Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer: a systematic review

Patell, Kanchi; Kurian, Matthew; García, Jorge A.; Mendiratta, Prateek; Barata, Pedro C.; Jia, Angela Y.; Spratt, Daniel E.; Brown, Jason

doi:10.1080/14737140.2023.2213892

Cited by 16 publications

(11 citation statements)

References 92 publications

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“…The success of 177 Lu-based radioligand therapy and peptide receptor radionuclide therapy has contributed to the growing popularity of 177 Lu as a radioisotope for radioimmunotherapy [20]. 177 Lu-PSMA has shown promising results as a treatment option for metastatic castration-resistant prostate cancer following chemotherapy and hormonal therapy [21]. 177 Lu-[DOTA0,Tyr3]-octreotate effectively reduces tumor growth and stabilizes disease in patients with gastroenteropancreatic well-differentiated neuroendocrine tumors, leading to its establishment as a second-or third-line treatment option [22].…”

Section: Discussionmentioning

confidence: 99%

<sup>177</sup>Lu Anti-angiogenic Radioimmunotherapy Targeting ATP synthase in Gastric Cancer Model

Park,

An,

Kim

et al. 2024

Preprint

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This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate syn-thase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in se-rum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, 177Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. 177Lu-DOTA-ATPS mAb treatment sig-nificantly reduced the viability of MKN-45 cells in a dose-dependent manner. In a xenograft tumor model, this radioimmunotherapy strategy led to substantial tumor growth inhibition (82.8%). Furthermore, combining 177Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, en-hanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed 177Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This ap-proach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.

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Section: Discussionmentioning

confidence: 99%

<sup>177</sup>Lu Anti-angiogenic Radioimmunotherapy Targeting ATP synthase in Gastric Cancer Model

Park,

An,

Kim

et al. 2024

Preprint

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“…It revealed that approximately 2/3 of any decrease in PSA and 1/3 of any decrease in PSA greater than 50% can be expected after the first cycle of [ 177 Lu]Lu-PSMA therapy [ 52 ]. Subsequently, in a recent systematic review conducted by Patell et al, the authors performed a comprehensive qualitative analysis of the existing literature [ 53 ]. The authors determined that [ 177 Lu]Lu-PSMA had shown a minimal toxicity profile and was generally well tolerated in male patients with advanced metastatic disease that is unresponsive to conventional treatments [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, in a recent systematic review conducted by Patell et al, the authors performed a comprehensive qualitative analysis of the existing literature [ 53 ]. The authors determined that [ 177 Lu]Lu-PSMA had shown a minimal toxicity profile and was generally well tolerated in male patients with advanced metastatic disease that is unresponsive to conventional treatments [ 53 ]. Both retrospective analyses and prospective clinical trials have indicated that PSMA RLT is a viable treatment option for individuals with mCRPC who have not responded to traditional hormonal therapies and chemotherapy [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

From Despair to Hope: First Arabic Experience of 177Lu-PSMA and 161Tb-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer

Al-Ibraheem,

Abdlkadir,

Sweedat

et al. 2024

Cancers

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The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [177Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [68Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy’s safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally.

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“…However, the rarity of this cell type in the peripheral blood and the loss of EpCAM expression on CTCs after EMT limits the capacity of EpCAM mAb-based approaches to effectively isolate CTCs [ 47 ]. Herein, we demonstrated that a CTC isolation system that targets mHsp70 on tumor cells [ 27 ] is superior to an EpCAM mAb-based system since at least equal, but mostly higher numbers of CTCs could be isolated from the peripheral blood of patients with metastatic prostate cancer who received a [ 177 Lu]-PSMA-radioligand therapy later on [ 49 ], endometrial carcinoma [ 50 ], lung and squamous cell carcinoma of the head and neck. Moreover, elevated circulating Hsp70 levels in the blood, which are most likely derived from Hsp70 that is actively released in extracellular lipid micro-vesicles from viable tumor cells [ 21 ], do not negatively affect the mHsp70-targeted CTC isolation process.…”

Section: Discussionmentioning

confidence: 99%

Hsp70—A Universal Biomarker for Predicting Therapeutic Failure in Human Female Cancers and a Target for CTC Isolation in Advanced Cancers

Xanthopoulos,

Samt,

Guder

et al. 2023

Biomedicines

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Heat shock protein 70 (Hsp70) is frequently overexpressed in many different tumor types. However, Hsp70 has also been shown to be selectively presented on the plasma membrane of tumor cells, but not normal cells, and this membrane form of Hsp70 (mHsp70) could be considered a universal tumor biomarker. Since viable, mHsp70-positive tumor cells actively release Hsp70 in lipid micro-vesicles, we investigated the utility of Hsp70 in circulation as a universal tumor biomarker and its potential as an early predictive marker of therapeutic failure. We have also evaluated mHsp70 as a target for the isolation and enumeration of circulating tumor cells (CTCs) in patients with different tumor entities. Circulating vesicular Hsp70 levels were measured in the peripheral blood of tumor patients with the compHsp70 ELISA. CTCs were isolated using cmHsp70.1 and EpCAM monoclonal antibody (mAb)-based bead approaches and characterized by immunohistochemistry using cytokeratin and CD45-specific antibodies. In two out of 35 patients exhibiting therapeutic failure two years after initial diagnosis of non-metastatic breast cancer, progressively increasing levels of circulating Hsp70 had already been observed during therapy, whereas levels in patients without subsequent recurrence remained unaltered. With regards to CTC isolation from patients with different tumors, an Hsp70 mAb-based selection system appears superior to an EpCAM mAb-based approach. Extracellular and mHsp70 can therefore serve as a predictive biomarker for therapeutic failure in early-stage tumors and as a target for the isolation of CTCs in various tumor diseases.

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Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer: a systematic review

Cited by 16 publications

References 92 publications

<sup>177</sup>Lu Anti-angiogenic Radioimmunotherapy Targeting ATP synthase in Gastric Cancer Model

<sup>177</sup>Lu Anti-angiogenic Radioimmunotherapy Targeting ATP synthase in Gastric Cancer Model

From Despair to Hope: First Arabic Experience of 177Lu-PSMA and 161Tb-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer

Hsp70—A Universal Biomarker for Predicting Therapeutic Failure in Human Female Cancers and a Target for CTC Isolation in Advanced Cancers

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