Production of arsenic and antimony isotopes and their complexation with trithiol based chelators for radiopharmaceutical applications
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Radiopharmaceuticals contain radioactive nuclides, which decay and emit radiation for medical imaging or therapeutic purposes. Some radiopharmaceuticals have short half-life and impractical to deliver to remote locations for daily medical use. To address this challenge, radionuclide generators can be employed, enabling the on-site production of radionuclides. In this context, we focused on developing a 72Se/72As medical generator that can continuously supply 72As, a radionuclide useful for tumor imaging. Theranostic pairs, which combine therapeutic and diagnostic radionuclides, are of increasing interest for providing patients with the ability to diagnose and treat, through follow-up imaging. Antimony-119 is an Auger emitter, recently piqued the interest as a therapeutic agent but lacks the development of a diagnostic counterpart. Given the chemical similarities between arsenic (As) and antimony (Sb), we explored the potential of 72As as a diagnostic counterpart to create a theranostic pair with 119Sb for the first time. Arsenic-77 (0.683 MeVβ-max, t1/2: 38.8 h) and 72As (2.49 MeV β+max, t1/2: 26 h) are true theranostic matched pair. Previous research on 77As-labeled radiotracers targeting GRPR-positive cancer cells revealed high lipophilicity, which limited their effectiveness. To address this, the goal is to develop more hydrophilic 77As labeled radiotracers. Two trithiol bioconjugates were synthesized, attached to the RM2 peptide targeting GRP receptors, with modified linkers to increase hydrophilicity. One compound used a two serine linker, and the other used a glutamic acid-serine linker. The radiolabeling of these compounds, [77As]As-Glu-trithiol- (Ser)2-RM2 and [77As]As-Glu-trithiol-Glu-Ser-RM2, was optimized, and their in vitro stability and cell binding affinity were evaluated and compared.
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Ph. D.