Synthesis of tricarbonyl rhenium and technetium complexes of a 5′-carboxamide 5-ethyl-2′-deoxyuridine for selective inhibition of herpes simplex virus thymidine kinase 1

Herpes simplex virus thymidine kinase type 1 (HSV1-TK) is frequently used as reporter protein in gene therapy. Our aim is to produce single photon emitting reporter probe based on technetium-99m. The synthesis of organometallic technetium and rhenium complexes of a 5′-carboxamide 5-ethyl-2′-deoxyuridine derivative able to selectively inhibit HSV1-TK is presented. The 5-ethyl-2′-deoxyuridine functionalized with a suitable tridentate chelating system at position 5′ was synthesized from commercial 2′-deoxyuridine in seven steps. The 5-ethyl-2′-deoxyuridine derivative was labeled with the fac-M(CO)3-core (M = Tc, Re). The resulting rhenium complex was found to be a selective competitive inhibitor of HSV1-TK (Ki = 4.56 μM). Inhibition of the human cytosolic thymidine kinase (hTK1) previously reported with organometallic rhenium and technetium complexes of 5′-carboxamide thymidine derivative was not observed. The uptake of the technetium-99m complex in transfected cells expressing HSV1-TK has been evaluated to assess its possible use as reporter.