Renal and Salivary Gland Functions after Three Cycles of PSMA-617 Therapy Every Four Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Abstract

Background: [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [68Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran’s Q test were applied to assess organ toxicity. Results: In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly (p < 0.05). Conclusion: Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks.

Assessment of salivary gland function after 177Lu-PSMA radioligand therapy: Current concepts in imaging and management

“…Only few studies with small patient cohort used scintigraphy for objective assessment of salivary gland function (8–12 weeks after treatment) that showed no significant change from baseline [ 21 , 29 ]. The incidence of salivary gland toxicity was often reported to be below 37% when prevention techniques such as good hydration and/or external cooling were used to prevent salivary gland damage ( Table 1 ) [ 22 , 23 , 29 ].…”

“… Yes/No Thomson et al. [29] (S1) My mouth feels dry. (S2) I have difficulty in eating dry foods (S3) I get up at night to drink.…”

“…Table 1 details the relevant findings from major studies, focusing on side effects related to salivary gland function. The symptoms of salivary gland toxicity with 177 Lu-PSMA RLT were reported to be mild and transient, mostly based on clinical assessment, though the rates of developing symptoms such as dryness of mouth and hypogeusia were found to be highly variable, ranging between 20 and 60% [ 13 , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] ]. Only few studies with small patient cohort used scintigraphy for objective assessment of salivary gland function (8–12 weeks after treatment) that showed no significant change from baseline [ 21 , 29 ].…”

“…The symptoms of salivary gland toxicity with 177 Lu-PSMA RLT were reported to be mild and transient, mostly based on clinical assessment, though the rates of developing symptoms such as dryness of mouth and hypogeusia were found to be highly variable, ranging between 20 and 60% [ 13 , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] ]. Only few studies with small patient cohort used scintigraphy for objective assessment of salivary gland function (8–12 weeks after treatment) that showed no significant change from baseline [ 21 , 29 ]. The incidence of salivary gland toxicity was often reported to be below 37% when prevention techniques such as good hydration and/or external cooling were used to prevent salivary gland damage ( Table 1 ) [ 22 , 23 , 29 ].…”

Discovery of Glutamate Carboxypeptidase III Ligands to Compete the Uptake of [177Lu]Lu-PSMA-617 in Healthy Organs

“…A substantial proportion of patients enrolled in the VISION trial had to discontinue the treatment due to adverse events (i.e., mainly long-lasting xerostomia, also called “dry mouth” effect) . The dose-limiting side effects have been associated with the uptake of PSMA ligands in healthy tissue. , As observed in imaging procedures, [ 177 Lu]Lu-PSMA-617 localizes to salivary glands and kidneys. Various strategies to reduce the uptake of PSMA ligands in healthy organs have been proposed and investigated, with the aim to facilitate the administration of radiolabeled PSMA ligands at higher doses to increase therapeutic efficacy.…”