Combining three units of one of H-(alanyl)n-beta-(HO)alanyl peptides (n = 1-3) with nitrilotriacetic acid affords tripodal peptide hydroxamate ligands (1L, 1D, 2LL, 2DL, and 3LLL, where each L or D denotes the L- or D-alanyl residue). These ligands form six-coordinate octahedral complexes (Fe-1L, Fe-1D, Fe-2LL, Fe-2DL, and Fe-3LLL) with iron(III) in aqueous near neutral pH solution, and the stability and the chirality of the complexes formed depend on the alanyl residues incorporated. Thus Fe-2LL is the most stable against attack of H+ and OH- ions and the least labile in the iron(III) removal by EDTA. The CD spectra show a predominance of the A configuration for Fe-1D, Fe-2LL, Fe-2DL, and Fe-3LLL, but the opposite delta configuration for Fe-1L. These ligands and their gallium(III) complexes are studied by 1H NMR spectroscopy in DMSO-d6 solution. CD and NMR spectral analysis, aided by molecular model examinations, indicates that critical factors in controlling the configuration and the stability of the complexes are (1) the hydroxamate-carrying alanyl residue, (2) the expanse of an interior space in the ligand, and (3) an interstrand amide NH hydrogen bond; the latter bonding is possible with ligands 2LL and 2DL. A microbial growth promotion activity test shows that ligands 1L, 2LL, and 3LLL all act as iron-transporting agents.

No abstract

Hydroxypyridinones (HOPOs) have been used in the chelation therapy of iron and actinide metals. Their application in metal-based radiopharmaceuticals has also been increasing in recent years. This review article focuses on how multidentate HOPOs can be used in targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals. The general structure of radiometal-based targeted radiopharmaceuticals, a brief description of siderophores, the basic structure and properties of bidentate HOPO, some representative HOPO multidentate chelating agents, radiopharmaceuticals based on HOPO multidentate bifunctional chelators for gallium-68, thorium-227 and zirconium-89, as well as the future prospects of HOPO multidentate bifunctional chelators in other metal-based radiopharmaceuticals are described and discussed in turn. The HOPO metal-based radiopharmaceuticals that have shown good prospects in clinical and preclinical studies are gallium-68, thorium-227 and zirconium-89 radiopharmaceuticals. We expect HOPO multidentate bifunctional chelators to be a very promising platform for building novel targeted radiometal-based diagnostic and therapeutic radiopharmaceuticals.

No abstract

No abstract

No abstract

No abstract

C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or CD184, is a 7-transmembrane helix G-protein-coupled receptor that is encoded by the CXCR4 gene. Involved in various physiological processes, CXCR4 could form an interaction with its endogenous partner, chemokine ligand 12 (CXCL12), which is also named SDF-1. In the past several decades, the CXCR4/CXCL12 couple has attracted a large amount of research interest due to its critical functions in the occurrence and development of refractory diseases, such as HIV infection, inflammatory diseases, and metastatic cancer, including breast cancer, gastric cancer, and non-small cell lung cancer. Furthermore, overexpression of CXCR4 in tumor tissues was shown to have a high correlation with tumor aggressiveness and elevated risks of metastasis and recurrence. The pivotal roles of CXCR4 have encouraged an effort around the world to investigate CXCR4-targeted imaging and therapeutics. In this review, we would like to summarize the implementation of CXCR4-targeted radiopharmaceuticals in the field of various kinds of carcinomas. The nomenclature, structure, properties, and functions of chemokines and chemokine receptors are briefly introduced. Radiopharmaceuticals that could target CXCR4 will be described in detail according to their structure, such as pentapeptide-based structures, heptapeptide-based structures, nonapeptide-based structures, etc. To make this review a comprehensive and informative article, we would also like to provide the predictive prospects for the CXCR4-targeted species in future clinical development.