基于 Glypican-3 的Zr 和 Y 放射性核素靶向递呈平台用于肝细胞癌的诊断与治疗。
Glypican-3 targeted delivery of Zr and Y as a theranostic radionuclide platform for hepatocellular carcinoma.
机构信息
Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA.
Department of Radiology, University of Washington, Seattle, WA, USA.
出版信息
Sci Rep. 2021 Feb 12;11(1):3731. doi: 10.1038/s41598-021-82172-w.
Glypican-3 (GPC3) is a tumor associated antigen expressed by hepatocellular carcinoma (HCC) cells. This preclinical study evaluated the efficacy of a theranostic platform using a GPC3-targeting antibody αGPC3 conjugated to zirconium-89 (Zr) and yttrium-90 (Y) to identify, treat, and assess treatment response in a murine model of HCC. A murine orthotopic xenograft model of HCC was generated. Animals were injected with Zr-labeled αGPC3 and imaged with a small-animal positron emission/computerized tomography (PET/CT) imaging system (immuno-PET) before and 30 days after radioimmunotherapy (RIT) with Y-labeled αGPC3. Serum alpha fetoprotein (AFP), a marker of tumor burden, was measured. Gross tumor volume (GTV) and SUV by immuno-PET was measured using fixed intensity threshold and manual segmentation methods. Immuno-PET GTV measurements reliably quantified tumor burden prior to RIT, strongly correlating with serum AFP (R = 0.90). Serum AFP was significantly lower 30 days after RIT in Y-αGPC3 treated animals compared to those untreated (p = 0.01) or treated with non-radiolabeled αGPC3 (p = 0.02). Immuno-PET GTV measurements strongly correlated with tumor burden after RIT (R = 0.87), and GTV of animals treated with Y-αGPC3 was lower than in animals who did not receive treatment or were treated with non-radiolabeled αGPC3, although this only trended toward statistical significance. A theranostic platform utilizing GPC3 targeted Zr and Y effectively imaged, treated, and assessed response after radioimmunotherapy in a GPC3-expressing HCC xenograft model.
磷脂酰聚糖蛋白 3（GPC3）是肝细胞癌（HCC）细胞表达的肿瘤相关抗原。本临床前研究评估了一种治疗平台的疗效，该平台使用 GPC3 靶向抗体 αGPC3 与锆-89（Zr）和钇-90（Y）结合，以在 HCC 的小鼠模型中识别、治疗和评估治疗反应。生成了 HCC 的小鼠原位异种移植模型。在放射性免疫治疗（RIT）前和 RIT 后 30 天，用 Zr 标记的 αGPC3 对动物进行注射，并使用小动物正电子发射/计算机断层扫描（PET/CT）成像系统（免疫 PET）进行成像。测量血清甲胎蛋白（AFP），这是肿瘤负担的标志物。使用固定强度阈值和手动分割方法测量免疫 PET 的 GTV 和 SUV。免疫 PET GTV 测量在 RIT 前可靠地量化了肿瘤负担，与血清 AFP 强烈相关（R = 0.90）。与未接受治疗（p = 0.01）或接受非放射性标记的 αGPC3 治疗（p = 0.02）的动物相比，Y-αGPC3 治疗的动物的血清 AFP 在 RIT 后 30 天显着降低。免疫 PET GTV 测量与 RIT 后的肿瘤负担强烈相关（R = 0.87），并且接受 Y-αGPC3 治疗的动物的 GTV 低于未接受治疗或接受非放射性标记的 αGPC3 治疗的动物，尽管这仅具有统计学意义的趋势。一种利用 GPC3 靶向 Zr 和 Y 的治疗平台在 GPC3 表达 HCC 异种移植模型中有效成像、治疗和评估 RIT 后的反应。
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