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. 2022 Aug 10;12(8):1926.
doi: 10.3390/diagnostics12081926.

Salivary Gland Toxicity of PSMA-Targeted Radioligand Therapy with 177Lu-PSMA and Combined 225Ac- and 177Lu-Labeled PSMA Ligands (TANDEM-PRLT) in Advanced Prostate Cancer: A Single-Center Systematic Investigation

Thomas Langbein  1   2 , Harshad R Kulkarni  1   3 , Christiane Schuchardt  1 , Dirk Mueller  1   4 , Gerd Fabian Volk  5 , Richard P Baum  1   6
Affiliations

Salivary Gland Toxicity of PSMA-Targeted Radioligand Therapy with 177Lu-PSMA and Combined 225Ac- and 177Lu-Labeled PSMA Ligands (TANDEM-PRLT) in Advanced Prostate Cancer: A Single-Center Systematic Investigation

Thomas Langbein et al. Diagnostics (Basel). .

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.

Keywords: PSMA; mCRPC; radioligand therapy; salivary gland toxicity; xerostomia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patient cohorts and study workflow. * For the long-term cohort, data of sXI were only available at follow-up. EBRT = external beam radiotherapy; H&N = head and neck; PRLT = PSMA-targeted radioligand therapy.
Figure 2
Figure 2
Normal time–activity curves on salivary gland scintigraphy (left) detected by regions of interest (ROI) over the parotid and submandibular glands (right). Calculation of the excretion fraction (EF): U12–14/U18–20 = tracer uptake averaged from 12–14/18–20 min after tracer injection.
Figure 3
Figure 3
Relative decline of the metabolic volume (MV) of all 4 salivary glands during follow-up PET/CT compared to the baseline in the long-term cohort. (PG = parotid gland; SMG = submandibular gland).
Figure 4
Figure 4
Quantitative analysis of the salivary gland scintigraphy before and after 1 cycle of Tandem-PRLT. While the Umax of all salivary glands showed no significant changes (top), the EF declined significantly in all salivary glands (bottom). PG = parotid gland; SMG = submandibular gland. * Wilcoxon test.
Figure 5
Figure 5
SUVmax of the salivary glands at the baseline and follow-up PSMA PET/CT. PG = parotid gland; SMG = submandibular gland.
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