Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy

Satapathy, Sujata; Sharma, Vishal; Sood, Anil K.; Maheshwari, Pooja; Gill, Harinder Jit Singh

doi:10.1097/rlu.0000000000004149

Cited by 8 publications

(5 citation statements)

References 8 publications

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“…An increased risk of acute nephrotoxicity after application of [ 225 Ac]Ac-SibuDAB as compared to [ 225 Ac]Ac-PSMA-617 was not identified under the given experimental conditions. It has to be critically acknowledged, however, that radionephropathy in patients is commonly observed later than two months after administration of the radioligand [ 9 , 36 ]. Although the manifestations may occur earlier in mice than in humans, delayed radiotoxic effects cannot be excluded based on the data presented in this study.…”

Section: Resultsmentioning

confidence: 99%

[225Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [225Ac]Ac-PSMA-617

Busslinger

Tschan

Richard³

et al. 2022

Cancers

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In the present study, SibuDAB, an albumin-binding PSMA ligand, was investigated in combination with actinium-225 and the data were compared with those of [225Ac]Ac-PSMA-617. In vitro, [225Ac]Ac-SibuDAB and [225Ac]Ac-PSMA-617 showed similar tumor cell uptake and PSMA-binding affinities as their 177Lu-labeled counterparts. The in vitro binding to serum albumin in mouse and human blood plasma, respectively, was 2.8-fold and 1.4-fold increased for [225Ac]Ac-SibuDAB as compared to [177Lu]Lu-SibuDAB. In vivo, this characteristic was reflected by the longer retention of [225Ac]Ac-SibuDAB in the blood than previously seen for [177Lu]Lu-SibuDAB. Similar to [225Ac]Ac-PSMA-617, [225Ac]Ac-SibuDAB was well tolerated at 30 kBq per mouse. Differences in blood cell counts were observed between treated mice and untreated controls, but no major variations were observed between values obtained for [225Ac]Ac-SibuDAB and [225Ac]Ac-PSMA-617. [225Ac]Ac-SibuDAB was considerably more effective to treat PSMA-positive tumor xenografts than [225Ac]Ac-PSMA-617. Only 5 kBq per mouse were sufficient to eradicate the tumors, whereas tumor regrowth was observed for mice treated with 5 kBq [225Ac]Ac-PSMA-617 and only one out of six mice survived until the end of the study. The enhanced therapeutic efficacy of [225Ac]Ac-SibuDAB as compared to that of [225Ac]Ac-PSMA-617 and reasonable safety data qualify this novel radioligand as a candidate for targeted α-therapy of prostate cancer.

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Section: Resultsmentioning

confidence: 99%

[225Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [225Ac]Ac-PSMA-617

Busslinger

Tschan

Richard³

et al. 2022

Cancers

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“…Studies to date have indicated a low risk of nephrotoxicity with the use of 177 Lu-PSMA-617 for the therapy of hormone-refractory metastatic prostate cancer [45,46]. Nevertheless, nephrotoxicity and tubulointerstitial nephritis are possible side effects, and renal function should be monitored closely during PSMA therapy [47]. As a possible pathogenetic cause, we found PSMA expression in the epithelial cells of the (proximal) tubule system, which is consistent with previous findings in the literature [48].…”

Section: Discussionmentioning

confidence: 99%

PSMA-Expression Is Highly Associated with Histological Subtypes of Renal Cell Carcinoma: Potential Implications for Theranostic Approaches

Bui,

Unterrainer,

Brendel

et al. 2023

Biomedicines

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In renal cell carcinoma (RCC), accurate imaging methods are required for treatment planning and response assessment to therapy. In addition, there is an urgent need for new therapeutic options, especially in metastatic RCC. One way to combine diagnostics and therapy in a so-called theranostic approach is the use of radioligands directed against surface antigens. For instance, radioligands against prostate-specific membrane antigen (PSMA) have already been successfully used for diagnosis and radionuclide therapy of metastatic prostate cancer. Recent studies have demonstrated that PSMA is expressed not only in prostate cancer but also in the neovasculature of several solid tumors, which has raised hopes to use PSMA-guided theranostic approaches in other tumor entities, too. However, data on PSMA expression in different histopathological subtypes of RCC are sparse. Because a better understanding of PSMA expression in RCC is critical to assess which patients would benefit most from theranostic approaches using PSMA-targeted ligands, we investigated the expression pattern of PSMA in different subtypes of RCC on protein level. Immunohistochemical staining for PSMA was performed on formalin-fixed, paraffin-embedded archival material of major different histological subtypes of RCC (clear cell RCC (ccRCC)), papillary RCC (pRCC) and chromophobe RCC (cpRCC). The extent and intensity of PSMA staining were scored semi-quantitatively and correlated with the histological RCC subtypes. Group comparisons were calculated with the Kruskal–Wallis test. In all cases, immunoreactivity was detected only in the tumor-associated vessels and not in tumor cells. Staining intensity was the strongest in ccRCC, followed by cpRCC and pRCC. ccRCC showed the most diffuse staining pattern, followed by cpRCC and pRCC. Our results provide a rationale for PSMA-targeted theranostic approaches in ccRCC and cpRCC.

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“…The most prevalent adverse effect of 225 Ac-PSMA-617 was dry mouth ( 72 – 74 , 76 – 78 ), and when administered in conjunction with 177 Lu-PSMA-617, it may lead to a substantial rise in salivary toxicity. Delayed nephrotoxicity has also been documented following 2 cycles of 225 Ac-PSMA-617 RLT ( 79 ).…”

Section: Radionuclide Label Psma-ligand Used For Therapymentioning

confidence: 99%

Advancements in PSMA ligand radiolabeling for diagnosis and treatment of prostate cancer: a systematic review

Yan,

Zhuo,

et al. 2024

Front. Oncol.

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Prostate cancer(PCa), a leading global health concern, profoundly impacts millions of men worldwide. Progressing through two stages, it initially develops within the prostate and subsequently extends to vital organs such as lymph nodes, bones, lungs, and the liver. In the early phases, castration therapy is often employed to mitigate androgen effects. However, when prostate cancer becomes resistant to this treatment, alternative strategies become imperative. As diagnostic and treatment methodologies for prostate cancer continually advance, radioligand therapy (RLT) has emerged as a promising avenue, yielding noteworthy outcomes. The fundamental principle of RLT involves delivering radionuclide drugs to cancerous lesions through specific carriers or technologies. Subsequently, these radionuclide drugs release radioactive energy, facilitating the destruction of cancer cell tissues. At present, the positron emission tomography (PET) targeting PSMA has been widely developed for the use of diagnosis and staging of PCa. Notably, FDA-approved prostate-specific membrane antigen (PSMA) targeting agents, such as 68Ga-PSMA-11 and 177Lu-PSMA-617, represent significant milestones in enhancing diagnostic precision and therapeutic efficacy. This review emphasizes the current research status and outcomes of various radionuclide-labeled PSMA ligands. The objective is to provide valuable insights for the continued advancement of diagnostic and therapeutic approaches in the realm of prostate cancer.

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Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy

Cited by 8 publications

References 8 publications

[225Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [225Ac]Ac-PSMA-617

[225Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [225Ac]Ac-PSMA-617

PSMA-Expression Is Highly Associated with Histological Subtypes of Renal Cell Carcinoma: Potential Implications for Theranostic Approaches

Advancements in PSMA ligand radiolabeling for diagnosis and treatment of prostate cancer: a systematic review

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