PT  - JOURNAL ARTICLE
AU  - Xiaoyi Guo
AU  - Nina Zhou
AU  - Chang Liu
AU  - Yuping Xu
AU  - Mi Yang
AU  - Hua Zhu
AU  - Lin Shen
AU  - Zhi Yang
TI  - <strong><sup>68</sup>Ga-NOTA-MAL-MZHER2 Affibody: A feasible PET tracer for the noninvasive detection of lesions overexpressing HER2 in advanced gastric cancer patients and its utility in monitoring therapeutic response</strong>
DP  - 2020 May 01
TA  - Journal of Nuclear Medicine
PG  - 442--442
VI  - 61
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/61/supplement_1/442.short
4100  - http://jnm.snmjournals.org/content/61/supplement_1/442.full
SO  - J Nucl Med2020 May 01; 61
AB  - 442Purpose: Clinical PET imaging of human epidermal growth factor receptor 2 (HER2) can noninvasively detect HER2 overexpression in lesions and guide therapy. A novel 68Ga-HER2 affibody (68Ga-NOTA-MAL-MZHER2) was developed for clinical PET/CT, and its safety, tissue dosimetry, ability to detect HER2-positive lesions, and utility for HER2-targeted therapy in patients with advanced gastric cancer (AGC) was evaluated. Methods: Thirty-four patients with AGC (23 with HER2-positive and 11 with HER2-negative primary lesions) were included and underwent PET/CT after an injection of approximately 3.7 MBq/kg body weight 68Ga-HER2 affibody. Thirteen patients (8 HER2-positive and 5 HER2-negative) were imaged at 1, 2, and 3 h postinjection to determine the best imaging timepoint, and the remaining patients were imaged at this optimized timepoint. All patients underwent standard 18F-FDG PET/CT within 7 d to identify viable lesions. The SUVmax of lesions larger than 1.0 cm were analyzed. Five lesions maximum were analyzed for each organ. Results: (1) The 68Ga-HER2 affibody was safe and effective, and optimal image contrast was observed 2 h postinjection; the total effective absorbed dose was 0.0215 mSv/MBq. (2) The HER2-positive group had significantly higher 68Ga-HER2 affibody uptake than the HER2-negative group (SUVmax 10.7 ± 12.5 vs 3.8 ± 1.7, p=0.005). The specificity and sensitivity were 100% and 55.4%, respectively, with an SUVmax cutoff of 6.6. The SUVmax of the lesions ranged from 1.6 to 73.0, suggesting heterogeneity in HER2 expression. (3) 68Ga-HER2 affibody uptake showed an organ-dependent difference in patients with HER2-positive expression. Bone metastases had the highest uptake (SUVmax 40.5 ± 24.9), followed by liver metastases (SUVmax 11.9 ± 3.9) and lymph node metastases (SUVmax 5.6 ± 3.7), while the uptake in other lesions, including the primary lesion, was relatively lower (SUVmax 7.3 ± 3.7). (4) Patients treated with therapy had a nonsignificantly lower lesion SUVmax than patients without therapy (SUVmax 8.8 ± 4.9 vs 11.8 ± 15.2) (p = 0.253). Additionally, the 68Ga-HER2 affibody detected positive lesions in 1/11 patients with HER2-negative primary gastric cancer, which was confirmed by second generation gene sequencing. (5). Moreover, ten patients had baseline PET/CT followed by targeted anti-HER2 therapy. Patients with 68Ga-HER2 affibody-avid lesions showed longer progression-free survival (PFS) than non-avid patients (4-9 m vs 2-3 m). Conclusion: 68Ga-HER2 affibody PET/CT is a feasible method to noninvasively detect HER2 status in AGC patients and enables early detection with a low dose.Ongoing anti-HER2 therapy did not influence 68Ga-HER2 affibody imaging, which allowed repeated evaluations to monitor HER2 status after anti-HER2 therapy.This method provides an in vivo understanding of AGC biology that will ultimately help oncologists improve individualized therapy plans. Key Words: 68Ga-HER2 Affibody, 68Ga-NOTA-MAL-MZHER2, PET/CT, Gastric Cancer, Epidermal Growth Factor Receptor 2 Figure 1. PET/CT images (A: MIP, B: Axial CT, C: Axial PET, D: Axial PET/CT fusion) of patients with HER2-negative primary cancer (HER2 1+). The images of primary gastric cancer (1), lung metastasis (2), and brain metastasis (3) all showed high 68Ga-HER2 affibody uptake, and heterogeneous uptake was observed in the primary lesions (C1,D1). Figure 2. 68Ga-affibody PET/CT of the same patient before (A1-C1) and after (A2-C2) therapy. The MIP image showed that the metastases decreased in number and size (A1, A2). The right image showed that the largest liver lesion became smaller but still had uptake (B1, B2), and the bone metastasis in the left ilium disappeared (C1, C2).