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新型镓和铟标记的亲和体分子Z用于正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）可视化恶性肿瘤中胰岛素样生长因子-1受体（IGF-1R）表达的临床前评估

Preclinical Evaluation of a New Format of Ga- and In-Labeled Affibody Molecule Z for the Visualization of IGF-1R Expression in Malignant Tumors Using PET and SPECT.

作者信息

Liu Yongsheng, Yu Shengze, Xu Tianqi, Bodenko Vitalina, Orlova Anna, Oroujeni Maryam, Rinne Sara S, Tolmachev Vladimir, Vorobyeva Anzhelika, Gräslund Torbjörn

机构信息

Department of Immunology, Genetics and Pathology, Uppsala University, 75237 Uppsala, Sweden.

Department of Protein Science, KTH Royal Institute of Technology, 10044 Stockholm, Sweden.

出版信息

Pharmaceutics. 2022 Jul 15;14(7):1475. doi: 10.3390/pharmaceutics14071475.

DOI:10.3390/pharmaceutics14071475
PMID:35890370
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9320461/
Abstract

The Insulin-like growth factor-1 receptor (IGF-1R) is a molecular target for several monoclonal antibodies undergoing clinical evaluation as anticancer therapeutics. The non-invasive detection of IGF-1R expression in tumors might enable stratification of patients for specific treatment and improve the outcome of both clinical trials and routine treatment. The affibody molecule Z binds specifically to IGF-1R with subnanomolar affinity. The goal of this study was to evaluate the Ga and In-labeled affibody construct NODAGA-(HE)-Z for the imaging of IGF-1R expression, using PET and SPECT. The labeling was efficient and provided stable coupling of both radionuclides. The two imaging probes, [Ga]Ga-NODAGA-(HE)-Z and [In]In-NODAGA-(HE)-Z, demonstrated specific binding to IGF-1R-expressing human cancer cell lines in vitro and to IGF-1R-expressing xenografts in mice. Preclinical PET and SPECT/CT imaging demonstrated visualization of IGF-1R-expressing xenografts already one hour after injection. The tumor-to-blood ratios at 3 h after injection were 7.8 ± 0.2 and 8.0 ± 0.6 for [Ga]Ga-NODAGA-(HE)-Z and [In]In-NODAGA-(HE)-Z, respectively. In conclusion, a molecular design of the Z affibody molecule, including placement of a (HE)-tag on the N-terminus and site-specific coupling of a NODAGA chelator on the C-terminus, provides a tracer with improved imaging properties for visualization of IGF-1R in malignant tumors, using PET and SPECT.

摘要

胰岛素样生长因子-1受体（IGF-1R）是几种正在进行临床评估作为抗癌治疗药物的单克隆抗体的分子靶点。肿瘤中IGF-1R表达的非侵入性检测可能有助于对患者进行特定治疗分层，并改善临床试验和常规治疗的结果。亲和体分子Z以亚纳摩尔亲和力特异性结合IGF-1R。本研究的目的是使用正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）评估镓（Ga）和铟（In）标记的亲和体构建体NODAGA-(HE)-Z对IGF-1R表达的成像。标记效率高，两种放射性核素均能稳定偶联。两种成像探针，[Ga]Ga-NODAGA-(HE)-Z和[In]In-NODAGA-(HE)-Z，在体外对表达IGF-1R的人癌细胞系以及在小鼠体内对表达IGF-1R的异种移植瘤均表现出特异性结合。临床前PET和SPECT/CT成像显示，注射后仅1小时即可观察到表达IGF-1R的异种移植瘤。[Ga]Ga-NODAGA-(HE)-Z和[In]In-NODAGA-(HE)-Z在注射后3小时的肿瘤与血液比值分别为7.8±0.2和8.0±0.6。总之，Z亲和体分子的分子设计，包括在N端放置一个（HE）标签以及在C端对NODAGA螯合剂进行位点特异性偶联，提供了一种具有改进成像特性的示踪剂，用于使用PET和SPECT在恶性肿瘤中可视化IGF-1R。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/7685d64eeabe/pharmaceutics-14-01475-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/32b6f1922288/pharmaceutics-14-01475-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/4d679126a973/pharmaceutics-14-01475-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/869e0a21e9fb/pharmaceutics-14-01475-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/c8941a1c2837/pharmaceutics-14-01475-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/ac85f9ee5173/pharmaceutics-14-01475-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/1be1c1798d4b/pharmaceutics-14-01475-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/7685d64eeabe/pharmaceutics-14-01475-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/32b6f1922288/pharmaceutics-14-01475-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/4d679126a973/pharmaceutics-14-01475-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/869e0a21e9fb/pharmaceutics-14-01475-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/c8941a1c2837/pharmaceutics-14-01475-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/ac85f9ee5173/pharmaceutics-14-01475-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/1be1c1798d4b/pharmaceutics-14-01475-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2af/9320461/7685d64eeabe/pharmaceutics-14-01475-g007.jpg

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