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Related Concept Videos

Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...

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Related Experiment Video

Updated: Jul 16, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Development of Radioligand Therapy-Responsive Syngeneic Prostate Models through Murine Prostate-Specific Membrane

Mathis Richard1,2, Beatrice Louis1,2, Marco F Taddio1,2

  • 1Ahmanson Translational Theranostic Division, David Geffen School of Medicine, University of California-Los Angeles, 90095 Los Angeles, California, United States.

ACS Pharmacology & Translational Science
|July 15, 2026
PubMed
Summary

Developing immunocompetent murine models for prostate cancer theranostics is challenging. Researchers found that murine PSMA (mPSMA) has lower radiotracer uptake than human PSMA (hPSMA), limiting therapeutic efficacy in preclinical models.

Keywords:
pharmacodynamicspoint mutationprostate-specific membrane antigen (PSMA)protein−ligand interactionsradioligand therapysyngeneic prostate cancer model

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07:01

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Published on: August 29, 2016

Area of Science:

  • Oncology
  • Preclinical Research
  • Theranostics

Background:

  • Developing immunocompetent murine models is crucial for metastatic castration-resistant prostate cancer (mCRPC) theranostic research.
  • Transfecting murine cells with human prostate-specific membrane antigen (PSMA) leads to immune rejection, necessitating alternative strategies.

Purpose of the Study:

  • To evaluate radiotracer efficacy in immunocompetent murine models expressing murine PSMA (mPSMA).
  • To assess the therapeutic response of radioligand therapy (RLT) using PSMA-617 in these models.

Main Methods:

  • Engineered murine cell lines to express mPSMA.
  • Administered [68Ga]-Ga-PSMA-11 for imaging and PSMA-617 for radioligand therapy.
  • Analyzed differences in PSMA internalization, binding, and structural features between murine and human PSMA.
  • Introduced a single amino acid substitution in mPSMA to restore internalization motifs.

Main Results:

  • Imaging with [68Ga]-Ga-PSMA-11 was satisfactory, but PSMA-617 RLT showed no therapeutic response.
  • mPSMA exhibited significantly lower radiotracer internalization and binding compared to human PSMA (hPSMA), especially with PSMA-617.
  • A single amino acid substitution restored mPSMA internalization to hPSMA levels, yet therapeutic efficacy remained absent.
  • Species-specific structural differences in the PSMA binding pocket, like Ser550 steric hindrance, may limit ligand positioning.

Conclusions:

  • There are significant differences between murine and human PSMA, and between PSMA-11 and PSMA-617 ligands, impacting theranostic efficacy.
  • The lack of equivalence between imaging and therapeutic ligands complicates preclinical model development.
  • Developing translationally relevant murine models requires consideration of both receptor trafficking and PSMA binding pocket structural features.