Recent advancements in radiometal chelation for targeted applications in nuclear medicine.

In recent years, the rapid clinical advancement and expansion of nuclear imaging and therapy agents have (re)invigorated the field of radioisotope research due to progress and wider accessibility of radioisotope production. Many isotopes with decay properties suitable for imaging and therapy can be produced using low-energy cyclotrons; however, chemical labeling strategies enabling the incorporation of these isotopes into disease-/tissue-targeted radiopharmaceuticals are an active and rapidly expanding area of research. In this review, we survey key contemporary radiometal chelation strategies. One strategy encompasses the use of multifunctional, promiscuous azamacrocyclic chelators capable of binding divalent and trivalent radioactive isotopes for positron emission tomography, single-photon emission computed tomography, and radiotherapy with β- or α emitters of disparate sizes, charges, and chemical properties. The second strategy focuses on natural-product inspired and oxygen-rich approaches, capitalizing on their high affinity for biologically inert, high valent trivalent/tetravalent and pentavalent, oxophilic metal ions.