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Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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 specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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 specific...

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Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
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B7-H4-targeted radiotheranostics enable precise imaging and potent therapy across solid tumor models.

Behnaz Ghaemi1, Colleen P Olkowski1, Falguni Basuli2

  • 1Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Science Advances
|July 1, 2026
PubMed
Summary

This study introduces a novel B7-H4-directed radiotheranostic antibody for cancer imaging and therapy. The B7-H4 antibody successfully visualized tumors and demonstrated potent, safe antitumor effects in preclinical models.

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Area of Science:

  • Oncology
  • Radiochemistry
  • Immunotherapy

Background:

  • B7-H4 is an immune checkpoint protein overexpressed in many solid tumors.
  • Its limited expression in normal tissues makes it an ideal target for cancer therapy and imaging.

Purpose of the Study:

  • To develop and evaluate a B7-H4-targeted radiotheranostic antibody for PET imaging and radionuclide therapy.
  • To assess the efficacy and safety of this targeted approach in preclinical models.

Main Methods:

  • Development of a B7-H4 antibody conjugated with Zirconium-89 ([89Zr]) for PET imaging.
  • Conjugation of the antibody with Lutetium-177 ([177Lu]) or Actinium-225 ([225Ac]) for beta or alpha particle therapy.
  • Evaluation of imaging capabilities and therapeutic efficacy in B7-H4 expressing xenografts.

Main Results:

  • [89Zr]-immunoPET provided quantitative, whole-body visualization of B7-H4 expression, differentiating tumor burdens.
  • Therapy with [177Lu]- or [225Ac]-conjugated antibody showed significant, antigen-dependent tumor regression, including complete and durable responses.
  • Therapeutic constructs were well-tolerated, with only transient myelosuppression and no significant organ toxicity.

Conclusions:

  • B7-H4 is a promising target for integrated imaging and radionuclide therapy.
  • The developed B7-H4-directed radiotheranostic antibody offers a potential new strategy for cancer treatment.