Development and clinical evaluation of [68Ga]Ga-NODAGA-ADAPT6 as a novel HER2-targeted PET radiotracer for breast cancer imaging and treatment monitoring.
Purpose: Accurate assessment of human epidermal growth factor receptor type 2 (HER2) expression is crucial for diagnosis, treatment planning, and monitoring of breast cancer patients. A 68Ga-labeled tracer based on the albumin-binding domain-derived affinity protein 6 (ADAPT6) was developed to evalu...
| Published in: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 52; no. 11; pp. 4078 - 4092 |
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| Main Authors: | , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Published: |
Springer Nature
Sep2025
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=187672861&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 187672861 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Sep2025 vid: 52 iid: 11 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 187672861 184622359 10.1007/s00259-025-07286-z 187672861 ppf: 4078 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Development and clinical evaluation of [68Ga]Ga-NODAGA-ADAPT6 as a novel HER2-targeted PET radiotracer for breast cancer imaging and treatment monitoring. aug: au: Tao, Weijing Zhang, Jinglin Meng, Xin Han, Xuedong Wang, Qiuhu Lin, Yixiang Cheng, Luyi Liu, Minmin Da, Dongzhu Zhang, Huai Fan, Junfu Zhang, Lianmei Liu, Shuangyue Li, Shuo Gao, Feng Ren, Yi affil: https://ror.org/00xpfw690 Department of Nuclear Medicine, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, 223300, Huai'an, Jiangsu, China sug: ab: Purpose: Accurate assessment of human epidermal growth factor receptor type 2 (HER2) expression is crucial for diagnosis, treatment planning, and monitoring of breast cancer patients. A 68Ga-labeled tracer based on the albumin-binding domain-derived affinity protein 6 (ADAPT6) was developed to evaluate HER2 expression in breast cancer. Methods: The gene encoding ADAPT6 was modified with N-terminal (GHEHEHEDANS) and C-terminal (GSSC) extensions to enhance its functionality. The precursor was synthesized, purified, and characterized, followed by radiolabeling with 68Ga to produce [68Ga]Ga-NODAGA-ADAPT6. In vivo metabolism and biodistribution studies were performed in HCC1954 (HER2-positive) and MDA-MB-468 (HER2-negative) tumor-bearing mice. Additionally, with ethical approval and informed consent, 22 breast cancer patients underwent [68Ga]Ga-NODAGA-ADAPT6 PET imaging to assess HER2 expression in primary and metastatic lesions. Results: The tracer was prepared with a radiochemical purity exceeding 99% and demonstrated high stability in vivo. Micro-PET/CT imaging revealed significant accumulation of the radiotracer in HCC1954 tumors, which was markedly reduced after HER2 blockade with trastuzumab. In contrast, MDA-MB-468 tumors showed minimal uptake. In the clinical study, [68Ga]Ga-NODAGA-ADAPT6 PET images displayed varying levels of radiotracer uptake in primary and metastatic lesions, which correlated well with the HER2 expression status determined by pathological analysis. Conclusion: [68Ga]Ga-NODAGA-ADAPT6 exhibited excellent pharmacokinetic properties and high specificity for HER2-expressing lesions in PET imaging. These findings highlight its potential as a promising tool for distinguishing different levels of HER2 expression in breast cancer, aiding in personalized treatment strategies. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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