CXCR4-Targeted Radiopharmaceuticals for the Imaging and Therapy of Malignant Tumors.

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.

Hydroxypyridinones as a Very Promising Platform for Targeted Diagnostic and Therapeutic Radiopharmaceuticals.

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.

Integrin αvß3 receptor targeting PET/MRI dual-modal imaging probe based on the 64Cu labeled manganese ferrite nanoparticles.

With the advent of positron emission tomography/magnetic resonance imaging (PET/MRI) scanner, PET/MRI dual-modal imaging will play more and more important role in the diagnosis of cancers and other diseases. Until now, there is no an approved PET/MRI dual-modal imaging probe. The goal of this work is to design and synthesize potential PET/MRI dual-modal imaging probe based on superparamagnetic manganese ferrite nanoparticles. We have developed superparamagnetic nanoparticles that have uniform size with 5 nm and can be further functionalized through surface coating with dopamine and polyethylene glycol derivatives, which provide functional groups for conjugating tumor-targeting biomolecules and bifunctional chelators. The nanoparticles conjugated with integrin αvß3 over-expressed targeting cyclic arginine-glycine-aspartic acid (RGD)-peptide and labeled with positron radionuclide copper-64 were intravenously injected into glioblastoma xenograft nude mice. In vivo MRI and PET imaging of mice implied that the PET/MRI dual-modal imaging probe can precisely locate the tumor site with αvß3 over expression.

Anti-tumor activities of four chelating agents against human neuroblastoma cells.

BACKGROUND: Iron deprivation may be a therapeutic strategy for cancer. It can be achieved by using iron chelators. In this investigation, anti-neuroblastoma activities of a novel ferric chelator 2LL together with DFO, EDTA and DTPA were evaluated. MATERIALS AND METHODS: SH-Sy5y cells were cultured at 37 degrees C in 5% CO2/95% air in DMEM containing 10% fetal bovine serum. The cells were seeded in 96-well microtiter plates overnight. Then, chelating agents were added into the wells. After 48-hour incubation, viabilities were measured using the MTT method. RESULTS: DTPA had an IC50 value between 60-100 microM; DFO produced about 40% inhibiting effect at 150 microM; 2LL and EDTA displayed about 10% inhibiting effect at high concentrations. CONCLUSION: For SH-Sy5y cells, DTPA showed the strongest inhibiting effect, DFO displayed a moderate inhibiting effect, while 2LL and EDTA produced minor inhibition. To develop iron chelators as powerful anti-cancer agents is still a challenging task.