RESUMO
We previously reported on the monobody E1, which specifically targets the tumor marker hEphA2. In this study, we labeled NOTA-conjugated E1 with 64Cu (64Cu-NOTA-E1) and evaluated biologic characteristics. The uptake of 64Cu-NOTA-E1 in PC3 cells (a human prostate cancer cell line) with high expression of hEphA2 increased in a time-dependent manner. In PC3 xenograft mice, 64Cu-NOTA-E1 injected via the tail vein allowed visualization of tumors on positron emission tomography after 1 h and the highest uptake measured at 24 h post-injection. By contrast, the radioactivity of other tissues either did not increase or decreased over 24 h. This indicates that 64Cu-NOTA-E1 has high tumor uptake and retention, with rapid clearance, and low background values in other tissues. Therefore, 64Cu-NOTA-E1 should be suitable as a novel PET imaging agent for hEphA2-expressing tumors.
Assuntos
Anticorpos/química , Efrina-A2/genética , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Animais , Radioisótopos de Cobre , Efrina-A2/química , Compostos Heterocíclicos com 1 Anel/química , Humanos , Masculino , Camundongos , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Células PC-3 , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Receptor EphA2RESUMO
In this study, we synthesized (99m)Tc(CO)(3)-2'-aminomethylpyridyl-2'-deoxyuridine ((99m)Tc(CO)(3)-AMPDU) and (99m)Tc(CO)(3)-aminoethylpyridyl-2'-deoxyuridine ((99m)Tc(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 [(99m)Tc(CO)(3)(H(2)O)(3)](+) (370MBq/0.5 mL) at 100 degrees C for 10 min. Under optimal conditions (0.5 and 1.0mg 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 (99m)Tc(CO)(3)-labeled compounds, we also synthesized ReBr(CO)(3)-AMPDU and ReBr(CO)(3)-AEPDU by reacting [Et(4)N][ReBr(3)(CO)(3)] and AMPDU or AEPDU in methanol at 25 degrees C for 6h. (99m)Tc(CO)(3)-AMPDU and (99m)Tc(CO)(3)-AEPDU had the same retention time on HPLC analysis as ReBr(CO)(3)-AMPDU and ReBr(CO)(3)-AEPDU. (99m)Tc(CO)(3)-AMPDU and (99m)Tc(CO)(3)-AEPDU had high radiochemical stabilities of 98.1+/-1.5% and 98.0+/-1.7% for 6h, respectively.
