-based counterparts were found (2 h p.i., p > 0.05), while 111 In-labeled ligands outperformed the 99m Tc ligands. Here, we demonstrate that our newly developed SPAAC-based PSMA ligands show high PSMA-specific tumor targeting. The use of click chemistry in PSMA ligand development opens up the opportunity for fast, efficient, and versatile conjugations of multiple imaging moieties and/or drugs.

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Section: Discussionmentioning

confidence: 99%

Strain-Promoted Azide–Alkyne Cycloaddition-Based PSMA-Targeting Ligands for Multimodal Intraoperative Tumor Detection of Prostate Cancer

et al. 2021

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“…193,194,195 Since radioactive rhenium isotopes have found applications in radiochemistry, few complexes have been applied in nuclear medicine. 196,197 They also are used as analogues of potential Tc-99m diagnostic imaging agents for Alzheimer's disease. 198 It seemed natural that the incorporation of NHC ligands for this purpose should be studied.…”

Section: B) Technetium and Rheniummentioning

confidence: 99%

Recent progress on NHC-stabilized early transition metal (group 3–7) complexes: Synthesis and applications

Romain

Bellemin‐Laponnaz

Dagorne

2020

Coordination Chemistry Reviews

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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“…A number of new site-specific conjugation techniques to mAbs are also being developed [ 38 ]. Chelating agents for radiometal isotopes and their attachment to biomolecules have been extensively reviewed [ 39 , 40 , 41 , 42 ]. The selected chelating agent needs to bind the selected radionuclide with high thermodynamic stability and kinetic inertness to ensure high stability of the complex in vivo [ 30 ].…”

Section: Nuclear Molecular Imaging and Trt Using Tkismentioning

confidence: 99%

“…Attachment of chelators to biomolecules is generally carried out through a nucleophilic reaction of a bifunctional chelating agent with an available primary amine [ 39 , 40 ]. The structures of most SM TKIs do not have free amines (primary or secondary) available for functionalization since the amines are in positions where they are required for binding to the TK active site.…”

Section: Selection and Radiolabeling Of New Tkis For Trt Of Gbmentioning

confidence: 99%

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

et al. 2021

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Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

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Chelators and metal complex stability for radiopharmaceutical applications

Cited by 41 publications

References 197 publications

Strain-Promoted Azide–Alkyne Cycloaddition-Based PSMA-Targeting Ligands for Multimodal Intraoperative Tumor Detection of Prostate Cancer

Strain-Promoted Azide–Alkyne Cycloaddition-Based PSMA-Targeting Ligands for Multimodal Intraoperative Tumor Detection of Prostate Cancer

Recent progress on NHC-stabilized early transition metal (group 3–7) complexes: Synthesis and applications

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

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