Abstract
Radiopharmaceuticals that combine diagnostic and therapeutic isotopes are at the forefront of novel cancer treatments. A crucial element is the method of attaching radioisotopes to biomolecules using chelator-based techniques that are widely used clinically. Selection from available chelators is essential because this choice influences the physicochemical and biological characteristics of the final radiopharmaceutical. Numerous chelators exist because none fulfill all ideal conditions: rapid and complete binding to radiometals at low concentrations and with metallic impurities, high thermodynamic and kinetic stability in vivo, easy bioconjugation, and, key for this work, achieving these for many radiometals from the growing list of medical isotopes. We demonstrate how nanotechnology may change this. Ten nano-radiotracers were synthesized, incorporating radiometals such as (68)Ga, (64)Cu, (89)Zr, (99m)Tc, (201)Tl, (111)In, (67)Ga, (177)Lu, (223)Ra, and (225)Ac into the nanoparticle core. The versatility of the platform was demonstrated through proof-of-concept experiments, including passive targeting in glioblastoma, active targeting of thrombosis, intratumoral radiotherapy in glioblastoma, and renal clearance optimization. This nanotracer addresses traditional challenges in radiopharmaceutical development, offering a single platform with consistent physicochemical and biological properties regardless of the radioisotope used for robust diagnostic and therapeutic applications.