McAllister Brenna C, Mesbahi Nooshin, Dodson Esther E, Abdulsalam Sakinah, Berkman Clifford E, Caromile Leslie A
Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT, United States.
Department of Chemistry, Washington State University, Pullman, WA, United States.
Front Oncol. 2024 Nov 15;14:1504514. doi: 10.3389/fonc.2024.1504514. eCollection 2024.
Giant cell tumor of bone (GCTB) is a rare bone tumor often necessitating surgical intervention, radiation therapy, or treatment with bisphosphonates or denosumab. Tc-MDP bone scintigraphy for GCTB has limited specificity, and the relatively high uptake of F-FDG in GCTB makes it challenging to differentiate it from other benign bone tumors. More specific detection and treatment modalities for GCTB are needed to enhance patient monitoring and outcomes. Prostate Specific Membrane Antigen (PSMA) is present in the neovasculature of various tumors, yet unexplored in GCTB. PSMA-targeted imaging and radiotherapeutic agents Locametz and Pluvicto are a powerful theranostic pair for detecting and treating PSMA-positive metastatic tumors, including those in bone, and thus have considerable potential to be repurposed for GCTB. This study aimed to determine if the vasculature of GCTB was PSMA-positive and whether targeting it with PSMA-specific agents was feasible. Using bone core samples from 28 GCTB patients and 9 negative controls, we present the first robust detection of PSMA on the tumor vasculature of GCTB. To demonstrate the potential repurposed use of PSMA-targeted agents in detecting and treating GCTB, we used a PSMA-specific fluorescent probe (FAM-C6-1298) as a model for these radiopharmaceutical agents. Incubation of fresh GCTB tissue samples with FAM-C6-1298 showed increased fluorescence intensity compared to controls, indicating successful targeting of PSMA in GCTB tissue. In conclusion, our data established that PSMA is not only present in the tumor vasculature of GCTB patient tissue but can be effectively targeted with repurposed PSMA-specific radiopharmaceuticals for diagnosis and therapy.
骨巨细胞瘤（GCTB）是一种罕见的骨肿瘤，通常需要手术干预、放射治疗或使用双膦酸盐或地诺单抗进行治疗。用于GCTB的锝-亚甲基二膦酸盐（Tc-MDP）骨闪烁显像特异性有限，且GCTB中氟代脱氧葡萄糖（F-FDG）摄取相对较高，这使得将其与其他良性骨肿瘤区分开来具有挑战性。需要更具特异性的GCTB检测和治疗方式，以加强对患者的监测并改善治疗结果。前列腺特异性膜抗原（PSMA）存在于各种肿瘤的新生血管中，但在GCTB中尚未得到研究。PSMA靶向成像和放射治疗药物Locametz和Pluvicto是用于检测和治疗PSMA阳性转移性肿瘤（包括骨转移瘤）的强大诊疗组合，因此具有用于GCTB的巨大潜力。本研究旨在确定GCTB的血管是否为PSMA阳性，以及用PSMA特异性药物靶向治疗是否可行。我们使用来自28例GCTB患者的骨芯样本和9个阴性对照，首次有力地检测到GCTB肿瘤血管上的PSMA。为了证明PSMA靶向药物在检测和治疗GCTB方面的潜在新用途，我们使用PSMA特异性荧光探针（FAM-C6-1298）作为这些放射性药物的模型。与对照组相比，新鲜GCTB组织样本与FAM-C6-1298孵育后荧光强度增加，表明PSMA在GCTB组织中成功被靶向。总之，我们的数据表明，PSMA不仅存在于GCTB患者组织的肿瘤血管中，而且可以用重新利用的PSMA特异性放射性药物有效靶向，用于诊断和治疗。
