Impact of 68Ga-NOTA-MAL-MZHER2 PET imaging in advanced gastric cancer patients and therapeutic response monitoring.

Abstract

PURPOSE:

Clinical PET imaging of human epidermal growth factor receptor 2 (HER2) can noninvasively detect HER2 overexpression in lesions. A novel 68Ga-NOTA-MAL-MZHER2 (68Ga-HER2) affibody 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) were 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 patients) were scanned at 1, 2, and 3 h post-injection to determine the best imaging timepoint, and the remaining patients were scanned at the 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 lesion maxima were analyzed for each organ.

RESULTS:

(1) The 68Ga-HER2 affibody was safe and effective, and optimal image contrast was observed 2 h post-injection; the average 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 a SUVmax cutoff value 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 in the primary lesion, was relatively lower (SUVmax 7.3 ± 3.7). (4) Patients receiving therapy had a non-significantly lower lesion SUVmax than patients not receiving 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 underwent baseline PET/CT followed by targeted anti-HER2 therapy. Patients with lesions showing high avidity to the 68Ga-HER2 affibody showed longer progression-free survival (PFS) than those with lesions showing low avidity (4-9 m vs 2-3 m).

CONCLUSION:

68Ga-HER2 affibody PET/CT is a feasible method to noninvasively detect the HER2 status in AGC patients and enable early detection with a low dose. Ongoing anti-HER2 therapy did not influence 68Ga-HER2 affibody imaging, which allowed repeated evaluations to monitor the 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.

• Authors: Nina Zhou, Chang Liu, Xiaoyi Guo, Yuping Xu, Jifang Gong, Changsong Qi, Xiaotian Zhang, Min Yang, Hua Zhu, Lin Shen, Zhi Yang
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 48 Issue 1 Pg. 161-175 (01 2021) ISSN: 1619-7089 [Electronic] Germany
• PMID: 32564171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gallium Radioisotopes
• Heterocyclic Compounds, 1-Ring
• 1,4,7-triazacyclononane-N,N',N''-triacetic acid

Topics

• Gallium Radioisotopes
• Heterocyclic Compounds, 1-Ring
• Humans
• Positron Emission Tomography Computed Tomography
• Positron-Emission Tomography
• Stomach Neoplasms (diagnostic imaging, therapy)