Abstract：
Nectin cell adhesion molecule 4 (nectin-4) is a transmembrane protein overexpressed on a variety of cancers and plays an important role in oncogenic and metastatic processes. The nectin-4-targeted antibody-drug conjugate enfortumab vedotin has been approved for treating locally advanced or metastatic urothelial cancer, but the efficacy in other types of cancer remains to be explored. The aim of this study was to evaluate the feasibility of nectin-4-targeted PET imaging with 68Ga-N188 as a noninvasive method to quantify membranous nectin-4 expression in multiple tumor types-an approach that may provide insight for patient stratification and treatment selection. Methods: Sixty-two patients with 16 types of cancer underwent head-to-head 68Ga-N188 and 18F-FDG PET/CT imaging for initial staging or detection of recurrence and metastases. Correlation between lesion SUVmax and nectin-4 expression determined by immunohistochemistry staining was analyzed in 36 of 62 patients. Results: The SUVmax of 68Ga-N188 had a positive correlation with membranous nectin-4 expression in the various tumor types tested (r = 0.458; P = 0.005), whereas no association was observed between the SUVmax and cytoplasmic nectin-4 expression. The detection rates for patient-based analysis of 68Ga-N188 and 18F-FDG PET/CT examinations were comparable (95.00% [57/60] vs. 93.33% [56/60]). In patients with pancreatic cancer, 68Ga-N188 exhibited a potential advantage for detecting residual or locally recurrent tumors; this advantage may assist in clinical decision-making. Conclusion: The correlation between nectin-4-targeted 68Ga-N188 PET imaging and membranous nectin-4 expression indicates the potential of 68Ga-N188 as an effective tool for selecting patients who may benefit from enfortumab vedotin treatment. The PET imaging results provided evidence to explore nectin-4-targeted therapy in a variety of tumors. 68Ga-N188 may improve the restaging of pancreatic cancer but requires further evaluation in a powered, prospective setting.
摘要：
Nectin细胞粘附分子4（nectin-4）是一种在多种癌症中过度表达的跨膜蛋白，在致癌和转移过程中起重要作用。nectin-4靶向抗体-药物偶联物enfortumabvedotin已被批准用于治疗局部晚期或转移性尿路上皮癌。但对其他类型癌症的疗效仍有待探索。这项研究的目的是评估使用68Ga-N188进行nectin-4靶向PET成像作为一种非侵入性方法来量化多种肿瘤类型中膜性nectin-4表达的可行性-这种方法可以为患者分层提供见解和治疗选择。方法：对62例16种癌症患者进行头对头68Ga-N188和18F-FDGPET/CT成像，以进行初始分期或检测复发和转移。分析了62例患者中36例通过免疫组织化学染色确定的病灶SUVmax与nectin-4表达之间的相关性。结果：68Ga-N188的SUVmax与膜nectin-4的表达呈正相关（r=0.458；P=0.005），而SUVmax与胞质nectin-4表达之间未观察到相关性。68Ga-N188和18F-FDGPET/CT检查的基于患者分析的检出率相当(95.00%[57/60]与93.33%[56/60]）。在胰腺癌患者中，68Ga-N188显示出检测残留或局部复发肿瘤的潜在优势;该优势可能有助于临床决策。结论：nectin-4靶向68Ga-N188PET成像与膜性nectin-4表达之间的相关性表明68Ga-N188可能是选择可能从enfortumabvedotin治疗中受益的患者的有效工具。PET成像结果为探索各种肿瘤的nectin-4靶向治疗提供了依据。68Ga-N188可以改善胰腺癌的再分期，但需要进一步评估，前瞻性设置。
