Langbein Thomas, Kulkarni Harshad R, Schuchardt Christiane, Mueller Dirk, Volk Gerd Fabian, Baum Richard P
Theranostics Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka, 99438 Bad Berka, Germany.
Department of Nuclear Medicine, Technical University of Munich, Klinikum Rechts der Isar, 81675 Munich, Germany.
Diagnostics (Basel). 2022 Aug 10;12(8):1926. doi: 10.3390/diagnostics12081926.
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.
前列腺特异性膜抗原（PSMA）靶向放射性配体疗法（PRLT）是转移性去势抵抗性前列腺癌（mCRPC）患者一种很有前景的治疗选择。然而，放射性药物在唾液腺（SG）中的高摄取会导致口干症，并成为225Ac-PSMA-617的剂量限制因素。本研究调查了177Lu-PSMA-I&T/-617单药治疗以及联合使用225Ac-PSMA-617和177Lu-PSMA-617（串联PRLT）的唾液腺毒性。方法：对接受177Lu-PSMA-I&T/-617单药治疗或串联PRLT的三个患者队列进行回顾性分析。在一个短期队列（91例患者）中，在两个周期的177Lu-PSMA-I&T/-617治疗前后，进行了口干症评估（CTCAE v.5.0）、标准化问卷调查（sXI）、唾液腺闪烁显像（SGS）以及68Ga-PSMA-11-PET/CT上唾液腺的SUVmax和代谢体积（MV）测定。在一个长期队列中，对40例患者进行了类似检查。在一个串联队列中，对18例患者在一个周期的串联PRLT治疗后应用相同方案。结果：在短期随访中，22例（24.2%）患者出现1级口干症，sXI从7恶化至8（p<0.05）。在长期队列中，16例（40%）患者出现1至2级口干症。SGS未显示出显著变化，但所有唾液腺的MV均有所下降。在串联PRLT治疗后，12/18（66.7%）例患者报告有1至2级口干症，sXI从9.5显著恶化至14.0（p = 0.005），所有唾液腺的排泄分数（EF）和MV均显著降低。结论：177Lu-PSMA-I&T/-617仅引起轻微的唾液腺毒性，而一个周期的串联PRLT会导致显著的唾液腺损伤。这种标准化方案可能有助于客观化和量化唾液腺功能障碍。
