Global experience with PSMA-based alpha therapy in prostate cancer

Sathekge, Mike; Bruchertseifer, Frank; Vorster, Mariza; Morgenstern, Alfred; Lawal, Ismaheel

doi:10.1007/s00259-021-05434-9

Cited by 39 publications

(47 citation statements)

References 111 publications

(195 reference statements)

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“…The good diagnostic performance of PSMA-targeted tracers and the high tumor expression of PSMA in advanced PCa have facilitated the investigation of radiotherapeutics that target PSMA, such as [ 177 Lu]Lu-PSMA617 and [ 225 Ac]Ac-PSMA617 [ 124 , 125 , 126 ]. However, responses to RT are generally reflective of the heterogeneity of PSMA expression in PCa tumors.…”

Section: Discussionmentioning

confidence: 99%

The Performance of FDA-Approved PET Imaging Agents in the Detection of Prostate Cancer

Zelchan

Orlova

2022

Biomedicines

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Positron emission tomography (PET) incorporated with X-ray computed tomography (PET/CT) or magnetic resonance imaging (PET/MRI) is increasingly being used as a diagnostic tool for prostate cancer (PCa). In this review, we describe and evaluate the clinical performance of some Food and Drug Administration (FDA)-approved agents used for visualizing PCa: [18F]FDG, [11C]choline, [18F]FACBC, [68Ga]Ga-PSMA-11, [18F]DCFPyL, and [18F]-NaF. We carried out a comprehensive literature search based on articles published from 1 January 2010 to 1 March 2022. We selected English language articles associated with the discovery, preclinical study, clinical study, and diagnostic performance of the imaging agents for the evaluation. Prostate-specific membrane antigen (PSMA)-targeted imaging agents demonstrated superior diagnostic performance in both primary and recurrent PCa, compared with [11C]choline and [18F]FACBC, both of which target dividing cells and are used especially in patients with low prostate-specific antigen (PSA) values. When compared to [18F]-NaF (which is suitable for the detection of bone metastases), PSMA-targeted agents were also capable of detecting lesions in the lymph nodes, soft tissues, and bone. However, a limitation of PSMA-targeted imaging was the heterogeneity of PSMA expression in PCa, and consequently, a combination of two PET tracers was proposed to overcome this obstacle. The preliminary studies indicated that the use of PSMA-targeted scanning is more cost efficient than conventional imaging modalities for high-risk PCa patients. Furthering the development of imaging agents that target PCa-associated receptors and molecules could improve PET-based diagnosis of PCa.

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Section: Discussionmentioning

confidence: 99%

The Performance of FDA-Approved PET Imaging Agents in the Detection of Prostate Cancer

Zelchan

Orlova

2022

Biomedicines

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“…When these factors are taken into account, despite that many different alpha-emitting radionuclides have been identified, only a few have desirable characteristics that render them suitable for clinical application ( 66 , 67 ). Of the alpha-emitting radionuclides that have been identified as suitable for therapeutic use, several candidates have now been complexed to ligands such as PSMA inhibitors for evaluation in preclinical and clinical studies for cancer such as mCRPC ( 71 ). Following these early evaluations, four of the most promising isotopes emerging within the ART field are 225 Ac, 211 At, 212 Pb, and thorium-227 ( 227 Th)–although 213 Bi has been used with positive results in select malignancies, we are not aware of large scale commercial efforts with this isotope.…”

Section: Section 3: the Future Is Alphamentioning

confidence: 99%

Commercial and business aspects of alpha radioligand therapeutics

Ostuni¹,

Taylor²

2023

Front. Med.

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Radioligand therapy (RLT) is gaining traction as a safe and effective targeted approach for the treatment of many cancer types, reflected by a substantial and growing commercial market (valued at $7.78 billion in 2021, with a projected value of $13.07 billion by 2030). Beta-emitting RLTs have a long history of clinical success dating back to the approval of Zevalin and Bexxar in the early 2000s, later followed by Lutathera and Pluvicto. Alpha radioligand therapeutics (ARTs) offer the potential for even greater success. Driven by ground-breaking clinical results in early trials, improved isotope availability, and better understanding of isotope and disease characteristics, the global market for alpha emitters was estimated at $672.3 million for the year 2020, with projected growth to $5.2 billion by 2027. New company formations, promising clinical trial data, and progression for many radioligand therapy products, as well as an inflow of investor capital, are contributing to this expanding field. Future growth will be fueled by further efficacy and safety data from ART clinical trials and real-world results, but challenges remain. Radionuclide supply, manufacturing, and distribution are key obstacles for growth of the field. New models of delivery are needed, along with cross-disciplinary training of specialized practitioners, to ensure patient access and avoid challenges faced by early RLT candidates such as Zevalin and Bexxar. Understanding of the history of radiation medicine is critical to inform what may be important to the success of ART–most past projections were inaccurate and it is important to analyze the reasons for this. Practical considerations in how radiation medicine is delivered and administered are important to understand in order to inform future approaches.

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“…Three meta-analyses have been reported using 225 Ac-PSMA-617 (41)(42)(43) and recent reviews with 225 Ac-PSMA-617 have been presented as well (44). Thus, an exhaustive review of the literature is not warranted here.…”

Section: Prostate Specific Membrane Antigen Targeted Alpha Particles ...mentioning

confidence: 99%

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts

Sartor

Baghian

2022

Front. Med.

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Prostate specific membrane antigen (PSMA) represents a validated target for prostate cancer therapeutics. The phase III VISION study with 177lutetium (177Lu)-PSMA-617 represented a pivotal step forward and the FDA has now approved this agent in advanced metastatic castrate-resistant prostate cancer (mCRPC). A number of other PSMA targeted radiopharmaceuticals are now under development. Some of these agents are targeted to PSMA via monoclonal antibodies such as J591 and TLX591. Others are targeted to PSMA via small molecules such as PSMA-617, PSMA I&T, MIP-1095, etc. In addition to the use of various ligands, multiple isotopes are now in clinical trials. Beta emitters in development include 177Lu, 131iodide (131I), and 67copper (67Cu). Targeted alpha emitters potentially include 225actinium (225Ac), 227thorium (227Th), and 212lead (212Pb). Phase III trials are underway with both 177Lu-PSMA-617 and 177Lu-PSMA I&T in mCRPC. Single dose phase I trials are complete with 225Ac-J591 but additional data are need to launch a phase III. Data are promising with 225Ac-PSMA-617 but concerns remain over salivary and renal toxicity. Tandem therapies are also considered combining both beta and alpha-targeted therapy. Taken together the field of PSMA targeted radiopharmaceuticals is rapidly developing. The targeted alpha therapies are particularly promising and several developmental paths forward are being considered in the near future.

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Global experience with PSMA-based alpha therapy in prostate cancer

Cited by 39 publications

References 111 publications

The Performance of FDA-Approved PET Imaging Agents in the Detection of Prostate Cancer

The Performance of FDA-Approved PET Imaging Agents in the Detection of Prostate Cancer

Commercial and business aspects of alpha radioligand therapeutics

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts

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