Kleiburg F, van der Hulle T, Gelderblom H, Slingerland M, Speetjens F M, Hawinkels L J A C, Dibbets-Schneider P, van Velden F H P, Pool M, Lam S W, Bovée J V M G, Heijmen L, de Geus-Oei L F
Biomedical Photonic Imaging Group, University of Twente, Enschede, The Netherlands.
Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Nucl Med Mol Imaging. 2025 Mar 27. doi: 10.1007/s00259-025-07224-z.
Prostate-specific membrane antigen (PSMA) expression has been observed in a subset of soft tissue sarcomas, mainly in the neovascular endothelial cells. This feasibility study aimed to evaluate PSMA expression and PSMA PET/CT imaging in metastatic soft tissue sarcoma, providing important insights for potential future exploration of PSMA-targeted radioligand therapy.
This prospective single-center study included adult patients with metastatic soft tissue sarcoma, with measurable disease (lesion diameter > 1 cm), available biopsy/resection material, ECOG/WHO performance status of 0-2 and either no prior systemic treatment, progressive disease during/after treatment, or stable disease/partial response with the last dose > 8 weeks prior. Immunohistochemical PSMA staining was performed on previously obtained biopsy or resection material. In case of high PSMA expression, a [F]-JK-PSMA-7 PET/CT scan evaluated tracer uptake, with adequate uptake defined as SUV > 8.
Of 25 included patients, 11 (44%) had high PSMA expression: 4/11 leiomyosarcomas, 3/4 dedifferentiated liposarcomas, 2/5 undifferentiated pleomorphic sarcomas, 1/2 myxofibrosarcomas and 1/1 malignant peripheral nerve sheath tumour. Five of 11 patients agreed to a [F]-JK-PSMA-7 PET/CT, of which 3 had lesions that showed adequate tracer uptake (SUV 10.7-16.7). However, uptake across all metastatic lesions was highly heterogeneous (median SUV = 3.8; range 0.5-16.7), indicating that these patients are unlikely to benefit sufficiently from PSMA-targeted therapy. The study was therefore terminated prematurely.
PSMA expression and PSMA tracer uptake in metastatic soft tissue sarcoma were highly heterogeneous. A deeper understanding of PSMA biology and improved patient selection criteria are essential for future application of PSMA-targeted radioligand therapy in this disease.
clinicaltrials.gov, NCT05522257. Registered 31-08-2022.
在一部分软组织肉瘤中观察到前列腺特异性膜抗原（PSMA）表达，主要存在于新生血管内皮细胞中。本可行性研究旨在评估转移性软组织肉瘤中PSMA的表达及PSMA PET/CT成像，为未来PSMA靶向放射性配体治疗的潜在探索提供重要见解。
这项前瞻性单中心研究纳入了患有转移性软组织肉瘤的成年患者，具有可测量的疾病（病灶直径>1 cm）、可用的活检/切除材料、ECOG/WHO体能状态为0 - 2，且既往未接受过全身治疗、治疗期间/治疗后疾病进展，或末次给药>8周前病情稳定/部分缓解。对先前获取的活检或切除材料进行PSMA免疫组织化学染色。若PSMA表达高，则进行[F]-JK-PSMA-7 PET/CT扫描以评估示踪剂摄取情况，摄取充分定义为SUV>8。
在纳入的25例患者中，11例（44%）PSMA表达高：11例平滑肌肉瘤中有4例、4例去分化脂肪肉瘤中有3例、5例未分化多形性肉瘤中有2例、2例黏液纤维肉瘤中有1例、1例恶性周围神经鞘瘤中有1例。11例患者中有5例同意进行[F]-JK-PSMA-7 PET/CT检查，其中3例病灶示踪剂摄取充分（SUV为10.7 - 16.7）。然而，所有转移病灶的摄取高度异质性（SUV中位数 = 3.8；范围0.5 - 16.7），表明这些患者不太可能从PSMA靶向治疗中充分获益。因此，该研究提前终止。
转移性软组织肉瘤中PSMA的表达及PSMA示踪剂摄取高度异质性。深入了解PSMA生物学特性并改进患者选择标准对于未来PSMA靶向放射性配体治疗在该疾病中的应用至关重要。
clinicaltrials.gov，NCT05522257。2022年8月31日注册。
