Radiopharmaceutical applications of technetium 3-oxy-4-pyrones and 3-oxy-4-pyridinones and gallium 3-oxy-4-pyridinones
Creators: name: Webb, Gordon A.
Publisher: name: University of British Columbia
Year: 2010

description: Ammonium pertechnetate [NH₄][TⅽO₄] was reacted with the following ligands via the reduction route: 3-hydroxy-2-methyl-4-pyrone (maltol), 5-hydroxy-2-hydroxymethyl-4-pyrone (kojic acid), 3-hydroxy-2-methyl-4-pyridinone (Hmpp), 3-hydroxy-l,2-dimethyl-4-pyridinone (Hdpp), 3-hydroxy-2-methyl-l-hexyl-4-pyridinone (Hmhpp), 3-hydroxy-2-methyl-l-undecanato-4-pyridinone (Hmupp), and β-[N-(3-hydroxy-4-pyridinone)]-α-aminopropionic acid (l-mimosine). The products from the reduction route were characterized by mass spectrometry, infrared spectrometry, ultraviolet spectroscopy, and conductivity‧measurements. Initial results indicate the formation of mono-cationic tris-ligand complexes of tin and technetium ([TcL₃]⁺and [SnL₃]⁺). The formation of Tc (V) complexes via a substitution route was also investigated. [Bu₄N][TcOCl₄] was reacted with: 3-hydroxy-2-methyl-4-pyrone (maltol), 5-hydroxy-2-hydroxymethyl-4-pyrone (kojic acid), and β-[N-(3-hydroxy-4-pyridinone)]-α-aminopropionic acid (l-mimosine). The 3-hydroxy-4-pyridinone used in this study (except mimosine) were prepared by the conversion of an oxygen heterocycle, 3-hydroxy-2-methyl-4-pyrone, to the corresponding nitrogen heterocycle by reaction with a primary amine. These potentially bidentate ligands contain an α-hydroxyketone moiety and their conjugate bases form mono-cationic tris-ligand technetium complexes. Hmupp, a new compound, was fully characterized by mass spectrometry, infrared spectrometry, proton NMR, ultraviolet spectroscopy, and elemental analysis. Initial clearance studies were done in a rabbit with the products of the reactions of [⁹⁹(formula omitted)TcO₄]- with Hdpp and Mimosine. Analogous to the synthetic procedure above using [⁹⁹Tc0₄]-, two products are formed ([⁹⁹(formula omitted)TcL3]⁺ and [SnL₃]⁺). The [SnL₃]⁺ complex is not radioactive and is therefore not visualized by the imaging procedure. The observed distribution is therefore that of the [⁹⁹(formula omitted)TcL₃]⁺ complex. The results of the clearance study with [⁹⁹(formula omitted)Tc(dpp)₃]⁺ show a small amount of liver, heart, and gall bladder uptake; however, the majority of the activity is rapidly excreted via the kidneys and bladder. There is also some gut uptake observed, and this is cleared much more slowly. The clearance study conducted with [⁹⁹(formula omitted)Tc(mimo)₃]⁺ shows results similar to those conducted with [⁹⁹(formula omitted)Tc(dpp)₃]⁺; however, less gut uptake and faster bladder clearance are observed with the mimosine complex. In addition to the technetium radiopharmaceutical work, some gallium-67 work was also done. This was done in collaboration with William Nelson and Don Lyster to complete an ongoing study of the in vitro and in vivo coordination chemistry of gallium 3-oxy-4-pyridinones as a model for the biodistribution of aluminum. ⁶⁷Ga-biodistribution studies were conducted with the following 3-hydroxy-4-pyridinone ligands: 3-hydroxy-2-methyl-4-pyridinone (Hrnpp), 3-hydroxy-l,2-dimethyl-4-pyridinone (Hdpp), 3-hydroxy-2-methyl-l-hexyl-4-pyridinone (Hmhpp), and β-[N-(3-hydroxy-4-pyridinone)]-α-aminopropionic acid (l-mimosine). The results of the biodistribution show that under conditions of excess ligand ⁶⁷Ga is redirected from transferrin; however, the ⁶⁷Ga-ligand complexes do not localize in any organs.