Trithiols and their arsenic compounds for potential use in diagnostic and therapeutic radiopharmaceuticals

Introduction: Arsenic-72 (As-72; 2.49 MeV beta(+), 26 h) and As-77 (0.683 MeV beta(-), 38.8 h) have nuclear properties useful for positron emission tomography (PET) and radiotherapy applications, respectively. Their half-lives are sufficiently long for targeting tumors with antibodies, as well as peptides. Potential radiopharmaceuticals based on radioarsenic require development of suitable bifunctional chelates for stable conjugation of arsenic to vectors under in vivo conditions at high dilution. Methods: The thiophilic nature of arsenic led to the synthesis and characterization of a simple trithiol ligand and its arsenic complex, and radiolabeling studies at the no carrier added (NCA) As-77 level. Results: H-1- and C-13-NMR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and single crystal X-ray diffraction were used to characterize the trithiol ligand and its arsenic(III) complex. Radiotracer studies with no carrier added (NCA) As-77 resulted in high radiolabeling yields (>96%) with high in vitro stability. Conclusions: The high yield and stability of a single NCA As-77 trithiol complex indicates that this framework is suitable for developing matched pair agents for non-invasive in vivo PET imaging and radiotherapy of tumors with (72,77)AS. This is the first reported chelate developed for NCA radioarsenic and studies are underway for developing a trithiol bifunctional chelate conjugated to a targeting vector, such as a peptide or monodonal antibody. (C) 2016 Elsevier Inc. All rights reserved.