ImmunoPET imaging and radioimmunotherapy of prostate cancer with an anti-Trop2 antibody

前列腺癌 放射免疫疗法 体内分布 流式细胞术 医学 癌症研究 前列腺 体内 癌症 抗体 核医学 内科学 单克隆抗体 免疫学 生物 生物技术
作者
Dawei Jiang,Lei Kang,Emily B. Ehlerding,Dalong Ni,Bo Yu,Weijun Wei,Jonathan W. Engle,Weibo Cai
出处
期刊:The Journal of Nuclear Medicine [Society of Nuclear Medicine and Molecular Imaging]
卷期号:59: 538-538
摘要

538 Objectives: Prostate cancer is the most common cancer among men, and timely intervention may significantly facilitate treatment. The trophoblast cell surface antigen 2 (Trop2) is a transmembrane glycoprotein that regulates cell renewal and proliferation, and is found overexpressed in many cancers. Herein, we aim to evaluate the Trop2 expression level on different prostate cancer cell lines and apply radioimmunotherapy for the treatment of murine models of prostate cancer. Methods: The anti-Trop2 antibody (AF650, Research And Diagnostic Systems, Inc.) was conjugated with NOTA and DTPA for radiolabeling of Cu-64 (half-life 12.7 h) and Y-90 (half-life: 64.1 h), respectively. Radio-TLC was used to validate the radiolabeling and quantify the labeling efficiency. Relative Trop2 expression in LapC4, PC3, and 22RV1 prostate cancer cell lines was examined using flow cytometry. PET imaging and biodistribution studies in subcutaneous models of prostate cancer using 64Cu-NOTA-AF650 were performed to evaluate the tracer’s targeting capacity and specificity in vivo. Furthermore, 90Y-DTPA-AF650 was used for the treatment of the subcutaneous tumor model, with PBS and Y-90 labeled non-specific IgG as control groups. Tumor sizes and mouse body weight were examined every other day for two weeks. At the end time point, blood samples and tumor samples were collected and analyzed for toxicity evaluation. Results: Among the three prostate cancer cell lines, Trop2 expression was highest in LapC4 cells, while PC3 and 22RV1 displayed lower Trop2 expression. PET imaging revealed the tracer (64Cu-NOTA-AF650) uptake in LapC4 tumors to be about 12.2 ± 1.8 %ID/g, while values for PC3 and 22RV1 were 7.5 ± 1.9 %ID/g and 7.7 ± 0.6 %ID/g at 48 h post-injection, respectively. Treatment of LapC4 tumor-bearing mice with 90Y-DTPA-AF650 showed significant inhibition of tumor growth, compared with the treatment with PBS and non-specific IgG. During the study, mouse body weight did not decrease by more than 15% for all groups. Blood tests and tumor section staining suggested lower toxicity and better treatment effect of 90Y-DTPA-AF650 than 90Y-DTPA-IgG. Conclusion: This study showed the differentiated expression of Trop2 in 3 different prostate cancer cell lines, and 64Cu-NOTA-AF650 provided a specific tracer for imaging of prostate cancer with Trop2 overexpression. In addition, 90Y-DTPA-AF650 successfully curtailed tumor growth with lower off-target toxicity when compared with non-specific IgG. Overall, this targeted antibody holds great promise for PET imaging and immunoradiotherapy of prostate cancer.

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