Wächter Sabine, Di Fazio Pietro, Maurer Elisabeth, Manoharan Jerena, Keber Corinna, Pfestroff Andreas, Librizzi Damiano, Bartsch Detlef K, Luster Markus, Eilsberger Friederike
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Marburg, 35043 Marburg, Germany.
Department of Pathology, University Hospital Marburg, 35043 Marburg, Germany.
Cancers (Basel). 2021 Nov 14;13(22):5688. doi: 10.3390/cancers13225688.
Several studies have demonstrated an expression of the prostate-specific membrane antigen (PSMA) in the cancer-related neovasculature of thyroid malignancies. Due to the poor prognosis and limited therapeutic options for patients with anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma, the aim of our study was to investigate the theranostic approach of PSMA expression in these patients. The PSMA uptake on Gallium-68 (Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) and glucose uptake on F-18-Fluordeoxyglucose (F-FDG)-PET/CTs were analysed in two ATC and six PDTC patients. The PSMA expression in corresponding patients' tissue samples was detected by immunohistochemistry. In addition, various tissue sections from 22 ATC and six PDTC patients were examined concerning PSMA expression. Ga-PSMA-PET/CT showed heterogeneous PSMA expression among patients and lesions. Six of the eight analyzed patients (two ATC, four PDTC) showed increased glucose metabolism without increased PSMA uptake after PET/CT. In one patient (PDTC), F-FDG-PET/CT tracer uptake was positive and Ga-PSMA-PET/CT showed heterogeneous results. Another patient (PDTC) evidenced only PSMA-positive lesions and received two cycles of Lutetium-177 (Lu)-PSMA therapy, which kept his disease stable for seven months. There was a correlation between immunohistochemical PSMA expression and uptake on Ga-PMSA-PET/CT in three of the examined patients. Twenty-seven of the analyzed 39 ATC and 13 of the analyzed 22 PDTC tissue sections showed a strong PSMA expression. Considering the rarity of PDTC and ATC, which is the reason for the small patient population we studied, the findings of this study confirm the high diagnostic sensitivity and superiority of F-FDG-PET/CT in comparison to Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by F-FDG-PET/CT and to determine patients' eligibility for a radioligand therapy. Radiolabelled PSMA-ligands may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective. However, due to the small sample size of our collective, larger studies are needed to allow for a final evaluation on the significance of PSMA-targeted diagnostic and therapy for ATC and PDTC.
多项研究已证实前列腺特异性膜抗原（PSMA）在甲状腺恶性肿瘤的癌相关新生血管中表达。由于间变性（ATC）和低分化（PDTC）甲状腺癌患者预后较差且治疗选择有限，我们研究的目的是探讨PSMA表达在这些患者中的诊疗方法。分析了2例ATC患者和6例PDTC患者的68镓（Ga）-PSMA正电子发射断层扫描/计算机断层扫描（PET/CT）上的PSMA摄取情况以及18F-氟脱氧葡萄糖（F-FDG）-PET/CT上的葡萄糖摄取情况。通过免疫组织化学检测相应患者组织样本中的PSMA表达。此外，对22例ATC患者和6例PDTC患者的各种组织切片进行了PSMA表达检查。Ga-PSMA-PET/CT显示患者和病变之间PSMA表达存在异质性。8例分析患者中的6例（2例ATC，4例PDTC）在PET/CT后显示葡萄糖代谢增加而PSMA摄取未增加。在1例患者（PDTC）中，F-FDG-PET/CT示踪剂摄取为阳性，而Ga-PSMA-PET/CT显示结果异质性。另1例患者（PDTC）仅显示PSMA阳性病变，并接受了2个周期的177镥（Lu）-PSMA治疗，其疾病稳定了7个月。在所检查的3例患者中，免疫组织化学PSMA表达与Ga-PMSA-PET/CT上的摄取之间存在相关性。39例分析的ATC组织切片中有27例以及22例分析的PDTC组织切片中有13例显示PSMA强表达。考虑到PDTC和ATC的罕见性，这也是我们研究的患者群体较小的原因，本研究结果证实了F-FDG-PET/CT在ATC和PDTC诊断中与Ga-PSMA-PET/CT相比具有更高的诊断敏感性和优越性。然而，可以提出，对于少数选定的ATC和PDTC个体患者，Ga-PMSA-PET/CT可被视为成熟的F-FDG-PET/CT的有益辅助手段，以检测F-FDG-PET/CT未发现的病变并确定患者接受放射性配体治疗的资格。放射性标记的PSMA配体未来可能代表一种诊疗方法，对于少数选定且在既定治疗不再有效时进展时需要替代治疗选择的ATC和PDTC个体患者，其副作用较小。然而，由于我们样本量较小，需要进行更大规模的研究，以便对PSMA靶向诊断和治疗对ATC和PDTC的意义进行最终评估。
