Abstract
We report the carrier-free radiochemical synthesis of a neutral, bio-active, titanium-45 complex, [45Ti]Ti-salan-dipic. In 2012, the Huhn group at Universität Konstanz reported the non-radioactive compound, Ti-salan-dipic, and demonstrated therapeutic efficacy in a xenograft cervical cancer mouse model as well as enhanced in-vitro cytotoxicity over several other titanium-based chemotherapeutics [1]. The mechanism of action for this class of therapeutics is under investigation and the determination of which will be aided by radiotracing and PET with 45Ti. 45Ti was prepared by proton irradiation of natSc foil followed by extraction onto a polystyrene-based diol-resin (RAPP polymers) after dissolution of the foil in 37% HCl. Synthesis proceeded on the column after quenching the residual acidity with pyridine. The ligands, salan and dipic, were added sequentially in pyridine, with the release of the final compound upon ligand exchange to dipic. [45Ti]Ti-salan-dipic was characterized by radio-TLC on silica in 1:1 ethylacetate:chloroform in comparison to the cold compound. This is a hydrolytically stable, cytotoxic, 45Ti compound. The solid-phase synthesis is robust, and provides opportunity for producing other 45Ti tracers. PET and radiotracer studies with [45Ti]Ti-salan-dipic and other Ti-based cytotoxic compounds will aid in mechanism determination, drug design, and eventually more effective treatment of cancer.
Info
Conference Abstract, 2014
UN SDG Classification
DK Main Research Area
Science/Technology
