2014;2:84C91. day.3 Owing to this epidemic threat, modern-day malignancy diagnostic and therapeutic approaches have been evolving rapidly. Particularly, a very powerful diagnostic method entails magnetic resonance imaging (MRI) in which metal-based contrast brokers are administered to improve image resolution. Chemotherapy, radiation therapy (XRT), and targeted therapy are some of the main types of malignancy therapy. Chemotherapy entails drugs to kill malignancy cells, while XRT uses high doses of radiation to eliminate tumors. Targeted therapy, as the name suggests, often uses small-molecule drugs or monoclonal antibodies to target specific proteins that drive malignancy cell proliferation. Small-molecule based drugs include inorganic compounds C most importantly the widely used cis-dichlorodiammineplatinum(II), better known as cisplatin. Indeed, metals are used extensively in malignancy diagnosis and therapy, and the lanthanides occupy an important market in these areas. Lanthanides are elements with atomic figures ranging from 57 (lanthanum) to 71 (lutetium). They also are known as rare earth elements, because they were once thought to be present in very small amounts in the Earth’s crust. However, we know today that lanthanides are relatively abundant. In 1803, the first lanthanide, cerium, was discovered in its mineral form C cerite.4 As lanthanides are extremely unstable when isolated in elemental form, they often are found as oxides and fluorides in rocks, ores, and minerals. As methods for the extraction and separation of these lanthanides salts continue to improve, many investigators have switched their attention toward utilizing these elements R-10015 in malignancy imaging and therapy. The redox stability of Ln3+ ions makes them highly suitable for cellular applications in the presence of biological reducing brokers like ascorbate and thiols, with the added advantage of favorable luminescent properties attributable to 4f?5d, charge-transfer, and f?f transitions.5 Currently, gadolinium-containing complexes C gadopentetic acid (Magnevist?) and gadoteric acid (Artirem?) C are commonly used R-10015 as MRI contrast brokers for malignancy imaging, 6 while lanthanide radioisotopes like 177Lu have been used in malignancy imaging and therapy.7 Other forms of lanthanides, such as lanthanide oxide nanoparticles, nanodrums, and nanocrystals are encouraging as imaging agents and potential anticancer drugs.8 For example, CeO2 nanoparticles (Nanoceria) are used to inhibit the deleterious effects of reactive oxygen intermediates and are under development as potential therapeutic Reln brokers.9 However, the biomedical applications of lanthanides lengthen well beyond their use as routine cancer therapeutics and imaging agents, and publications detailing their use have increased over the last 10 years (Determine 1). Our Perspective highlights current work as well as insights that could drive future applications for this class of metals in malignancy diagnosis and therapy C more specifically, we discuss recent developments in cytotoxic lanthanide brokers and inhibitors, photodynamic therapy (PDT), XRT, drug/gene delivery, biosensing, and bioimaging. In addition, elements such as yttrium whose properties are similar to those of the lanthanides will be included throughout. Open in a separate window Physique 1 Quantity of articles in on the topic lanthanide and malignancy from 2005 to 2015. 2. Cytotoxic Brokers and Inhibitors One of the earliest applications of lanthanides in malignancy therapy was reported by Anghileri and coworkers,10 who R-10015 emphasized the importance of cationic cell membrane interactions in mediating Ln cytotoxicity. Following this work, other lanthanide-based anticancer brokers were reported, with ones featuring complexation with a wide range of ligands, including hymecromone, umbelliferone, mendiaxon, warfarin, coumachlor and niffcoumar,.