Theranostics with somatostatin receptor antagonists in SCLC: Correlation of 68Ga-SSO120 PET with immunohistochemistry and survival

IF 12.4 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Theranostics Pub Date : 2024-08-26 DOI:10.7150/thno.98819

Ilektra Antonia Mavroeidi, Anna Romanowicz, Tristan Haake, Johannes Wienker, Martin Metzenmacher, Kaid Darwiche, Filiz Oezkan, Servet Bölükbas, Martin Stuschke, Lale Umutlu, Marcel Opitz, Michael Nader, Rainer Hamacher, Jens Siveke, Jane Winantea, Wolfgang P. Fendler, Marcel Wiesweg, Wilfried E. E. Eberhardt, Ken Herrmann, Dirk Theegarten, Martin Schuler, Hubertus Hautzel, David Kersting

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引用次数: 0

Abstract

Rationale: Positron Emission Tomography (PET) using the somatostatin receptor 2 (SSTR2)-antagonist satoreotide trizoxetan (⁶⁸Ga-SSO120) is a novel, promising imaging modality for small-cell lung cancer (SCLC), which holds potential for theranostic applications. This study aims to correlate uptake in PET imaging with SSTR2 expression in immunohistochemistry (IHC) and to assess the prognostic value of ⁶⁸Ga-SSO120 PET at initial staging of patients with SCLC./nMethods: We analyzed patients who underwent ⁶⁸Ga-SSO120 PET/CT during initial diagnostic workup of SCLC as part of institutional standard-of-care. SSTR2 expression in IHC was evaluated on a 4-level scale and correlated with normalized standardized uptake values and tumor-to-liver ratios (SUV_max and TLR_peak) in ⁶⁸Ga-SSO120 PET on a lesion level. Highest lesion SUV_max/TLR_peak per patient, SSTR2 score in IHC, M status according to TNM classification, and other parameters were analyzed for association with overall survival (OS) and time to treatment failure (TTF) by univariate, multivariate (cut-off values were identified on data for best separation), and stratified Cox regression./nResults: We included 54 patients (24 men/30 women, median age 65 years, 21 M0/33 M1 according to TNM classification). In 43 patients with available surplus tumor tissue samples, hottest lesion SUV_max/TLR_peak showed a significant correlation with the level of SSTR2-expression by tumor cells in IHC (Spearman's rho 0.86/0.81, both p < 0.001; ANOVA p < 0.001). High SSTR2 expression in IHC, ⁶⁸Ga-SSO120 SUV_max and TLR_peak of the hottest lesion per patient, whole-body TLR_mean, MTV, TLG, M status, and serum LDH showed a significant association with inferior TTF/OS in univariate analysis. In separate multivariate Cox regression (including sex, age, M stage, and LDH) higher hottest-lesion TLR_peak showed a significant association with shorter OS (HR = 0.26, 95%CI: 0.08-0.84, p = 0.02) and SSTR2 expression in IHC with significantly shorter TTF (HR = 0.24, 95%CI: 0.08-0.71, p = 0.001) and OS (HR = 0.22, 95%CI: 0.06-0.84, p = 0.03). In total, 12 patients (22.2%) showed low (< 1), 21 (38.9%) intermediate (≥ 1 but < 2), 14 (25.9%) high (≥ 2 but < 5), and 7 (13.0%) very high (≥ 5) whole-body mean TLR_mean./nConclusion: In patients with SCLC, SSTR2 expression assessed by ⁶⁸Ga-SSO120 PET and by IHC were closely correlated and associated with shorter survival. More than 75% of patients showed higher whole-body⁶⁸Ga-SSO120 tumor uptake than liver uptake and almost 40% high or very high uptake, possibly paving the way towards theranostic applications.

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使用体生长抑素受体拮抗剂对 SCLC 进行治疗：68Ga-SSO120 PET 与免疫组化和生存期的相关性

理论依据：使用体生长抑素受体2（SSTR2）拮抗剂沙度列汀三唑锡（68Ga-SSO120）的正电子发射断层扫描（PET）是一种新型、有前景的小细胞肺癌（SCLC）成像模式，具有治疗应用的潜力。本研究旨在将 PET 成像摄取与免疫组化（IHC）中 SSTR2 的表达相关联，并评估 68Ga-SSO120 PET 在 SCLC 患者初始分期中的预后价值：我们对在SCLC初步诊断过程中接受68Ga-SSO120 PET/CT检查的患者进行了分析，这是机构标准治疗的一部分。对IHC中SSTR2的表达进行了4级评估，并将其与68Ga-SSO120 PET的归一化标准化摄取值和肿瘤-肝脏比值（SUVmax和TLRpeak）在病灶水平上进行了关联。通过单变量、多变量（根据数据确定截断值以实现最佳分离）和分层 Cox 回归分析了每位患者的最高病灶 SUVmax/TLRpeak、IHC 中的 SSTR2 评分、TNM 分类中的 M 状态和其他参数与总生存期（OS）和治疗失败时间（TTF）的关系：我们共纳入了 54 名患者（24 名男性/30 名女性，中位年龄 65 岁，根据 TNM 分类，21 名 M0/33 名 M1）。在 43 例有多余肿瘤组织样本的患者中，最热病灶 SUVmax/TLRpeak 与肿瘤细胞在 IHC 中的 SSTR2 表达水平有显著相关性（Spearman's rho 0.86/0.81，均 p < 0.001；方差分析 p < 0.001）。在单变量分析中，IHC中SSTR2的高表达、68Ga-SSO120 SUVmax和每位患者最热病灶的TLR峰值、全身TLR平均值、MTV、TLG、M状态和血清LDH与TTF/OS低下有显著相关性。在单独的多变量 Cox 回归中（包括性别、年龄、M 分期和 LDH），最热病灶 TLRpeak 越高，OS 越短（HR = 0.26，95%CI：0.08-0.84，p = 0.02），IHC 中 SSTR2 表达越高，TTF 越短（HR = 0.24，95%CI：0.08-0.71，p = 0.001），OS 越短（HR = 0.22，95%CI：0.06-0.84，p = 0.03）。共有 12 例患者（22.2%）的全身平均 TLR 值为低（< 1），21 例（38.9%）为中等（≥ 1 但< 2），14 例（25.9%）为高（≥ 2 但< 5），7 例（13.0%）为极高（≥ 5）：在SCLC患者中，68Ga-SSO120 PET和IHC评估的SSTR2表达密切相关，并与较短的生存期相关。75%以上的患者全身68Ga-SSO120肿瘤摄取率高于肝脏摄取率，近40%的患者摄取率很高或非常高，这可能为治疗学应用铺平了道路。

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来源期刊

Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

25.40

自引率

1.60%

发文量

433

审稿时长

1 months

期刊介绍： Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.