在胶质母细胞瘤中已经描述了前列腺特异性膜抗原（PSMA）在新生血管中的上调表达，而非受影响的脑血管几乎没有PSMA的表达。目前尚不清楚PET中PSMA靶向示踪器摄取是基于PSMA特异性结合新生血管还是肿瘤中非特异性摄取。在本研究中，我们量化了不同PSMA靶向示踪器在胶质母细胞瘤中的摄取情况，并将其与同一患者的肿瘤活检样本中的PSMA表达进行了相关性分析。方法：14例新发（n = 8）或复发（n = 6）胶质母细胞瘤患者接受了术前PET扫描，注射1.5 MBq/kg[68Ga]Ga-PSMA-11（n = 7），200 MBq的[18F]DCFpyl（n = 3）或200 MBq的[18F]PSMA-1007（n = 4）。确定了肿瘤的摄取量和肿瘤与背景的比率，以对侧未受影响的脑组织作为背景。在部分患者中，使用免疫组织化学（n = 35）或RNA测序（n = 13）确定的肿瘤组织样本（n = 40）的PSMA表达水平与PET中的示踪剂摄取进行了相关性分析。结果：无论使用何种示踪剂，所有肿瘤中均发现中等至高度（SUVmax, 1.3-20.0）的异质性摄取。未受影响的脑组织中的摄取量较低，导致肿瘤与背景的比率高（6.1-359.0），该比率通过将肿瘤的SUVmax除以背景的SUVmax进行计算。免疫组织化学显示肿瘤微血管内皮细胞上的PSMA表达存在变异，同时也在散在的未知来源的个体细胞和神经纤维间存在颗粒状染色。在体内摄取和PSMA表达水平之间未发现相关性（对于免疫组织化学，r = -0.173, P = 0.320；对于RNA测序，r = -0.033, P = 0.915）。结论：我们的结果显示了不同PSMA靶向示踪剂在胶质母细胞瘤中的潜在应用价值。然而，我们发现免疫组织化学中的PSMA表达水平与PET中的摄取强度之间没有相关性。是否可以解释这一现象，例如免疫组织化学无法测量功能活跃的PSMA、示踪剂的药代动力学或破坏的血脑屏障对示踪剂滞留的贡献等仍需进一步研究。© 2023年核医学与分子显像学会所所有。

Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo (n = 8) or recurrent (n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [68Ga]Ga-PSMA-11 (n = 7), 200 MBq of [18F]DCFpyl (n = 3), or 200 MBq of [18F]PSMA-1007 (n = 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples (n = 40), determined using immunohistochemistry (n = 35) or RNA sequencing (n = 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUVmax, 1.3-20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1-359.0) calculated by dividing SUVmax of tumor by SUVmax of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between in vivo uptake and PSMA expression levels (for immunohistochemistry, r = -0.173, P = 0.320; for RNA, r = -0.033, P = 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodologic reasons, such as the inability to measure functionally active PSMA with immunohistochemistry, tracer pharmacokinetics, or the contribution of a disturbed blood-brain barrier to tracer retention, should still be investigated.© 2023 by the Society of Nuclear Medicine and Molecular Imaging.