Synthesis of 99mTc(CO)3-deoxyuridine derivatives as potential HSV1-tk gene expression imaging agents

In this study, we synthesized Tc-99m(CO)(3)-2'-aminomethylpyridyl-2'-deoxyuridine (Tc-99m(CO)(3)-AMPDU) and Tc-99m(CO)(3)-aminoethylpyridyl-2'-deoxyuridine (Tc-99m(CO)(3)-AEPDU) as potential agents for imaging the expression of the non-invasive herpes simplex virus type-1 thymidine kinase. AMPDU and AEPDU were synthesized from uridine in five chemical steps and then labeled with [Tc-99m(CO)(3)(H2O)(3)](+) (370 MBq/0.5 mL) at 100 degrees C for 10 min. Under optimal conditions (0.5 and 1.0 mg for AMPDU and AEPDU and heating for 10 min), the labeling efficiency was 95.3 +/- 2.8% for AMPDU and 94.2 +/- 5.1% for AEPDU. To validate the chemical structure of Tc-99m(CO)(3)-labcled compounds, we also synthesized ReBr(CO)(3)-AMPDU and ReBr(CO)(3)-AEPDU by reacting [Et4N][ReBr3(CO)(3)] and AMPDU or AEPDU in methanol at 25 degrees C for 6h. Tc-99m(CO)(3)-AMPDU and Tc-99m(CO)(3)-AEPDU had the same retention time on HPLC analysis as ReBr(CO)(3)-AMPDU and ReBr(CO)(3)-AEPDU. (99)mTc(CO)(3)-AMPDU Lind Tc-99m(CO)(3)-AEPDU had high radiochemical stabilities of 98.1 +/- 1.5% and 98.0 +/- 1.7% for 6 h, respectively. (c) 2008 Elsevier Ltd. All rights reserved.