Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Oncology. 2013;84(4):200-9. doi: 10.1159/000338961. Epub 2013 Jan 15.
Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies.
To radiolabel bevacizumab with (99m)Tc(CO)3(OH2)3 and evaluate it in vivo and in vitro for melanoma imaging properties.
Bevacizumab was radiolabeled with (99m)Tc(CO)3(OH2)3 ion in saline. The radiochemical stability of the labeled antibody was assessed. The biodistribution and scintigraphy imaging of the radiolabeled antibody were evaluated in normal C57BL/6J mice and in C57BL/6J mice bearing murine B16F1 melanoma tumors. Immunoreactivity of bevacizumab to murine tumors was determined from direct immunofluorescence and immunoblotting assays.
We demonstrate that (99m)Tc(CO)3-bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc(CO)3-bevacizumab was 2.64 and 2.51 %ID/g at 4 and 24 h postinjection. Scintigraphy image studies showed tumor selective uptake of (99m)Tc(CO)3-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples.
(99m)Tc(CO)3-bevacizumab could be used as an approach for tumor nuclear imaging in preclinical studies. This should be useful to provide insights into the angiogenic stimulus before and after chemotherapy, which might help improve current antitumor therapy.
血管内皮生长因子（VEGF）是几种肿瘤类型（包括黑色素瘤）中肿瘤诱导血管生成的经典因子之一。贝伐单抗是一种针对 VEGF 的单克隆抗体，可用作临床前研究中的成像工具。
用 (99m)Tc(CO)3(OH2)3 对贝伐单抗进行放射性标记，并评估其在黑色素瘤成像特性方面的体内和体外表现。
贝伐单抗在盐水中用 (99m)Tc(CO)3(OH2)3 离子进行放射性标记。评估标记抗体的放射化学稳定性。在正常 C57BL/6J 小鼠和携带 C57BL/6J 小鼠黑色素瘤 B16F1 肿瘤的小鼠中评估放射性标记抗体的生物分布和闪烁成像。通过直接免疫荧光和免疫印迹分析测定贝伐单抗对小鼠肿瘤的免疫反应性。
我们证明了 (99m)Tc(CO)3-贝伐单抗是稳定的。体内生物分布研究表明，（99m）Tc(CO)3-贝伐单抗在注射后 4 和 24 小时的肿瘤摄取率分别为 2.64% 和 2.51%ID/g。闪烁成像研究表明，（99m）Tc(CO)3-贝伐单抗在荷瘤小鼠中具有肿瘤选择性摄取。这一亲和力在 B16F10 肿瘤样本上进行的免疫测定中得到了证实。
(99m)Tc(CO)3-贝伐单抗可用于临床前研究中的肿瘤核成像方法。这对于在化疗前后提供对血管生成刺激的深入了解可能会有所帮助，从而有助于改善当前的抗肿瘤治疗。
