Sharma Sai Kiran, Sevak Kuntal K, Monette Sebastien, Carlin Sean D, Knight James C, Wuest Frank R, Sala Evis, Zeglis Brian M, Lewis Jason S
Department of Radiology and the Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
Department of Radiology and the Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
J Nucl Med. 2016 May;57(5):771-6. doi: 10.2967/jnumed.115.167072. Epub 2016 Feb 2.
The elevation of cancer antigen 125 (CA125) levels in the serum of asymptomatic patients precedes the radiologic detection of high-grade serous ovarian cancer by at least 2 mo and the final clinical diagnosis by 5 mo. PET imaging of CA125 expression by ovarian cancer cells may enhance the evaluation of the extent of disease and provide a roadmap to surgery as well as detect recurrence and metastases.
(89)Zr-labeled mAb-B43.13 was synthesized to target CA125 and evaluated via PET imaging and biodistribution studies in mice bearing OVCAR3 human ovarian adenocarcinoma xenografts. Ex vivo analysis of tumors and lymph nodes was performed via autoradiography, histopathology, and immunohistochemistry.
PET imaging using (89)Zr-DFO-mAb-B43.13 (DFO is desferrioxamine) clearly delineated CA125-positive OVCAR3 xenografts as early as 24 h after the administration of the radioimmunoconjugate. Biodistribution studies revealed accretion of (89)Zr-DFO-mAb-B43.13 in the OVCAR3 tumors, ultimately reaching 22.3 ± 6.3 percentage injected dose per gram (%ID/g) at 72 h after injection. Most interestingly, activity concentrations greater than 50 %ID/g were observed in the ipsilateral lymph nodes of the xenograft-bearing mice. Histopathologic analysis of the immuno-PET-positive lymph nodes revealed the presence of grossly metastasized ovarian cancer cells within the lymphoid tissues. In control experiments, only low-level, non-specific uptake of (89)Zr-labeled isotype IgG was observed in OVCAR3 tumors; similarly, low-activity concentrations of (89)Zr-DFO-mAb-B43.13 accumulated in CA125-negative SKOV3 tumors.
Immuno-PET with (89)Zr-labeled mAb-B43.13 is a potential strategy for the noninvasive delineation of extent of disease and may add value in treatment planning and treatment monitoring of high-grade serous ovarian cancer.
无症状患者血清中癌抗原125（CA125）水平升高至少比高级别浆液性卵巢癌的影像学检测提前2个月，比最终临床诊断提前5个月。通过正电子发射断层显像（PET）对卵巢癌细胞中CA125表达进行成像，可能会增强对疾病范围的评估，并为手术提供路线图，同时检测复发和转移情况。
合成了以CA125为靶点的（89）Zr标记的单克隆抗体B43.13，并通过PET成像和生物分布研究在携带人卵巢腺癌异种移植瘤OVCAR3的小鼠中进行评估。通过放射自显影、组织病理学和免疫组织化学对肿瘤和淋巴结进行体外分析。
使用（89）Zr-DFO-单克隆抗体B43.13（DFO是去铁胺）进行PET成像，在注射放射免疫缀合物后24小时就清晰地勾勒出CA125阳性的OVCAR3异种移植瘤。生物分布研究显示（89）Zr-DFO-单克隆抗体B43.13在OVCAR3肿瘤中聚集，注射后72小时最终达到每克22.3±6.3%注射剂量（%ID/g）。最有趣的是，在携带异种移植瘤的小鼠同侧淋巴结中观察到活性浓度大于50%ID/g。对免疫PET阳性淋巴结的组织病理学分析显示，淋巴组织内存在明显转移的卵巢癌细胞。在对照实验中，在OVCAR3肿瘤中仅观察到（89）Zr标记的同型IgG的低水平非特异性摄取；同样，（89）Zr-DFO-单克隆抗体B43.13在CA125阴性的SKOV3肿瘤中积累的活性浓度较低。
用（89）Zr标记的单克隆抗体B43.13进行免疫PET是一种无创描绘疾病范围的潜在策略，可能会在高级别浆液性卵巢癌的治疗规划和治疗监测中增加价值。
