Mechanically Interlocked Radiotracers Chelators for Efficient Cancer Therapy

Cancer is a leading global cause of death, with cases projected to rise sharply over the next decades. Radionuclide therapy (RNT) offers a highly selective alternative to conventional radiation treatments, using radiometal chelates for targeted tumour eradication. Despite clinical successes, current radiotracers face limitations including off-target toxicity, suboptimal pharmacokinetics, and insufficient stability. Mechanically Interlocked RAdiotracers CheLators (MIRACLEs) address these challenges by developing mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, as next-generation radiotracers. These structures enable modular synthesis, tunable dynamics, and stimulus-responsiveness, allowing “smart” tracers with enhanced protein targeting, biodistribution control and metabolic stability. By integrating DOTA/DO3A scaffolds within mechanically interlocked architectures, mechanical bonds decouple thermodynamic affinity from kinetic inertness, providing steric shielding and addressing a key failure mode of conventional radiochelates. This project will generate mechanically interlocked radiotracers (MIRTs) with improved in vivo stability, precise tissue-specific dosimetry, and efficient clearance. By combining supramolecular chemistry with radiopharmaceutical design, MIRACLE aims to deliver radiotheranostic agents with superior selectivity, safety and translational potential for clinical oncology.