Abstract::
Targeted Radionuclide Therapies (TRTs) based on Auger emitting radionuclides have the potential to deliver
extremely selective therapeutic payloads on the cellular level. However, to fully exploit this potential, suitable
radionuclides need to be applied in combination with appropriate delivery systems. In this review, we summarize the
state-of-the-art in production, purification, chelation and applications of two promising candidates for Targeted Auger
Therapy, namely antimony-119 (119Sb) and mercury-197 (197Hg). Both radionuclides have great potential to become
efficient tools for TRT. We also highlight our current progress on the production of both radionuclides at TRIUMF and
the University of Wisconsin.
Mercury‐197 m/g are a promising pair of radioactive isomers for incorporation into a theranostic as they can be used as a diagnostic agent using SPECT imaging and a therapeutic via Meitner‐Auger electron emissions. However, the current absence of ligands able to stably coordinate 197m/gHg to a tumour‐targeting vector precludes their use in vivo. To address this, we report herein a series of sulfur‐rich chelators capable of incorporating 197m/gHg into a radiopharmaceutical. 1,4,7,10‐Tetrathia‐13‐azacyclopentadecane (NS4) and its derivatives, (2‐(1,4,7,10‐tetrathia‐13‐azacyclopentadecan‐13‐yl)acetic acid (NS4‐CA) and N‐benzyl‐2‐(1,4,7,10‐tetrathia‐13‐azacyclopentadecan‐13‐yl)acetamide (NS4‐BA), were designed, synthesized and analyzed for their ability to coordinate Hg2+ through a combination of theoretical (DFT) and experimental coordination chemistry studies (NMR and mass spectrometry) as well as 197m/gHg radiolabeling studies and in vitro stability assays. The development of stable ligands for 197m/gHg reported herein is extremely impactful as it would enable their use for in vivo imaging and therapy, leading to personalized treatments for cancer.
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