Rosar Florian, Neher Robert, Burgard Caroline, Linxweiler Johannes, Schreckenberger Mathias, Hoffmann Manuela A, Bartholomä Mark, Khreish Fadi, Ezziddin Samer
Department of Nuclear Medicine, Saarland University, 66421 Homburg, Germany.
Department of Urology, Saarland University, 66421 Homburg, Germany.
Cancers (Basel). 2022 Mar 26;14(7):1696. doi: 10.3390/cancers14071696.
In this study, we investigated upregulation of prostate-specific membrane antigen (PSMA) by enzalutamide in a cohort (n = 30) of patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Patients were examined by [68Ga]Ga-PSMA-11 PET/CT pre- and post-enzalutamide medication (mean 13 ± 7 days). Imaging results were compared based on quantification of whole-body PSMA tumor burden: total lesion PSMA (TLP) and normalized TLP values to liver (TLP-LR) and to parotid gland (TLP-PR). In addition, lesion-based analyses were performed. The median (mean) increases in TLP, TLP-LR and TLP-PR after enzalutamide medication were 10.1% (20.2%), 29.5% (34.8%) and 27.6% (24.4%), respectively. These increases were statistically significant (p = 0.002, p < 0.001, and p < 0.001), while prostate-specific antigen (PSA) serum values did not change significantly (p = 0.483). The increase was independent of prior patient exposure to enzalutamide. SUVmax increased substantially (>10%) in 49.6% of target lesions. The relative change was significantly higher in the subgroup of lesions with SUVmax < 10 (p < 0.001). In conclusion, short-term enzalutamide medication significantly increases PSMA expression in patients with mCRPC, irrespective of prior enzalutamide exposure. The relative PSMA upregulation effect seems to be more pronounced in lesions with only moderate baseline PSMA expression. Enzalutamide may provide a potential enhancer medication for PSMA-targeted radioligand therapy.
在本研究中，我们调查了恩杂鲁胺对一组（n = 30）晚期转移性去势抵抗性前列腺癌（mCRPC）患者前列腺特异性膜抗原（PSMA）的上调作用。在恩杂鲁胺用药前和用药后（平均13±7天），对患者进行了[68Ga]Ga-PSMA-11 PET/CT检查。基于全身PSMA肿瘤负荷的量化比较成像结果：总病变PSMA（TLP）以及TLP相对于肝脏（TLP-LR）和腮腺（TLP-PR）的标准化值。此外，还进行了基于病变的分析。恩杂鲁胺用药后，TLP、TLP-LR和TLP-PR的中位数（平均值）增加分别为10.1%（20.2%）、29.5%（34.8%）和27.6%（24.4%）。这些增加具有统计学意义（p = 0.002、p < 0.001和p < 0.001），而前列腺特异性抗原（PSA）血清值无显著变化（p = 0.483）。这种增加与患者先前是否接触过恩杂鲁胺无关。49.6%的靶病变SUVmax大幅增加（>10%）。SUVmax < 10的病变亚组中的相对变化显著更高（p < 0.001）。总之，短期恩杂鲁胺用药可显著增加mCRPC患者的PSMA表达，无论先前是否接触过恩杂鲁胺。相对PSMA上调效应似乎在基线PSMA表达仅为中等的病变中更为明显。恩杂鲁胺可能为PSMA靶向放射性配体治疗提供一种潜在的增强药物。
