Evidence map›Paper›PMID 38832336›Full record

ArticleInternational journal of nanomedicine2024

Multimodal, PSMA-Targeted, PAMAM Dendrimer-Drug Conjugates for Treatment of Prostate Cancer: Preclinical Evaluation.

Wojciech G Lesniak, Srikanth Boinapally, Gabriela Lofland, Zirui Jiang, Catherine A Foss, Babak Behman Azad, Anna Jablonska, Mauro A Garcia, Maria Brzezinski, Martin G Pomper

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of nanomedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
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

10 authors.

Wojciech G LesniakRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.ORCID 0000-0003-0734-4685
Srikanth BoinapallyRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.
Gabriela LoflandRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.
Zirui JiangRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.
Catherine A FossRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.
Babak Behman AzadRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.
Anna JablonskaRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.
Mauro A GarciaRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.
Maria BrzezinskiRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.
Martin G PomperRussell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 21287, USA.

Funding

Training/Dissemination-Resource for Molecular Imaging Agents in Precision MedicineP41EB024495 · NIBIB · UT SOUTHWESTERN MEDICAL CENTER · PI MARTIN G POMPER · 2017 to 2026
$11.8M
PSMA-based Cancer Imaging AgentsR01CA134675 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI POMPER, MARTIN G · 2009 to 2025
$6.2M
Small Molecule PSMA-Targeted Alpha TherapyR01CA184228 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI POMPER, MARTIN G, ZALUTSKY, MICHAEL ROD · 2014 to 2023
$3.6M
Pharmacology and Molecular Sciences Training Program: Enhancing Inclusivity Through Universal Design for Learning in Graduate CoursesT32GM135083 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Caren L. Freel Meyers · 2020 to 2026
$3.3M
PSMA Directed Imaging of Prostate Cancer Focus on Androgen Receptor DynamicsU01CA183031 · NCI · JOHNS HOPKINS UNIVERSITY · PI DEWEESE, THEODORE L, POMPER, MARTIN G · 2015 to 2017
$1.2M
NCI NIH HHS R01 CA134675NCI NIH HHS R01 CA184228NCI NIH HHS U01 CA183031NIBIB NIH HHS P41 EB024495NIGMS NIH HHS T32 GM135083
6 · The paper itself

Abstract

Introduction: Prostate cancer (PC) is the second most common cancer and the fifth most frequent cause of cancer death among men. Prostate-specific membrane antigen (PSMA) expression is associated with aggressive PC, with expression in over 90% of patients with metastatic disease. Those characteristics have led to its use for PC diagnosis and therapies with radiopharmaceuticals, antibody-drug conjugates, and nanoparticles. Despite these advancements, none of the current therapeutics are curative and show some degree of toxicity. Here we present the synthesis and preclinical evaluation of a multimodal, PSMA-targeted dendrimer-drug conjugate (PT-DDC), synthesized using poly(amidoamine) (PAMAM) dendrimers. PT-DDC was designed to enable imaging of drug delivery, providing valuable insights to understand and enhance therapeutic response. Methods: The PT-DDC was synthesized through consecutive conjugation of generation-4 PAMAM dendrimers with maytansinoid-1 (DM1) a highly potent antimitotic agent, Cy5 infrared dye for optical imaging, 2,2',2"-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) chelator for radiolabeling with copper-64 and positron emission tomography tomography/computed tomography (PET/CT), lysine-urea-glutamate (KEU) PSMA-targeting moiety and the remaining terminal primary amines were capped with butane-1,2-diol. Non-targeted control dendrimer-drug conjugate (Ctrl-DDC) was formulated without conjugation of KEU. PT-DDC and Ctrl-DDC were characterized using high-performance liquid chromatography, matrix assisted laser desorption ionization mass spectrometry and dynamic light scattering. In vitro and in vivo evaluation of PT-DDC and Ctrl-DDC were carried out in isogenic human prostate cancer PSMA Results: PT-DDC was stable in 1×PBS and human blood plasma and required glutathione for DM1 release. Optical, PET/CT and biodistribution studies confirmed the in vivo PSMA-specificity of PT-DDC. PT-DDC demonstrated dose-dependent accumulation and cytotoxicity in PSMA Conclusion: In this study, we synthesized a multimodal theranostic agent capable of delivering DM1 and a radionuclide to PSMA

Indexed as

Antigens, SurfaceDendrimersGlutamate Carboxypeptidase IIProstatic NeoplasmsAnimalsCell Line, TumorDrug Delivery SystemsHumansMaleMicePositron Emission Tomography Computed TomographyAntigens, SurfaceDendrimersFOLH1 protein, humanGlutamate Carboxypeptidase IIPAMAM StarburstPAMAM dendrimerprostate cancerPSMAtargeted cancer treatmenttheranostics

Identifiers

PMID38832336
PMCPMC11146619

What OpenQuestion holds

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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.