INTRODUCTION A new therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) of heavily pre-treated patients lies in 177Lu-PSMA-617 radioligand therapy. METHODS On the basis of PSMA-targeted 68Ga-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for 177Lu-PSMA-617 therapy (6 GBq/cycle, 2 to 6 cycles, 6-10 weeks apart) and followed until death. Post-therapy whole-body (WB) dosimetry and 68Ga-PSMA-11 PET/CT data were compared and related to progression free and overall survival. RESULTS 177Lu-PSMA-617 dosimetry after the first cycle indicated high tumor doses for skeletal (4.01 ± 2.64; range 1.10-13.00 Gy/GBq), lymph node (3.12 ± 2.07; range 0.70-8.70 Gy/GBq), and liver (2.97 ± 1.38; range 0.76-5.00 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 24 GBq. Any PSA decrease after the first cycle was found in 23/32 (72%), after the second cycle in 22/32 (69%), after the third cycle in 16/28 (57%), and after the fourth cycle in 8/18 (44%) patients. Post-therapy 24 h WB scintigraphy showed decreased tumor-to-background ratios in 24/32 (75%) after the first therapy cycle, after the second cycle in 17/29 (59%), and after the third cycle in 13/21 (62%) patients. The median PFS was 7 months and the median OS 12 months. In the group of PSA responders (n = 22) the median OS was 17 months versus 11 months in the group of non-responders (n = 10), p < 0.05. Decreasing SUVmax values were found for parotid (15.93 ± 6.23 versus 12.33 ± 4.07) and submandibular glands (17.65 ± 7.34 versus 13.12 ± 4.62) following treatment, along with transient (n = 6) or permanent (n = 2) xerostomia in 8/32 (25%) patients. In 3/32 patients, nephrotoxicity changed from Grade 2 to 3, whereas neither Grade 4 nephrotoxicity nor hematotoxicity was found. In most patients a good agreement was observed for the visual interpretation of the tracer accumulation between 24 h WB and PET/CT scans. However, no significance could be calculated for baseline-absorbed tumor doses and SUVmax values of tumor lesions. 5/32 (16%) patients showed a mixed response pattern, which resulted in disease progression over time. CONCLUSION Serial PSA measurements and post-therapy 24 h WB scintigraphy seems to allow a sufficiently accurate follow-up of 177Lu-PSMA-617-treated mCRPC patients whereas 68Ga-PSMA-11 PET/CT should be performed for patient selection and final response assessment.

中文翻译：

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在转移性去势抵抗性前列腺癌的PSMA靶向中使用68Ga / 177Lu鼻窦镜概念：治疗后全身闪烁显像在随访中的影响。

引言177Lu-PSMA-617放射性配体疗法是对大量接受过预处理的患者进行转移性去势抵抗性前列腺癌（mCRPC）的新治疗选择。方法基于PSMA靶向的68Ga-PSMA-11 PET / CT，选择32例连续的mCRPC患者进行177Lu-PSMA-617治疗（6 GBq /周期，2至6个周期，间隔6-10周），并随访至死亡。比较了治疗后全身剂量（WB）和68Ga-PSMA-11 PET / CT数据，这些数据与无进展生存期和总体生存率相关。结果第一个周期后的177Lu-PSMA-617剂量表明骨骼，淋巴结（3.12±2.07;范围0.70-8.70 Gy / GBq）和肝脏（4.01±2.64;范围1.10-13.00 Gy / GBq）高肿瘤剂量。 2.97±1.38；范围0.76-5。00 Gy / GBq）转移，而所有患者的组织/器官剂量为24 GBq的意向治疗活性。在第一个循环后的PSA下降在23/32（72％），第二个循环后在22/32（69％），在第三个循环后在16/28（57％）和在第四个循环后8/18（44％）患者。治疗后24小时WB闪烁显像显示，在第一个治疗周期后，24/32（75％），第二个周期后17/29（59％）和第三个周期后13/24中，肿瘤与背景的比率降低。 21名（62％）患者。PFS中位数为7个月，OS中位数为12个月。PSA应答组（n = 22）中位OS为17个月，而无应答组（n = 10）为11个月，p <0.05。发现腮腺（15.93±6.23对12.33±4.07）和下颌下腺（17.65±7）的SUVmax值降低。34 / 13.12±4.62），以及8/32（25％）患者的暂时性（n = 6）或永久性（n = 2）口腔干燥症。在3/32例患者中，肾毒性从2级变为3级，而4级肾毒性和血液毒性均未发现。在大多数患者中，对24 h WB和PET / CT扫描之间示踪剂积累的视觉解释观察到了很好的一致性。但是，对于基线吸收的肿瘤剂量和肿瘤病变的SUVmax值，无法计算出显着性。5/32（16％）患者显示出不同的反应模式，导致疾病随时间发展。