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The ability to append targeting biomolecules to chelators that efficiently coordinate to the diagnostic imaging radionuclide, Tc, and the therapeutic radionuclide, Re, can potentially enable receptor-targeted "theranostic" treatment of disease. Here we show that Pt(0)-catalyzed hydrophosphination reactions are well-suited to the derivatization of diphosphines with biomolecular moieties enabling the efficient synthesis of ligands of the type PhPCHCHP(CHCH-Glc) (, where Glc = a glucose moiety) using the readily accessible PhPCHCHPH and acryl derivatives. It is shown that hydrophosphination of an acrylate derivative of a deprotected glucose can be carried out in aqueous media. Furthermore, the resulting glucose-chelator conjugates can be radiolabeled with either Tc(V) or Re(V) in high radiochemical yields (>95%), to furnish separable mixtures of - and -[M(O)] (M = Tc, Re). Single photon emission computed tomography (SPECT) imaging and biodistribution in healthy mice show that each isomer possesses favorable pharmacokinetic properties, with rapid clearance from blood circulation via a renal pathway. Both -[Tc(O)] and -[Tc(O)] exhibit high stability in serum. This new class of functionalized diphosphine chelators has the potential to provide access to receptor-targeted dual diagnostic/therapeutic pairs of radiopharmaceutical agents, for molecular Tc SPECT imaging and Re systemic radiotherapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10731653 | PMC |
| http://dx.doi.org/10.1021/acs.inorgchem.2c04008 | DOI Listing |
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