Noninvasive PET imaging of tumor PD-L1 expression with 64Cu-labeled Durvalumab.

IF 2 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
American journal of nuclear medicine and molecular imaging Pub Date : 2024-02-20 eCollection Date: 2024-01-01
Sara Malih, Wilson Lin, Zhongmin Tang, Molly C DeLuca, Jonathan W Engle, Behrouz Alirezapour, Weibo Cai, Mohammad J Rasaee
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引用次数: 0

Abstract

Breast cancer (BrCa) ranks as the most prevalent malignant neoplasm affecting women worldwide. The expression of programmed death-ligand 1 (PD-L1) in BrCa has recently emerged as a biomarker for immunotherapy response, but traditional immunohistochemistry (IHC)-based methods are hindered by spatial and temporal heterogeneity. Noninvasive and quantitative PD-L1 imaging using appropriate radiotracers can serve to determine PD-L1 expression in tumors. This study aims to demonstrate the viability of PET imaging with 64Cu-labeled Durvalumab (abbreviated as Durva) to assess PD-L1 expression using a murine xenograft model of breast cancer. Durvalumab, a human IgG1 monoclonal antibody against PD-L1, was assessed for specificity in vitro in two cancer cell lines (MDA-MB-231 triple-negative breast cancer cell line and AsPC-1 pancreatic cancer cell line) with positive and negative PD-L1 expression by flow cytometry. Next, we performed the in vivo evaluation of 64Cu-NOTA-Durva in murine models of human breast cancer by PET imaging and ex vivo biodistribution. Additionally, mice bearing AsPC-1 tumors were employed as a negative control. Tumor uptake was quantified based on a 3D region-of-interest (ROI) analysis of the PET images and ex vivo biodistribution measurements, and the results were compared against conventional IHC testing. The radiotracer uptake was evident in MDA-MB-231 tumors and showed minimal nonspecific binding, corroborating IHC-derived results. The results of the biodistribution showed that the MDA-MB-231 tumor uptake of 64Cu-NOTA-Durva was much higher than 64Cu-NOTA-IgG (a nonspecific radiolabeled IgG). In Conclusion, 64Cu-labeled Durvalumab PET/CT imaging offers a promising, noninvasive approach to evaluate tumor PD-L1 expression.

用 64Cu 标记的 Durvalumab 对肿瘤 PD-L1 表达进行无创 PET 成像。
乳腺癌(BrCa)是全球女性发病率最高的恶性肿瘤。最近,程序性死亡配体 1(PD-L1)在乳腺癌中的表达已成为免疫疗法反应的生物标志物,但基于免疫组化(IHC)的传统方法受到空间和时间异质性的阻碍。使用适当的放射性同位素进行无创和定量的 PD-L1 成像可用于确定肿瘤中的 PD-L1 表达。本研究旨在证明使用 64Cu 标记的 Durvalumab(缩写为 Durva)进行 PET 成像的可行性,利用小鼠乳腺癌异种移植模型评估 PD-L1 的表达。Durvalumab是一种针对PD-L1的人类IgG1单克隆抗体,我们通过流式细胞术在体外对两种PD-L1表达阳性和阴性的癌细胞系(MDA-MB-231三阴性乳腺癌细胞系和AsPC-1胰腺癌细胞系)进行了特异性评估。接下来,我们在人类乳腺癌小鼠模型中通过 PET 成像和体内外生物分布对 64Cu-NOTA-Durva 进行了体内评估。此外,我们还将携带 AsPC-1 肿瘤的小鼠作为阴性对照。根据 PET 图像的三维感兴趣区(ROI)分析和体内外生物分布测量对肿瘤摄取进行了量化,并将结果与传统的 IHC 检测进行了比较。MDA-MB-231肿瘤对放射性示踪剂的摄取非常明显,非特异性结合极少,证实了IHC得出的结果。生物分布结果显示,MDA-MB-231 肿瘤对 64Cu-NOTA-Durva 的摄取远高于 64Cu-NOTA-IgG(一种非特异性放射性标记的 IgG)。总之,64Cu标记的Durvalumab PET/CT成像为评估肿瘤PD-L1的表达提供了一种前景广阔的无创方法。
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来源期刊
American journal of nuclear medicine and molecular imaging
American journal of nuclear medicine and molecular imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
自引率
4.00%
发文量
4
期刊介绍: The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.
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