■本研究旨在评估通过基因重组制备的亲和体分子探针99mTc-(HE)3ZHER2:V2的生物分布和生物活性,并研究其在SKOV3卵巢癌和MDA-MB-361乳腺癌异种移植物中靶向人表皮生长因子受体2(HER2)成像的潜力。
■Affibody分子是通过基因重组产生的。使用反相高效液相色谱法(RP-HPLC)测定99mTc标记的HER2亲和体的放射化学纯度。通过计算平衡解离常数来评估SKOV3卵巢癌细胞和MDA-MB-361乳腺癌细胞(HER2阳性)中的HER2亲和力。在携带SKOV3肿瘤的Balb/c小鼠中评估99mTc标记的亲和体分子探针的生物分布。使用SKOV3、MDA-MB-361和AT-3(HER2阴性)异种移植物在Balb/c小鼠中评估肿瘤靶向特异性。
■Affibody(HE)3ZHER2:V2,通过重组基因表达产生,成功标记了99mTc,通过RP-HPLC测定,放射化学纯度为(96.0±1.7)%(n=3)。这种分子探针表现出与HER2阳性SKOV3细胞的特异性结合,表现出强烈的放射性吸收。生物分布分析显示99mTc-(HE)3ZHER2:V2在HER2阳性肿瘤给药后快速积累,主要通过泌尿系统清除。在将99mTc-(HE)3ZHER2:V2静脉注射到HER2阳性SKOV3和MDA-MB-361裸鼠模型中1-3小时后进行的单光子发射计算机断层扫描成像证实了肿瘤对分子探针的靶向摄取。
■在这项研究中开发的分子探针99mTc-(HE)3ZHER2:V2有效地靶向HER2,以在体内对HER2阳性SKOV3和MDA-MB-361异种移植物进行成像。它表现出快速的血液清除,没有明显的毒性作用,提示其作为检测肿瘤细胞中HER2表达的有价值的标志物的潜力。
UNASSIGNED: This study aimed to assess the biodistribution and bioactivity of the
affibody molecular probe 99mTc-(HE)3ZHER2:V2, prepared by genetic recombination, and to investigate its potential for targeted human epidermal growth factor receptor 2 (HER2) imaging in SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts.
UNASSIGNED: Affibody molecules were generated through genetic recombination. The radiochemical purity of the 99mTc-labeled HER2
affibody was determined using reverse phase high performance liquid chromatography (RP-HPLC). Evaluation of HER2 affinity in SKOV3 ovarian cancer cells and MDA-MB-361 breast cancer cells (HER2-positive) was conducted by calculating equilibrium dissociation constants. Biodistribution of the 99mTc-labeled
affibody molecular probe was assessed in Balb/c mice bearing SKOV3 tumors. Tumor targeting specificity was evaluated in Balb/c mice using SKOV3, MDA-MB-361, and AT-3 (HER2-negative) xenografts.
UNASSIGNED: Affibody (HE)3ZHER2:V2, generated through recombinant gene expression, was successfully labeled with 99mTc, achieving a radiochemical purity of (96.0 ± 1.7)% (n = 3) as determined by RP-HPLC. This molecular probe exhibited specific binding to HER2-positive SKOV3 cells, demonstrating intense radioactive uptake. Biodistribution analysis showed rapid accumulation of 99mTc-(HE)3ZHER2:V2 in HER2-positive tumors post-administration, primarily clearing through the urinary system. Single-photon emission computed tomography imaging conducted 1-3 h after intravenous injection of 99mTc-(HE)3ZHER2:V2 into HER2-positive SKOV3 and MDA-MB-361 nude mouse models confirmed targeted uptake of the molecular probe by the tumors.
UNASSIGNED: The molecular probe 99mTc-(HE)3ZHER2:V2 developed in this study effectively targets HER2 for imaging HER2-positive SKOV3 and MDA-MB-361 xenografts in vivo. It exhibits rapid blood clearance without evident toxic effects, suggesting its potential as a valuable marker for detecting HER2 expression in tumor cells.