PURPOSE There is preliminary evidence for prostate-specific membrane antigen (PSMA) upregulation effects of androgen receptor blockade in prostate cancer. In an attempt to find the best condition for PSMA radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC) patients, we evaluated the effect of oral enzalutamide in patients, predominantly having previously progressed on enzalutamide treatment. METHODS Ten patients with advanced mCRPC scheduled for PSMA radioligand therapy were examined with 68Ga-PSMA-11 PET/CT before and after a mean of 11.8 days of enzalutamide 160 mg/day. Imaging results were compared using total PSMA tumor burden quantification. We assessed whole-body total lesion PSMA (TLP), defined as SUVmean × tumor volume and calculated TLP-to-liver ratio (TLP-LR), TLP-to-parotid gland ratio (TLP-PR), and TLP-to-kidney ratio (TLP-KR). RESULTS The mean (median) increase of TLP-LR, TLP-PR, and TLP-KR in the cohort was 49.3% (38.8%), 45.1% (23.5%), and 54.9% (37.6%), respectively. These increases were statistically significant (p = 0.002, p = 0.014, and p = 0.014), while PSA values did not change significantly (p = 0.846). Seven of the 10 patients had previously undergone enzalutamide treatment with eventual progression, formally classified as treatment failure. No side effects were noted in the short term. CONCLUSIONS Our results suggest that enzalutamide could be considered as a PSMA radioligand treatment enhancing primer medication, which may increase PSMA expression by a dimension of 50% in mCRPC. The effect was shown even in patients having previously failed enzalutamide treatment for arrest of progression in the mCRPC setting. Our observation deserves evaluation in a prospective setting.

中文翻译：

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通过雄激素受体阻滞上调肿瘤PSMA表达的范式的新见解：即使在先前接受恩杂鲁胺治疗的患者中，恩杂鲁胺也可诱导去势抵抗性前列腺癌中PSMA上调。

目的有初步证据表明雄激素受体阻滞在前列腺癌中具有前列腺特异性膜抗原（PSMA）上调作用。为了寻找在转移性去势抵抗性前列腺癌（mCRPC）患者中进行PSMA放射配体治疗的最佳条件，我们评估了口服enzalutamide对患者的影响，主要是在enzalutamide治疗方面取得了进展。方法在平均11.8天恩杂鲁胺160毫克/天的前后，用68Ga-PSMA-11 PET / CT检查10例计划进行PSMA放射配体治疗的晚期mCRPC患者。使用总PSMA肿瘤负荷定量比较影像学结果。我们评估了全身总病变PSMA（TLP），定义为SUVmean×肿瘤体积，并计算了TLP-肝比（TLP-LR），TLP-腮腺比（TLP-PR），和TLP与肾脏的比率（TLP-KR）。结果队列中TLP-LR，TLP-PR和TLP-KR的平均（中位数）增长分别为49.3％（38.8％），45.1％（23.5％）和54.9％（37.6％）。这些增加具有统计学意义（p = 0.002，p = 0.014和p = 0.014），而PSA值没有显着变化（p = 0.846）。10例患者中有7例曾接受enzalutamide治疗，最终进展为正式治疗失败。短期内未发现副作用。结论我们的结果表明，enzalutamide可以被视为增强PSMA放射配体治疗的引物药物，在mCRPC中可以使PSMA表达增加50％。甚至在以前因enzalutamide治疗失败而停止mCRPC病情进展的患者中也显示出了这种效果。