Human Epidermal Growth Factor Receptor 2-Targeting [68Ga]Ga-ABY-025 PET/CT Predicts Early Metabolic Response in Metastatic Breast Cancer.

IF 9.1 1区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Journal of Nuclear Medicine Pub Date : 2023-09-01 DOI:10.2967/jnumed.122.265364
Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y Frejd, Johan Hartman, Victor Iyer, Joachim Feldwisch, Mark Lubberink, Caroline Rönnlund, Vladimir Tolmachev, Irina Velikyan, Jens Sörensen
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引用次数: 2

Abstract

Imaging using the human epidermal growth factor receptor 2 (HER2)-binding tracer 68Ga-labeled ZHER2:2891-Cys-MMA-DOTA ([68Ga]Ga-ABY-025) was shown to reflect HER2 status determined by immunohistochemistry and in situ hybridization in metastatic breast cancer (MBC). This single-center open-label phase II study investigated how [68Ga]Ga-ABY-025 uptake corresponds to biopsy results and early treatment response in both primary breast cancer (PBC) planned for neoadjuvant chemotherapy and MBC. Methods: Forty patients with known positive HER2 status were included: 19 with PBC and 21 with MBC (median, 3 previous treatments). [68Ga]Ga-ABY-025 PET/CT, [18F]F-FDG PET/CT, and core-needle biopsies from targeted lesions were performed at baseline. [18F]F-FDG PET/CT was repeated after 2 cycles of therapy to calculate the directional change in tumor lesion glycolysis (Δ-TLG). The largest lesions (up to 5) were evaluated in all 3 scans per patient. SUVs from [68Ga]Ga-ABY-025 PET/CT were compared with the biopsied HER2 status and Δ-TLG by receiver operating characteristic analyses. Results: Trial biopsies were HER2-positive in 31 patients, HER2-negative in 6 patients, and borderline HER2-positive in 3 patients. The [68Ga]Ga-ABY-025 PET/CT cutoff SUVmax of 6.0 predicted a Δ-TLG lower than -25% with 86% sensitivity and 67% specificity in soft-tissue lesions (area under the curve, 0.74 [95% CI, 0.67-0.82]; P = 0.01). Compared with the HER2 status, this cutoff resulted in clinically relevant discordant findings in 12 of 40 patients. Metabolic response (Δ-TLG) was more pronounced in PBC (-71% [95% CI, -58% to -83%]; P < 0.0001) than in MBC (-27% [95% CI, -16% to -38%]; P < 0.0001), but [68Ga]Ga-ABY-025 SUVmax was similar in both with a mean SUVmax of 9.8 (95% CI, 6.3-13.3) and 13.9 (95% CI, 10.5-17.2), respectively (P = 0.10). In multivariate analysis, global Δ-TLG was positively associated with the number of previous treatments (P = 0.0004) and negatively associated with [68Ga]Ga-ABY-025 PET/CT SUVmax (P = 0.018) but not with HER2 status (P = 0.09). Conclusion: [68Ga]Ga-ABY-025 PET/CT predicted early metabolic response to HER2-targeted therapy in HER2-positive breast cancer. Metabolic response was attenuated in recurrent disease. [68Ga]Ga-ABY-025 PET/CT appears to provide an estimate of the HER2 expression required to induce tumor metabolic remission by targeted therapies and might be useful as an adjunct diagnostic tool.

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人表皮生长因子受体2靶向[68Ga]Ga-ABY-025 PET/CT预测转移性乳腺癌早期代谢反应
使用人表皮生长因子受体2 (HER2)结合示踪剂68Ga标记的HER2:2891- cys - mma - dota ([68Ga]Ga-ABY-025)的成像显示,通过免疫组织化学和原位杂交检测可以反映转移性乳腺癌(MBC)中HER2的状态。这项单中心开放标签II期研究调查了[68Ga]Ga-ABY-025摄取如何与计划进行新辅助化疗和MBC的原发性乳腺癌(PBC)活检结果和早期治疗反应相对应。方法:40例已知HER2阳性患者:19例PBC, 21例MBC(中位数,既往3次治疗)。[68Ga]Ga-ABY-025 PET/CT, [18F]F-FDG PET/CT,并在基线时对目标病变进行核心针活检。[18F]治疗2个周期后重复F-FDG PET/CT,计算肿瘤病灶糖酵解方向变化(Δ-TLG)。每个患者在所有3次扫描中评估最大的病变(最多5个)。通过受试者工作特征分析,比较[68Ga] ga - abi -025 PET/CT suv活检后HER2状态和Δ-TLG。结果:31例her2阳性,6例her2阴性,3例her2阳性。[68Ga]Ga-ABY-025 PET/CT临界值SUVmax为6.0,预测软组织病变的敏感性为86%,特异性为67%(曲线下面积0.74 [95% CI, 0.67-0.82];P = 0.01)。与HER2状态相比,40例患者中有12例出现临床相关的不一致结果。代谢反应(Δ-TLG)在PBC中更为明显(-71% [95% CI, -58%至-83%];P < 0.0001)比MBC (-27% [95% CI, -16%至-38%];P < 0.0001),但[68Ga]Ga-ABY-025 SUVmax在两者中相似,平均SUVmax分别为9.8 (95% CI, 6.3-13.3)和13.9 (95% CI, 10.5-17.2) (P = 0.10)。在多变量分析中,全球Δ-TLG与既往治疗次数呈正相关(P = 0.0004),与[68Ga]Ga-ABY-025 PET/CT SUVmax负相关(P = 0.018),但与HER2状态无关(P = 0.09)。结论:[68Ga]Ga-ABY-025 PET/CT预测her2阳性乳腺癌对her2靶向治疗的早期代谢反应。复发性疾病的代谢反应减弱。[68Ga]Ga-ABY-025 PET/CT似乎提供了靶向治疗诱导肿瘤代谢缓解所需的HER2表达的估计,可能是一种有用的辅助诊断工具。
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来源期刊
Journal of Nuclear Medicine
Journal of Nuclear Medicine 医学-核医学
CiteScore
13.00
自引率
8.60%
发文量
340
审稿时长
1 months
期刊介绍: The Journal of Nuclear Medicine (JNM), self-published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), provides readers worldwide with clinical and basic science investigations, continuing education articles, reviews, employment opportunities, and updates on practice and research. In the 2022 Journal Citation Reports (released in June 2023), JNM ranked sixth in impact among 203 medical journals worldwide in the radiology, nuclear medicine, and medical imaging category.
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