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Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Related Experiment Video

Updated: Sep 20, 2025

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
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Targeted Radionuclide Therapy Using a Lutetium-177 Labeled Human Anti-CD133 Antibody.

Kevin Wyszatko1, Nancy Janzen1, Napoleon Law2

  • 1Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada.

Molecular Imaging and Biology
|May 22, 2025
PubMed
Summary

Targeted radionuclide therapy using lutetium-177 labeled anti-CD133 antibody ([177Lu]Lu-DOTA-RW03) shows promise for treating refractory cancers. This therapy effectively targets cancer stem cells, reducing tumor growth and increasing survival in preclinical models.

Keywords:
CD133Cancer stem cellRadioimmunotherapyTargeted radionuclide therapy

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Area of Science:

  • Nuclear medicine
  • Oncology
  • Immunotherapy

Background:

  • Cancer stem cells (CSCs) are implicated in tumor recurrence and treatment resistance.
  • Targeting CSC-specific markers like CD133 offers a strategy to eliminate these resilient cells.
  • Refractory tumors often harbor a significant CSC population, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To synthesize and evaluate [177Lu]Lu-DOTA-RW03, a novel radioimmunoconjugate targeting CD133 for cancer therapy.
  • To assess the in vitro binding characteristics and in vivo biodistribution and efficacy of [177Lu]Lu-DOTA-RW03 in a CD133-expressing colorectal cancer model.

Main Methods:

  • Conjugation of a fully human anti-CD133 antibody (RW03) with DOTA-NHS and subsequent radiolabeling with Lutetium-177.
  • In vitro binding assays using CD133-expressing HT-29 cells to determine affinity and immunoreactivity.
  • In vivo biodistribution, SPECT imaging, and dose-escalation therapy studies in immunodeficient mice bearing HT-29 xenografts.

Main Results:

  • [177Lu]Lu-DOTA-RW03 was successfully synthesized with high radiochemical purity and yield, exhibiting excellent binding affinity and immunoreactivity.
  • Significant tumor uptake and favorable tumor-to-blood ratios were observed in vivo, with confirmed antigen specificity.
  • Dose-dependent therapeutic efficacy, including reduced tumor growth and increased survival, was demonstrated, alongside evidence of tumor necrosis.

Conclusions:

  • [177Lu]Lu-DOTA-RW03 demonstrates significant potential as an effective targeted radionuclide therapy for CD133-expressing cancers.
  • The findings support further investigation into [177Lu]Lu-DOTA-RW03 for multidosing and combination treatment strategies in refractory tumors.