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Synthesis and Evaluation of a Bifunctional Chelator for Thorium-227 Targeted Radiotherapy.
J Med Chem
January 2025
Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
Thorium-227 (Th) is an α-emitting radionuclide currently under investigation for targeted alpha therapy. Available chelators used for this isotope suffer from challenging multistep syntheses. Here, we present the synthesis and preclinical evaluation of a novel bifunctional chelator, SCN-Bn-DOTHOPO, which contains an isothiocyanate group that is suitable for conjugation to biological molecules.
View Article and Find Full Text PDFEnhancing the radionuclide theranostic concept through the radiohybrid approach.
RSC Med Chem
November 2024
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research Bautzner Landstraße 400 D-01328 Dresden Germany
Radionuclide theranostics - a fast-growing emerging field in radiopharmaceutical sciences and nuclear medicine - offers a personalised and precised treatment approach by combining diagnosis with specific and selective targeted endoradiotherapy. This concept is based on the application of the same molecule, labelled with radionuclides possessing complementary imaging and therapeutic properties, respectively. In radionuclide theranostics, radionuclide pairs consisting of the same element, such as Cu/Cu, Pb/Pb or I/I are of significant interest due to their identical chemical and pharmacological characteristics.
View Article and Find Full Text PDFComparative analysis of positron emitters for theranostic applications based on small bioconjugates highlighting Sc, Cu and Ti.
EJNMMI Phys
November 2024
Department of Nuclear Medicine, University Hospital of Bordeaux, Bordeaux, F-33076, France.
Background: Targeted radionuclide therapy with Lu-labelled small conjugates is expanding rapidly, and its success is linked to appropriate patient selection. Companion diagnostic conjugates are usually labelled with Ga, offering good imaging up to ≈2 h post-injection. However, the optimal tumor-to-background ratio is often reached later.
View Article and Find Full Text PDFPhosphonate-Based Aza-Macrocycle Ligands for Low-Temperature, Stable Chelation of Medicinally Relevant Rare Earth Radiometals and Radiofluorination.
J Am Chem Soc
December 2024
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
Radioisotopes of fluorine (F), scandium (Sc, Sc), lutetium (Lu), and yttrium (Y, Y) have decay properties ideally suited for targeted nuclear imaging and therapy with small biologics, such as peptides and antibody fragments. However, a single-molecule strategy to introduce these radionuclides into radiopharmaceuticals under mild conditions to afford inert in vivo complexes is critically lacking. Here, we introduce HL2 and HL3, two small-cavity macrocyclic chelator structural isomers bearing a single phosphonate functional group.
View Article and Find Full Text PDFTowards Optimal Automated Ga-Radiolabeling Conditions of the DOTA-Bisphosphonate BPAMD Without Pre-Purification of the Generator Eluate.
J Labelled Comp Radiopharm
December 2024
Nuclear Medicine Department, Institut Régional du Cancer de Montpellier (ICM), Université de Montpellier, Montpellier, France.
DOTA-functionalized bisphosphonates can be useful tools for PET imaging of bone metastases when radiolabeled with Ga. Moreover, the versatility of DOTA allows the complexation of radiometals with therapeutic applications (e.g.
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