Abstract:
Purpose: PSMA-targeted radioligand therapy (PRLT) is a promising treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, a high uptake of the radiopharmaceutical in the salivary glands (SG) can lead to xerostomia and becomes dose-limiting for 225Ac-PSMA-617. This study investigated the sialotoxicity of 177Lu-PSMA-I&T/-617 monotherapy and co-administered 225Ac-PSMA-617 and 177Lu-PSMA-617 (Tandem-PPRLT). Methods: Three patient cohorts, that had undergone 177Lu-PSMA-I&T/-617 monotherapy or Tandem-PRLT, were retrospectively analyzed. In a short-term cohort (91 patients), a xerostomia assessment (CTCAE v.5.0), a standardized questionnaire (sXI), salivary gland scintigraphy (SGS), and SG SUVmax and the metabolic volume (MV) on 68Ga-PSMA-11-PET/CT were obtained before and after two cycles of 177Lu-PSMA-I&T/-617. In a long-term cohort, 40 patients were similarly examined. In a Tandem cohort, the same protocol was applied to 18 patients after one cycle of Tandem-PRLT. Results: Grade 1 xerostomia in the short-term follow-up was observed in 22 (24.2%) patients with a worsening of sXI from 7 to 8 at (p < 0.05). In the long-term cohort, xerostomia grades 1 to 2 occurred in 16 (40%) patients. SGS showed no significant changes, but there was a decline of the MV of all SGs. After Tandem-PRLT, 12/18 (66.7%) patients reported xerostomia grades 1 to 2, and the sXI significantly worsened from 9.5 to 14.0 (p = 0.005), with a significant reduction in the excretion fraction (EF) and MV of all SGs. Conclusion: 177Lu-PSMA-I&T/-617 causes only minor SG toxicity, while one cycle of Tandem-PRLT results in a significant SG impairment. This standardized protocol may help to objectify and quantify SG dysfunction.
摘要:
目的:PSMA靶向放射性配体治疗(PRLT)是转移性去势抵抗性前列腺癌(mCRPC)患者的一种有希望的治疗选择。然而,唾液腺(SG)中放射性药物的高摄取可导致口干症,并成为225Ac-PSMA-617的剂量限制。本研究调查了177Lu-PSMA-I&T/-617单一疗法和共同施用225Ac-PSMA-617和177Lu-PSMA-617(串联-PPRLT)的唾液毒性。
方法:三个患者队列,经历过177Lu-PSMA-I&T/-617单一疗法或串联PRLT,进行回顾性分析。在短期队列中(91名患者),口干症评估(CTCAEv.5.0),标准化问卷(XI),唾液腺闪烁显像(SGS),在177Lu-PSMA-I和T/-617的两个周期之前和之后,获得了68Ga-PSMA-11-PET/CT上的SGSUVmax和代谢体积(MV)。在长期队列中,对40名患者进行了类似的检查。在串联队列中,对18例患者进行了一个周期的Tandem-PRLT治疗后采用相同的方案.
结果:在短期随访中,在22例(24.2%)患者中观察到1级口干症,sXI从7到8(p结论:177Lu-PSMA-I&T/-617仅引起轻微的SG毒性,而一个周期的串联-PRLT导致显著的SG损害。该标准化方案可能有助于对SG功能障碍进行客观化和量化。