Evidence map›Paper›PMID 39743616›Full record

ArticleEuropean journal of nuclear medicine and molecular imaging2025

JHU-2545 preferentially shields salivary glands and kidneys during PSMA-targeted imaging.

Michael T Nedelcovych, Ranjeet P Dash, Ying Wu, Eun Yong Choi, Rena S Lapidus, Pavel Majer, Andrej Jančařík, Diane Abou, Marie-France Penet, Anastasia Nikolopoulou and 6 more

Abstract read
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In one paragraph

Article in European journal of nuclear medicine and molecular imaging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Dosimetry ofMolecules (Basel, Switzerland) · 2019
    Trial
  2. Article
  3. Review
  4. Article
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  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Michael T NedelcovychJohns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. mtnede@gmail.com.
Ranjeet P DashJohns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
Ying WuJohns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
Eun Yong ChoiTranslational Laboratory Shared Service, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD, 21201, USA.
Rena S LapidusTranslational Laboratory Shared Service, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD, 21201, USA.
Pavel MajerInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i, Prague, 166 10, Czech Republic.
Andrej JančaříkInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic v.v.i, Prague, 166 10, Czech Republic.
Diane AbouDepatment of Radiology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Marie-France PenetDepartments of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
Anastasia NikolopoulouDivision of Radiopharmaceutical Sciences and MI(3), Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
Alex Amor-CoarasaDivision of Radiopharmaceutical Sciences and MI(3), Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
John BabichDivision of Radiopharmaceutical Sciences and MI(3), Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
Daniel L ThorekDepatment of Radiology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
Rana RaisJohns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
Clemens KratochwilDepartment of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
Barbara S SlusherJohns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. bslusher@jhmi.edu.

Funding

The Radium-223 Combination Therapy Space; Improving Response and Clarifying ToxicitiesR01CA240711 · NCI · WASHINGTON UNIVERSITY · PI MICHALSKI, JEFF M., THOREK, DANIEL LYNDON JAFFE · 2020 to 2024
$2.2M
Opening the Therapeutic Window for PSMA-Targeted Molecular RadiotherapyR01CA229893 · NCI · WASHINGTON UNIVERSITY · PI THOREK, DANIEL LYNDON JAFFE · 2019 to 2024
$1.9M
GCPII Inihibitors for the treatment of chemotherapy-induced neuropathyR01CA161056 · NCI · JOHNS HOPKINS UNIVERSITY · PI SLUSHER, BARBARA STAUCH · 2012 to 2016
$1.8M
Kallikrein-Targeted Alpha-Particle Therapy of Late-Stage Prostate CancerR01CA201035 · NCI · WASHINGTON UNIVERSITY · PI THOREK, DANIEL LYNDON JAFFE · 2017 to 2020
$1.4M
IOCB RVO 61388963Maryland TEDCO MII awardNational Institute for Cancer Research Programme EXCELES, ID Project No. LX22NPO5102NCI NIH HHS R01 CA161056NCI NIH HHS R01CA161056NCI NIH HHS R01 CA201035NCI NIH HHS R01CA201035NCI NIH HHS R01 CA229893NCI NIH HHS R01CA229893NCI NIH HHS R01 CA240711NCI NIH HHS R01CA240711
6 · The paper itself

Abstract

purposeProstate-specific membrane antigen (PSMA) radioligand therapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC). Several beta or alpha particle-emitting radionuclide-conjugated small molecules have shown efficacy in late-stage mCRPC and one, [[177Lu]Lu]Lu-PSMA-617, is FDA approved. In addition to tumor upregulation, PSMA is also expressed in kidneys and salivary glands where specific uptake can cause dose-limiting xerostomia and potential for nephrotoxicity. The PSMA inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) can prevent kidney uptake in mice, but also blocks tumor uptake, precluding its clinical utility. Preferential delivery of 2-PMPA to non-malignant tissues could improve the therapeutic window of PSMA radioligand therapy.

methodsA tris(isopropoxycarbonyloxymethyl) (TrisPOC) prodrug of 2-PMPA, JHU-2545, was synthesized to enhance 2-PMPA delivery to non-malignant tissues. Mouse pharmacokinetic experiments were conducted to compare JHU-2545-mediated delivery of 2-PMPA to plasma, kidney, salivary glands, and C4-2 prostate tumor xenograft. Imaging studies were conducted in rats and mice to measure uptake of PSMA PET tracers in kidney, salivary glands, and prostate tumor xenografts with and without JHU-2545 pre-treatment.

resultsJHU-2545 resulted in approximately 3- and 53-fold greater exposure of 2-PMPA in rodent salivary glands (18.0 ± 0.97 h*nmol/g) and kidneys (359 ± 4.16 h*nmol/g) versus prostate tumor xenograft (6.79 ± 0.19 h*nmol/g). JHU-2545 also blocked rodent kidneys and salivary glands uptake of the PSMA PET tracers [68Ga]Ga-PSMA-11 and [18 F]F-DCFPyL by up to 85% with little effect on tumor.

conclusionsJHU-2545 pre-treatment may enable greater cumulative administered doses of PSMA radioligand therapy, possibly improving safety and efficacy.

Indexed as

Antigens, SurfaceGlutamate Carboxypeptidase IIKidneyRadiation-Protective AgentsSalivary GlandsAnimalsCell Line, TumorHumansMaleMiceRatsTissue DistributionAntigens, SurfaceFOLH1 protein, humanGlutamate Carboxypeptidase IIRadiation-Protective AgentsKidneysProstate cancerPSMARadioligand therapySalivary glands

Identifiers

PMID39743616
PMCPMC11928385

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.