68Ga-三肽替普素 PET/CT 的潜在疗效及对头颈鳞癌和胰腺导管腺癌患者αvβ6 整合素表达的免疫组化验证。

Potential Efficacy of 68 Ga-Trivehexin PET/CT and Immunohistochemical Validation of αvβ6 Integrin Expression in Patients With Head and Neck Squamous Cell Carcinoma and Pancreatic Ductal Adenocarcinoma.

机构信息

From the Departments of Nuclear Medicine.

Histopathology, Fortis Memorial Research Institute, Gurgaon, Haryana, India.

出版信息

Clin Nucl Med. 2024 Aug 1;49(8):733-740. doi: 10.1097/RLU.0000000000005278. Epub 2024 May 14.

DOI:10.1097/RLU.0000000000005278

PMID:38768077

Abstract

PURPOSE

αvβ6 integrin is exclusively expressed in epithelial cells and is upregulated in many carcinomas, such as pancreatic ductal adenocarcinomas (PDACs) and head and neck squamous cell carcinomas (H&NSCCs). Trivehexin is a recently synthesized trimerized αvβ6 integrin selective nonapeptide, which can be labeled with a positron emitter like 68 Ga. This is a pilot study to assess the potential role of 68 Ga-Trivehexin PET/CT in patients with H&NSCC and PDAC and their correlation with αvβ6 integrin expression by the tumor tissue on immunohistochemistry (IHC).

PATIENTS AND METHODS

Thirty-two patients with suspected H&NSCC (n = 20) or PDAC (n = 12) underwent whole-body 68 Ga-Trivehexin PET/CT and 18 F-FDG PET/CT scans on 2 separate days. All 32 patients underwent biopsy from the tumor site for histopathological diagnosis and IHC for αvβ6 integrin expression. The degree of αvβ6 integrin expression on IHC was scored using the immunoreactive score and modified 4-point immunoreactive score classification.

RESULTS

The 68 Ga-Trivehexin PET images demonstrated increased tracer uptake (mean SUV max 5.9 ± 3.3) in the primary and metastatic lesions with good lesion delineation in 8 out of the 9 cases of PDACs. However, FDG PET showed increased tracer uptake in 7 cases (6.2 ± 2.6). Among various cases of H&NSCC, increased uptakes of 68 Ga-Trivehexin (6.6 ± 4.5) and 18 F-FDG (12.7 ± 6.7) were seen in 17 out of the 18 patients. The 2 cases of inflammatory changes with suspected disease recurrence showed increased tracer uptake in 18 F-FDG PET (7.98 ± 3.1) and no significant uptake in 68 Ga-Trivehexin PET (2.2 ± 0.34).IHC showed higher expression of αvβ6 integrins in lesions with higher uptake of 68 Ga-Trivehexin. A higher sensitivity, specificity, and accuracy of 68 Ga-Trivehexin PET over 18 F-FDG PET was seen for detection of primary and metastatic lesions.

CONCLUSIONS

68 Ga-Trivehexin is a promising noninvasive molecular imaging agent for tumors expressing αvβ6 integrin, especially in cases where 18 F-FDG PET/CT scan may be suboptimal due to its low uptake, or due to its nonspecific uptake around tumor sites.

摘要

目的

αvβ6 整联蛋白仅在上皮细胞中表达，并在上皮样细胞来源的肿瘤中上调，例如胰腺导管腺癌（PDAC）和头颈部鳞状细胞癌（H&NSCC）。Trivehexin 是一种最近合成的三聚体 αvβ6 整联蛋白选择性九肽，可用正电子发射体如 68 Ga 进行标记。这是一项初步研究，旨在评估 68 Ga-Trivehexin PET/CT 在 H&NSCC 和 PDAC 患者中的潜在作用，并通过免疫组化（IHC）评估其与肿瘤组织中 αvβ6 整联蛋白表达的相关性。

患者和方法

32 例疑似 H&NSCC（n = 20）或 PDAC（n = 12）的患者在 2 天内分别接受全身 68 Ga-Trivehexin PET/CT 和 18 F-FDG PET/CT 扫描。所有 32 例患者均从肿瘤部位进行活检，用于组织病理学诊断和 IHC 检测 αvβ6 整联蛋白表达。使用免疫反应评分和改良的 4 分免疫反应评分分类对 IHC 上的 αvβ6 整联蛋白表达程度进行评分。

结果

68 Ga-Trivehexin PET 图像显示，在 9 例 PDAC 中有 8 例，原发和转移性病变的示踪剂摄取增加（平均 SUV max 5.9 ± 3.3），病变边界良好。然而，FDG PET 显示 7 例（6.2 ± 2.6）示踪剂摄取增加。在各种 H&NSCC 病例中，18 例中有 17 例（6.6 ± 4.5）和 18 F-FDG（12.7 ± 6.7）示踪剂摄取增加。2 例怀疑疾病复发的炎症变化病例在 18 F-FDG PET 中显示示踪剂摄取增加（7.98 ± 3.1），而在 68 Ga-Trivehexin PET 中无明显摄取（2.2 ± 0.34）。IHC 显示，68 Ga-Trivehexin 摄取较高的病变中 αvβ6 整联蛋白表达较高。与 18 F-FDG PET 相比，68 Ga-Trivehexin PET 对原发和转移性病变的检测具有更高的敏感性、特异性和准确性。