Abstract
AbstractMechanically interlocked molecules present opportunities to construct therapeutic drugs and diagnostic imaging agents but harnessing supramolecular chemistry to make biologically active probes in water is a challenge. Here, we describe a rotaxane‐based approach to synthesise radiolabelled proteins and peptides for molecular imaging of cancer biomarkers in vivo. Host–guest chemistry using β‐cyclodextrin‐ and cucurbit[6]uril‐catalysed cooperative capture synthesis produced gallium‐68 or zirconium‐89 radiolabelled metallo[4]rotaxanes. Photochemical conjugation to trastuzumab led to a viable positron emission tomography (PET) radiotracer. The rotaxane architecture can be tuned to accommodate different radiometal ion complexes, other protein‐ or peptide‐based drugs, and fluorophores for optical detection. This technology provides a platform to explore how mechanical bonding can improve drug delivery, enhance tumour specificity, control radiotracer pharmacokinetics, and reduce dosimetry.
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