¹⁷⁷Lu-PSMA-617 radioligand therapy (RLT) has evolved as a suitable alternative to existing therapeutic options in patients with metastatic castration-resistant prostate cancer. With the emergence of -emitters such as 225Ac, the efficacy of PSMA-RLT has further improved. Xerostomia and myelosuppression are common early treatment-emergent adverse events in patients receiving this therapy.

¹⁷⁷Lu-PSMA-617 radioligand therapy (RLT) has evolved as a suitable alternative to existing therapeutic options in patients with metastatic castration-resistant prostate cancer. With the emergence of -emitters such as 225Ac, the efficacy of PSMA-RLT has further improved. Xerostomia and myelosuppression are common early treatment-emergent adverse events in patients receiving this therapy.

Salivary gland dysfunction after ¹⁷⁷Lu-PSMA-I&T/-617 PRLT has minor clinical relevance, both subjectively and objectively. Even after high cumulative activities, only mild-to-moderate dryness of mouth occurs in a minority of the patients. The prevalence of xerostomia appears to be significantly lower than the historical controls after external radiotherapy, radioiodine therapy, and especially after PRLT with 225Ac-PSMA-617. A validated questionnaire on xerostomia, salivary gland scintigraphy, and PSMA-PET/CT parameters can help to objectify, standardize, and quantify the SG toxicity of PRLT. A decrease of the excretion fraction on SGS and of the metabolic volume on PSMA PET/CT can be early indicators of SG impairment. The co-administration of lower doses of 225Ac in combination with ¹⁷⁷Lu-PSMA-617 (Tandem concept) can decrease severe xerostomia after PRLT with alpha-emitters.

Salivary gland dysfunction after ¹⁷⁷Lu-PSMA-I&T/-617 PRLT has minor clinical relevance, both subjectively and objectively. Even after high cumulative activities, only mild-to-moderate dryness of mouth occurs in a minority of the patients. The prevalence of xerostomia appears to be significantly lower than the historical controls after external radiotherapy, radioiodine therapy, and especially after PRLT with 225Ac-PSMA-617. A validated questionnaire on xerostomia, salivary gland scintigraphy, and PSMA-PET/CT parameters can help to objectify, standardize, and quantify the SG toxicity of PRLT. A decrease of the excretion fraction on SGS and of the metabolic volume on PSMA PET/CT can be early indicators of SG impairment. The co-administration of lower doses of 225Ac in combination with ¹⁷⁷Lu-PSMA-617 (Tandem concept) can decrease severe xerostomia after PRLT with alpha-emitters.

Salivary gland dysfunction after ¹⁷⁷Lu-PSMA-I&T/-617 PRLT has minor clinical relevance, both subjectively and objectively. Even after high cumulative activities, only mild-to-moderate dryness of mouth occurs in a minority of the patients. The prevalence of xerostomia appears to be significantly lower than the historical controls after external radiotherapy, radioiodine therapy, and especially after PRLT with 225Ac-PSMA-617. A validated questionnaire on xerostomia, salivary gland scintigraphy, and PSMA-PET/CT parameters can help to objectify, standardize, and quantify the SG toxicity of PRLT. A decrease of the excretion fraction on SGS and of the metabolic volume on PSMA PET/CT can be early indicators of SG impairment. The co-administration of lower doses of 225Ac in combination with ¹⁷⁷Lu-PSMA-617 (Tandem concept) can decrease severe xerostomia after PRLT with alpha-emitters.

Salivary gland dysfunction after ¹⁷⁷Lu-PSMA-I&T/-617 PRLT has minor clinical relevance, both subjectively and objectively. Even after high cumulative activities, only mild-to-moderate dryness of mouth occurs in a minority of the patients. The prevalence of xerostomia appears to be significantly lower than the historical controls after external radiotherapy, radioiodine therapy, and especially after PRLT with 225Ac-PSMA-617. A validated questionnaire on xerostomia, salivary gland scintigraphy, and PSMA-PET/CT parameters can help to objectify, standardize, and quantify the SG toxicity of PRLT. A decrease of the excretion fraction on SGS and of the metabolic volume on PSMA PET/CT can be early indicators of SG impairment. The co-administration of lower doses of 225Ac in combination with ¹⁷⁷Lu-PSMA-617 (Tandem concept) can decrease severe xerostomia after PRLT with alpha-emitters.

Salivary gland dysfunction after ¹⁷⁷Lu-PSMA-I&T/-617 PRLT has minor clinical relevance, both subjectively and objectively. Even after high cumulative activities, only mild-to-moderate dryness of mouth occurs in a minority of the patients. The prevalence of xerostomia appears to be significantly lower than the historical controls after external radiotherapy, radioiodine therapy, and especially after PRLT with 225Ac-PSMA-617. A validated questionnaire on xerostomia, salivary gland scintigraphy, and PSMA-PET/CT parameters can help to objectify, standardize, and quantify the SG toxicity of PRLT. A decrease of the excretion fraction on SGS and of the metabolic volume on PSMA PET/CT can be early indicators of SG impairment. The co-administration of lower doses of 225Ac in combination with ¹⁷⁷Lu-PSMA-617 (Tandem concept) can decrease severe xerostomia after PRLT with alpha-emitters.

Paragangliomas can metastasize, posing potential challenges in both symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and ¹⁷⁷Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another one. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. As conclusion, perspectives in radiotherapies of paraganglioma patients are outlined since they hold near future promising approaches that can improve patient outcomes.

Paragangliomas can metastasize, posing potential challenges in both symptomatic management and disease control. Systemic targeted radiotherapies using 131I-MIBG and ¹⁷⁷Lu-DOTATATE are a mainstay in the treatment of metastatic paragangliomas. This clinical scenario and discussion aim to enhance physicians' knowledge of the stepwise approach to treat these patients with paraganglioma targeted radiotherapies. It comprehensively discusses current approaches to selecting paraganglioma patients for targeted radiotherapies and how to choose between the two radiotherapies based on specific patient and tumor characteristics, when either therapy is feasible, or one is superior to another one. The safety, efficacy, toxicity profiles, and optimization of these radiotherapies are also discussed, along with other therapeutic options including radiotherapies, available for patients besides these two therapies. As conclusion, perspectives in radiotherapies of paraganglioma patients are outlined since they hold near future promising approaches that can improve patient outcomes.