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Noninvasive evaluation of PD-L1 expression in non-small cell lung cancer by immunoPET imaging using an acylating agent-modified antibody fragment.

التفاصيل البيبلوغرافية
العنوان: Noninvasive evaluation of PD-L1 expression in non-small cell lung cancer by immunoPET imaging using an acylating agent-modified antibody fragment.
المؤلفون: Cheng Y; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China., Shi D; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China., Ye R; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China., Fu W; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China., Ma P; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China., Si Z; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China., Xu Z; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China., Li L; Department of Hepatic Oncology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China., Lin Q; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China. lin.qingyu@zs-hospital.sh.cn.; Institute of Nuclear Medicine, Fudan University, Shanghai, 200032, China. lin.qingyu@zs-hospital.sh.cn.; Shanghai Institute of Medical Imaging, Shanghai, 200032, China. lin.qingyu@zs-hospital.sh.cn., Cheng D; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China. cheng.dengfeng@zs-hospital.sh.cn.; Institute of Nuclear Medicine, Fudan University, Shanghai, 200032, China. cheng.dengfeng@zs-hospital.sh.cn.; Shanghai Institute of Medical Imaging, Shanghai, 200032, China. cheng.dengfeng@zs-hospital.sh.cn.
المصدر: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2023 May; Vol. 50 (6), pp. 1585-1596. Date of Electronic Publication: 2023 Feb 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer-Verlag Berlin Country of Publication: Germany NLM ID: 101140988 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1619-7089 (Electronic) Linking ISSN: 16197070 NLM ISO Abbreviation: Eur J Nucl Med Mol Imaging Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Berlin : Springer-Verlag Berlin, 2002-
مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung* , Lung Neoplasms*/diagnostic imaging, Humans ; Immunoglobulin Fab Fragments/metabolism ; Tissue Distribution ; B7-H1 Antigen/metabolism ; Radiopharmaceuticals
مستخلص: Purpose: The aim of this study was to explore an effective 124 I labeling strategy and improve the signal-to-noise ratio when evaluating the expression of PD-L1 using an 124 I-iodinated durvalumab (durva) F(ab') 2 fragment.
Methods: The prepared durva F(ab') 2 fragments were incubated with N-succinimidyl-3-(4-hydroxyphenyl) propionate (SHPP); after purification, the HPP-durva F(ab') 2 was iodinated using Iodo-Gen method. After the radiochemical purity, stability, and specific activities were determined, the binding affinities of probes prepared using different labeling strategies were compared in vitro. The clinical application value of [ 124 I]I-HPP-durva-F(ab') 2 was confirmed by PET imaging. To more objectively evaluate the in vivo distribution and clearance of tracers, the pharmacokinetics and biodistribution assays were also performed.
Results: After being modified with SHPP, the average conjugation number of SHPP per durva-F(ab') 2 identified by LC-MS was about 8.92 ± 2.84. The prepared [ 124 I]I-HPP-durva F(ab') 2 was obtained with a satisfactory radiochemical purity of more than 98% and stability of more than 93% when incubated for 72 h. Compared with unmodified [ 124 I]I-durva F(ab') 2 , the specific activity of [ 124 I]I-HPP-durva-F(ab') 2 was improved (52.91 ± 5.55 MBq/mg and 15.91 ± 0.74 MBq/mg), while the affinity did not significantly change. The biodistribution experiments and PET imaging showed that the prepared [ 124 I]I-HPP-durva-F(ab') 2 exhibited an accelerated clearance and improved tumor-to-background ratio compared with [ 124 I]I-durva-F(ab') 2 . The specificity of [ 124 I]I-HPP-durva-F(ab') 2 to PD-L1 was well demonstrated both in vitro and in vivo.
Conclusions: A PD-L1 PET imaging probe [ 124 I]I-HPP-durva F(ab') 2 was successfully synthesized through the SHPP modification strategy. The prepared probe was able to accurately evaluate the PD-L1 expression level through high-contrast noninvasive imaging.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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معلومات مُعتمدة: 11875114 National Natural Science Foundation of China; 82172002 National Natural Science Foundation of China; 82272058 National Natural Science Foundation of China; 21XD1423500 Shanghai Municipal Science and Technology Committee of the Shanghai Outstanding Young Academic Leaders Plan; 2020ZSLC20 Zhongshan Hospital, Fudan university
فهرسة مساهمة: Keywords: F(ab')2 fragment; I-124; PD-L1; PET imaging; SHPP
المشرفين على المادة: 0 (Iodine-124)
0 (Immunoglobulin Fab Fragments)
0 (B7-H1 Antigen)
0 (Radiopharmaceuticals)
تواريخ الأحداث: Date Created: 20230209 Date Completed: 20230424 Latest Revision: 20230425
رمز التحديث: 20231215
DOI: 10.1007/s00259-023-06130-6
PMID: 36759371
قاعدة البيانات: MEDLINE
الوصف
تدمد:1619-7089
DOI:10.1007/s00259-023-06130-6