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

In this study, we synthesized 99mTc(CO)3-2′-aminomethylpyridyl-2′-deoxyuridine (99mTc(CO)3-AMPDU) and 99mTc(CO)3-aminoethylpyridyl-2′-deoxyuridine (99mTc(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 [99mTc(CO)3(H2O)3]+ (370 MBq/0.5 mL) at 100 °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 99mTc(CO)3-labeled 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 °C for 6 h. 99mTc(CO)3-AMPDU and 99mTc(CO)3-AEPDU had the same retention time on HPLC analysis as ReBr(CO)3-AMPDU and ReBr(CO)3-AEPDU. 99mTc(CO)3-AMPDU and 99mTc(CO)3-AEPDU had high radiochemical stabilities of 98.1±1.5% and 98.0±1.7% for 6 h, respectively.