A simple strategy to reduce the salivary gland and kidney uptake of PSMA-targeting small molecule radiopharmaceuticals

Kalidindi, Teja; Lee, Sang Kyu; Jou, Katerina; Chakraborty, Goutam; Skafida, Myrto; Tagawa, Scott T.; Bander, Neil H.; Schöder, Heiko; Bodei, Lisa; Pandit‐Taskar, Neeta; Lewis, Jason S.; Larson, Steven M.; Osborne, Joseph R.; Pillarsetty, Naga Vara Kishore

doi:10.1007/s00259-020-05150-w

Cited by 30 publications

(32 citation statements)

References 39 publications

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“…The effectiveness of this intervention is still under debate [97,98]. Competitive inhibition for binding at PSMA receptor expressed in normal organs has been attempted with cold PSMA or PSMA congeners such as monosodium glutamate as another way to reduce off-target PSMA radioligand uptake in the salivary glands [99][100][101][102][103]. While this competitive inhibition may successfully reduce off-target PSMA radioligand in normal organs such as the salivary gland, a reduction in tumor uptake is possible [102].…”

Section: Toxicitymentioning

confidence: 99%

Global experience with PSMA-based alpha therapy in prostate cancer

Sathekge

Bruchertseifer

Vorster

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose This review discusses the current state of prostate-specific membrane antigen (PSMA)-based alpha therapy of metastatic castration-resistant prostate cancer (mCRPC). With this in-depth discussion on the growing field of PSMA-based alpha therapy (PAT), we aimed to increase the interactions between basic scientists and physician–scientists in order to advance the field. Methods To achieve this, we discuss the potential, current status, and opportunities for alpha therapy and strategies, attempted to date, and important questions that need to be addressed. The paper reviews important concepts, including whom to treat, how to treat, what to expect regarding treatment outcome, and toxicity, and areas requiring further investigations. Results There is much excitement about the potential of this field. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other conventional therapies. Conclusion A better understanding of the strengths and limitations of PAT may help in creating an effective therapy for mCRPC and design a rational combinatorial approach to treatment by targeting different tumor pathways.

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Section: Toxicitymentioning

confidence: 99%

Global experience with PSMA-based alpha therapy in prostate cancer

Sathekge

Bruchertseifer

Vorster

et al. 2021

Eur J Nucl Med Mol Imaging

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“…In the meantime, the accessibility of the whole conjugate should not be obstructed to the active site through the funnel (~20Å) in PSMA (Figure 1) [64]. 177 Lu]Lu-PSMA-617 is more tuned for radionuclide therapy with slower in vivo kinetics to enhance tumor uptake and lower renal accumulation to reduce the kidney toxicity [65,66]. Given the structures of the agents, the current efforts are focused on chemical modifications of the linker between the chelator and the PSMA-target moiety without compromising the PSMA-specific binding affinity.…”

Section: Current Status Of Psma-targeting Agentsmentioning

confidence: 99%

PSMA-Targeting Imaging and Theranostic Agents—Current Status and Future Perspective

Debnath

Zhou

McLaughlin

et al. 2022

IJMS

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In the past two decades, extensive efforts have been made to develop agents targeting prostate-specific membrane antigen (PSMA) for prostate cancer imaging and therapy. To date, represented by two recent approvals of [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL by the United States Food and Drug Administration (US-FDA) for positron emission tomography (PET) imaging to identify suspected metastases or recurrence in patients with prostate cancer, PSMA-targeting imaging and theranostic agents derived from small molecule PSMA inhibitors have advanced to clinical practice and trials of prostate cancer. The focus of current development of new PSMA-targeting agents has thus shifted to the improvement of in vivo pharmacokinetics and higher specific binding affinity with the aims to further increase the detection sensitivity and specificity and minimize the toxicity to non-target tissues, particularly the kidneys. The main strategies involve systematic chemical modifications of the linkage between the targeting moiety and imaging/therapy payloads. In addition to a summary of the development history of PSMA-targeting agents, this review provides an overview of current advances and future promise of PSMA-targeted imaging and theranostics with focuses on the structural determinants of the chemical modification towards the next generation of PSMA-targeting agents.

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“…A few interventions have been attempted with limited success. These include external cooling with ice packs applied over the salivary glands (parotids and submandibular), injection of Botulin toxin, the co-administration of monosodium glutamate as well as saline irrigation and steroid injections [123][124][125][126]. Considering the tumour sink effect, the de-escalation method first described and implemented by Sathekge and colleagues is one intervention that seems to have success.…”

Section: Toxicitymentioning

confidence: 99%

PSMA Theranostics: Science and Practice

Mokoala

Lawal

Lengana³

et al. 2021

Cancers

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Prostate cancer (PCa) causes significant morbidity and mortality in men globally. While localized PCa may be managed with curative intent by surgery and/or radiation therapy, the management of advanced hormone resistant metastatic disease (mCRPC) is more challenging. Theranostics is a principle based on the ability to use an organ specific ligand and label it to both a diagnostic and a therapeutic agent. The overexpression of prostate specific membrane antigen (PSMA) on prostate cancer cells creates a unique opportunity for development of targeted radionuclide therapy. The use of both beta and alpha emitting particles has shown great success. Several clinical trials have been initiated assessing the efficacy and safety profile of these radionuclide agents. The results are encouraging with PSMA directed radioligand therapy performing well in patients who have exhausted all other standard treatment options. Future studies need to assess the timing of introduction of these radionuclide therapies in the management schema of mCRPC. Drugs or therapies are not without side effects and targeted radionuclide therapies presents a new set of toxicities including xerostomia and myelosuppression. New therapeutic strategies are being explored to improve outcomes while keeping toxicities to a minimum. This review aims to look at the various PSMA labelled tracers that form part of the theragnostic approach and subsequently delve into the progress made in the area of radionuclide therapy.

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A simple strategy to reduce the salivary gland and kidney uptake of PSMA-targeting small molecule radiopharmaceuticals

Cited by 30 publications

References 39 publications

Global experience with PSMA-based alpha therapy in prostate cancer

Global experience with PSMA-based alpha therapy in prostate cancer

PSMA-Targeting Imaging and Theranostic Agents—Current Status and Future Perspective

PSMA Theranostics: Science and Practice

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