Salivary Gland Toxicity of PSMA Radioligand Therapy: Relevance and Preventive Strategies

Langbein, Thomas; Chaussé, Guillaume; Baüm, Richard

doi:10.2967/jnumed.118.214379

Cited by 80 publications

(70 citation statements)

References 17 publications

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“…(a) 68 Ga-PSMA-11 PET/CTcannot evaluate the excretion function of salivary glands. ere is no effective method to reduce PSMA ligand uptake in salivary glands [26]. Further research is warranted.…”

Section: Discussionmentioning

confidence: 99%

Potential Applications of ⁶⁸Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with ^99mTcO₄⁻ Salivary Gland Scintigraphy

Zhao

Xia

Liu

et al. 2020

Contrast Media & Molecular Imaging

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Purpose. To preliminarily evaluate the feasibility and potential of using 68Ga-PSMA-11 PET/CT in evaluating the function of salivary glands and lacrimal glands in comparison with 99mTc-pertechnetate (T99mcO4−) salivary gland scintigraphy (SGS). Methods. A retrospective study was performed in 15 patients with different degrees of xerostomia and suspected salivary gland dysfunction. Each patient underwent 68Ga-PSMA-11 PET/CT first and SGS the next day, and the findings of both scans were compared. Results. The results of 68Ga-PSMA-11 PET/CT and SGS were consistent in 12/15 patients (80%) and were inconsistent in the remaining patients (20%). For 5 (33.3%) of 15 patients, 68Ga-PSMA-11 PET/CT provided more information than did SGS. Additionally, 68Ga-PSMA-11 PET/CT corrected the misdiagnosis by SGS for 1 patient. Conclusions. 68Ga-PSMA-11 PET/CT is a potentially useful imaging tool for evaluating the function of salivary glands and lacrimal glands. 68Ga-PSMA-11 PET/CT can be a promising supplement to SGS, and its clinical value deserves further study.

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Section: Discussionmentioning

confidence: 99%

Potential Applications of ⁶⁸Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with ^99mTcO₄⁻ Salivary Gland Scintigraphy

Zhao

Xia

Liu

et al. 2020

Contrast Media & Molecular Imaging

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“…On the other hand, 177 Lu-PSMA-617 has a long half-life, and uptake of 177 Lu-PSMA-617 from the interstitial or intracellular space into the salivary glands is relatively slow (7). Apart from these considerations, labeling of PSMA-targeting antibodies such as J591 instead of small molecules such as PSMA-617 (molecular weight, 150 vs. 1.4 kD, respectively) might be able to lower the PSMA uptake and decrease the risk of sialotoxicity (25,50,51).…”

Section: Discussionmentioning

confidence: 99%

“…Local application of cold compounds or inhibitors of PSMA, such as 2-(phosphonomethyl) pentanedioic acid, has been also investigated (54). Because of the high blood supply of the PGs, systemic absorption from intraparenchymal application of 2-(phosphonomethyl)pentanedioic acid may cause potential inhibition of PSMA-targeted tumor cells, which needs further consideration (25). Gene and stem cell therapy has been suggested to prevent xerostomia and may soon solve the problem (24).…”

Section: Discussionmentioning

confidence: 99%

“…The salivary glands are radiosensitive organs, and physiologic high binding of PSMA ligands may cause undesirable side effects (19,24). Xerostomia, a frequent but mild to moderate side effect after PRLT of mCRPC, decreases the patient's quality of life (19,(25)(26)(27). One suggestion has been the use of external cooling to bring about vasoconstriction, reduce blood flow, decrease PSMA binding, and thus prevent radiation toxicity to the salivary glands (5,14,16,18,(28)(29)(30)(31)(32).…”

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confidence: 99%

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Effect of External Cooling on ¹⁷⁷Lu-PSMA Uptake by the Parotid Glands

et al. 2019

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Recent years have seen the start of treatment of metastatic castration-resistant prostate cancer with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT), especially 177 Lu-PSMA-617. However, PRLT has side effects on the salivary glands that limit the safety of the treatment. The current study aimed to show the effect of external cooling with ice packs on 177 Lu-PSMA-617 uptake by the parotid glands (PGs). Methods:The study included 19 patients (mean age, 72.9 y) with metastatic castration-resistant prostate cancer who had been referred for the first time for 177 Lu-PSMA-617 treatment and underwent pretreatment 68 Ga-PSMA-11 PET/CT. Before the initiation of PRLT, the SUV max and SUV mean of the right and left PGs were measured on 68 Ga-PSMA PET/CT. Frozen ice packs were then affixed over the right PG of each patient for approximately 5 h; 1 h after they were affixed, PRLT was administered. At 4 h after PRLT, head-and-neck SPECT/CT was performed, and at both 4 and 24 h after PRLT, whole-body planar scintigraphy was performed. Regions and volumes of interest were applied for the right and left PGs, and the counts and volumes were determined. Results: Before PRLT, 68 Ga-PSMA-11 PET/CT showed no significant difference in SUV max or SUV mean between the right and left PGs (P . 0.05). At 4 and 24 h after PRLT, planar imaging showed no significant difference in counts between the cooled and noncooled PGs (P . 0.05). Furthermore, at 4 h after PRLT, SPECT/CT showed no significant difference in counts or volumes between the cooled and noncooled PGs (P . 0.05). Conclusion: External cooling does not reduce uptake of 177 Lu-PSMA-617 by the PGs.

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“…When patients with metastatic castration-resistant prostate cancer were treated with the a-emitting 225 Ac-PSMA-617, full biochemical responses were observed in some patients, even in those who had not responded to treatment with 177 Lu-PSMA-617 (11). However, severe and irreversible xerostomia significantly limits the potential utility of this promising approach (13).…”

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confidence: 99%

A Single Dose of ²²⁵Ac-RPS-074 Induces a Complete Tumor Response in an LNCaP Xenograft Model

et al. 2018

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Promising biochemical responses to 225 Ac-prostate-specific membrane antigen (PSMA) 617, even in patients who are refractory to βparticle radiation, illustrate the potential of targeted α-therapy for the treatment of metastatic castration-resistant prostate cancer. However, side effects such as xerostomia are severe and irreversible. To fully harness the potential of targeted α-therapy, it is necessary to increase the therapeutic index of the targeted radioligands. One emerging strategy is to increase clearance half-life through enhanced binding to serum albumin. We have evaluated the albumin-binding PSMA-targeting ligand RPS-074 in a LNCaP xenograft model to determine its potential value to the treatment of prostate cancer. Methods: 225 Ac-RPS-074 was evaluated in male BALB/c mice bearing LNCaP xenograft tumors. A biodistribution study was performed over 21 d to determine the dosimetry in tumors and normal tissue. The dose response was measured in groups of 7 mice using 37, 74, and 148 kBq of 225 Ac-RPS-074 and compared with positive and negative control groups. Mice were sacrificed when tumor volume exceeded 1,500 mm 3 . Results: 225 Ac-RPS-074 was labeled in greater than 98% radiochemical yield and showed high (.10% injected dose/g) and sustained accumulation in LNCaP tumors from 24 h to beyond 14 d. Signal in blood and highly vascularized tissues was evident over the first 24 h after injection and cleared by 7 d. The tumor-tokidney ratio was 4.3 ± 0.7 at 24 h and 62.2 ± 9.5 at 14 d. A single injection of 148 kBq induced a complete response in 6 of 7 tumors, with no apparent toxic effects. Treatment with 74 kBq induced a partial response in 7 of 7 tumors, but from 42 d, 6 of 7 experienced significant regrowth. The 37-kBq group experienced a survival benefit relative to the negative control but not compared with the positive control group. Conclusion: A single dose of 148 kBq of 225 Ac-RPS-074 induced a complete response in 86% of tumors, with tumor-to-normal-tissue ratios that predict an improved therapeutic index. The use of the macropa chelator enabled quantitative radiolabeling and may facilitate the clinical translation of this promising targeted α-therapeutic. Ac-RPS-074 Induces a Complete Tumor Response in an LNCaP 225 A Single Dose of http://jnm.snmjournals.org/content/60/5/649 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml

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Salivary Gland Toxicity of PSMA Radioligand Therapy: Relevance and Preventive Strategies

Cited by 80 publications

References 17 publications

Potential Applications of ⁶⁸Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with ^99mTcO₄⁻ Salivary Gland Scintigraphy

Potential Applications of ⁶⁸Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with ^99mTcO₄⁻ Salivary Gland Scintigraphy

Effect of External Cooling on ¹⁷⁷Lu-PSMA Uptake by the Parotid Glands

A Single Dose of ²²⁵Ac-RPS-074 Induces a Complete Tumor Response in an LNCaP Xenograft Model

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Salivary Gland Toxicity of PSMA Radioligand Therapy: Relevance and Preventive Strategies

Cited by 80 publications

References 17 publications

Potential Applications of 68Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with 99mTcO4− Salivary Gland Scintigraphy

Potential Applications of 68Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with 99mTcO4− Salivary Gland Scintigraphy

Effect of External Cooling on 177Lu-PSMA Uptake by the Parotid Glands

A Single Dose of 225Ac-RPS-074 Induces a Complete Tumor Response in an LNCaP Xenograft Model

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Potential Applications of ⁶⁸Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with ^99mTcO₄⁻ Salivary Gland Scintigraphy

Potential Applications of ⁶⁸Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with ^99mTcO₄⁻ Salivary Gland Scintigraphy

Effect of External Cooling on ¹⁷⁷Lu-PSMA Uptake by the Parotid Glands

A Single Dose of ²²⁵Ac-RPS-074 Induces a Complete Tumor Response in an LNCaP Xenograft Model