Radiosynthesis of New [90Y]-DOTA-Based Maleimide Reagents Suitable for the Prelabeling of Thiol-Bearing L-Oligonucleotides and Peptides


Radiosynthesis of New [90Y]-DOTA-Based Maleimide Reagents Suitable for the Prelabeling of Thiol-Bearing L-Oligonucleotides and Peptides

Schlesinger, J.; Fischer, C.; Közle, I.; Vonhoff, S.; Klussmann, S.; Bergmann, R.; Pietzsch, H.-J.; Steinbach, J.

We describe the radiosynthesis of two new [90Y]-DOTA-based maleimide reagents, suitable for the mild radiolabeling of L-RNAs and peptides modified with thiol-bearing linkers. The synthesis procedure of both maleimide-bearing 90Y complexes, [{(2S)-2-[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl}tetraacetato][90Y]yttrate(1-)([90Y]3) and [{(2S)-2-(4-{[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoyl]amino}benzyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetrayl]tetraacetato}[90Y]yttrate(1-)([90Y]4), was optimized in terms of an easy purification method via solid-phase extraction (SPE). Application as well as reactivity of both maleimide reagents were initially evaluated by the prelabeling of glutathione (GSH) and a thiol-modified 12mer L-RNA as model substances. In comparison to the N-aryl maleimide-bearing complex [90Y]3, N-alkyl maleimide-bearing complex [90Y]4 showed an increased hydrolytic stability at pH g 7. A slightly higher reactivity was found for [90Y]3 by prelabeling of 0.1 and 1 μg glutathione, respectively, in phosphate buffer (pH 7.2) at room temperature. In terms of very high radiochemical yields, the direct radiolabeling of DOTA-L-RNA conjugate with [90Y]YCl3 proved to be more suitable than the prelabeling of the thiol-modified 12mer L-RNA derivative with [90Y]4.

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Publ.-Id: 13107