ArticleEuropean journal of nuclear medicine and molecular imaging2023
Cross-reactivity to glutamate carboxypeptidase III causes undesired salivary gland and kidney uptake of PSMA-targeted small-molecule radionuclide therapeutics.
Article in European journal of nuclear medicine and molecular imaging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 39 citations in OpenAlex.
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- JHU-2545 preferentially shields salivary glands and kidneys during PSMA-targeted imaging.European journal of nuclear medicine and molecular imaging · 2025Article
- Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer.Nature reviews. Urology · 2025Review
- The Blood-prostate Barrier: An Obstacle to Drug Delivery into the Prostate.Current drug delivery · 2025Review
- FDA-approved drugs featuring macrocycles or medium-sized rings.Archiv der Pharmazie · 2025Review
- Targeted interleukin-2 enhances the in vivo anti-cancer activity of Pluvicto™.European journal of nuclear medicine and molecular imaging · 2024Article
- Salivary toxicity from PSMA-targeted radiopharmaceuticals: What we have learned and where we are going.Cancer treatment reviews · 2024Review
- Hematological and renal toxicity in mice after three cycles of high activity [Scientific reports · 2024Article
- DNA-encoded chemical libraries enable the discovery of potent PSMA-ligands with substantially reduced affinity towards the GCPIII anti-target.Chemical science · 2024Article
- Human ABC and SLC Transporters: The Culprit Responsible for Unspecific PSMA-617 Uptake?Pharmaceuticals (Basel, Switzerland) · 2024Article
- A novel PSMA-targeting tracer with highly negatively charged linker demonstrates decreased salivary gland uptake in mice compared to [EJNMMI radiopharmacy and chemistry · 2024Article
- Alpha Particle-Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery.Molecular imaging and biology · 2023Review
- Targeting Prostate Cancer Using Bispecific T-Cell Engagers against Prostate-Specific Membrane Antigen.ACS pharmacology & translational science · 2023Article
- A DNA-encoded chemical library based on chiral 4-amino-proline enables stereospecific isozyme-selective protein recognition.Nature chemistry · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeRecently, Pluvicto™ ([
methodsWe compared the sequence of PSMA with the entire human proteome to identify proteins closely related to the target. We have identified glutamate carboxypeptidase III (GCPIII), N-acetylated alpha-linked acidic dipeptidase like 1 (NAALADL-1), and transferrin receptor 1 (TfR1) as extracellular targets with the highest similarity to PSMA. The affinity of compound 1 for PSMA, GCPIII, NAALADL-1, and TfR1 was measured by fluorescence polarization. The expression of the putative anti-target GCPIII was assessed by immunofluorescence on human salivary glands and kidney, using commercially available antibodies.
resultsA fluorescent derivative of Pluvicto™ (compound 1) bound tightly to PSMA and to GCPIII in fluorescence polarization experiments, while no interaction was observed with NAALADL-1 and TfR1. Immunofluorescence analysis revealed abundant expression of GCPIII both in healthy human kidney and salivary glands.
conclusionWe conclude that the membranous expression of GCPIII in kidney and salivary gland may be the underlying cause for unwanted accumulation of Pluvicto™ and other Glu-ureido PSMA radio pharmaceuticals in patients.
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