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Purpose <p>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 <sup>68</sup>Ga-labeled tracer based on the albumin-binding domain-derived affinity protein 6 (ADAPT6) was developed to evaluate HER2 expression in breast cancer.</p> Methods <p>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 <sup>68</sup>Ga to produce [<sup>68</sup>Ga]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 [<sup>68</sup>Ga]Ga-NODAGA-ADAPT6 PET imaging to assess HER2 expression in primary and metastatic lesions.</p> Results <p>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, [<sup>68</sup>Ga]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.</p> Conclusion <p>[<sup>68</sup>Ga]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.</p>

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Development and clinical evaluation of [68Ga]Ga-NODAGA-ADAPT6 as a novel HER2-targeted PET radiotracer for breast cancer imaging and treatment monitoring

  • 期刊论文

  • 发表日期：

    2025年4月21日

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  • Weijing Tao,
  • Jinglin Zhang,
  • Xin Meng,
  • Xuedong Han,
  • Qiuhu Wang,
  • Yixiang Lin,
  • Luyi Cheng,
  • Minmin Liu,
  • Dongzhu Da,
  • Huai Zhang,
  • Junfu Fan,
  • Lianmei Zhang,
  • Shuangyue Liu,
  • Shuo Li,
  • Feng Gao,
  • Yi Ren

摘要

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.