Department of Nuclear Medicine, School of Medicine, Technical University of Munich, 81675 München, Germany.
Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partnersite München, 69124 Heidelberg, Germany.
Int J Mol Sci. 2023 Nov 28;24(23):16845. doi: 10.3390/ijms242316845.
Most Prostate Specific Membrane Antigens (PSMAs) targeting small molecules accumulate in the salivary glands (SGs), raising concerns about SG toxicity, especially after repeated therapies or therapy with Ac-labeled ligands. SG toxicity is assessed clinically by the severity of patient-reported xerostomia, but this parameter can be challenging to objectively quantify. Therefore, we explored the feasibility of using SG volume as a biomarker for toxicity. In 21 patients with late-stage metastatic resistant prostate cancer (mCRPC), the PSMA volume and ligand uptake of SG were analyzed retrospectively before and after two cycles of Lu-PSMA (LuPSMA; cohort A) and before and after one cycle of Ac-PSMA-617 (AcPSMA, cohort B). Mean Volume-SG in cohort A was 59 ± 13 vs. 54 ± 16 mL (-10%, p = 0.4), and in cohort B, it was 50 ± 13 vs. 40 ± 11 mL (-20%, p = 0.007), respectively. A statistically significant decrease in the activity concentration in the SG was only observed in group B (SUV: 9.2 ± 2.8 vs. 5.3 ± 1.8, p < 0.0001; vs. A: SUV: 11.2 ± 3.3 vs. 11.1 ± 3.5, p = 0.8). SG volume and PSMA-ligand uptake are promising markers to monitor the SG toxicity after a PSMA RLT.
大多数靶向小分子的前列腺特异性膜抗原（PSMAs）在唾液腺（SGs）中积累，引起了对 SG 毒性的关注，尤其是在重复治疗或用 Ac 标记的配体治疗后。SG 毒性通过患者报告的口干严重程度进行临床评估，但这个参数难以客观量化。因此，我们探讨了使用 SG 体积作为毒性生物标志物的可行性。在 21 例晚期转移性去势抵抗性前列腺癌（mCRPC）患者中，回顾性分析了 Lu-PSMA（LuPSMA；A 队列）治疗前和治疗后两个周期以及 Ac-PSMA-617（AcPSMA，B 队列）治疗前和治疗后一个周期的 PSMA 体积和 SG 摄取。A 队列的平均 SG 体积为 59 ± 13 比 54 ± 16 mL（-10%，p = 0.4），B 队列为 50 ± 13 比 40 ± 11 mL（-20%，p = 0.007）。仅在 B 组观察到 SG 活性浓度的统计学显著下降（SUV：9.2 ± 2.8 比 5.3 ± 1.8，p < 0.0001；与 A 相比：SUV：11.2 ± 3.3 比 11.1 ± 3.5，p = 0.8）。SG 体积和 PSMA-配体摄取是监测 PSMA RLT 后 SG 毒性的有前途的标志物。
