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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...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...

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Related Experiment Video

Updated: Jul 17, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

FcRn-Targeted Alpha Therapy Using [225Ac]Ac-Macropa-Rozanolixizumab Enables Potent Antitumor Activity.

Saba Shirin1, Syed Qaiser Shah2, Ralph Santos-Oliveira3

  • 1Nuclear Medicine Research Laboratory, Institute of Chemical Sciences, University of Peshawar, Peshawar, KP, 25120, Pakistan.

Molecular Imaging and Biology
|July 15, 2026
PubMed
Summary

A novel alpha-radioimmunotherapy targeting the neonatal Fc receptor (FcRn) demonstrated significant survival benefits in preclinical cancer models. This targeted approach shows promise for future cancer treatments by delivering cytotoxic alpha particles specifically to tumors.

Keywords:
Actinum-225DosimetryFcRn receptorMacropa amide chelatorTargeted alpha therapy

Related Experiment Videos

Last Updated: Jul 17, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Area of Science:

  • Nuclear Medicine
  • Oncology
  • Immunotherapy

Background:

  • The neonatal Fc receptor (FcRn) is overexpressed in various cancers, making it a potential therapeutic target.
  • Targeting FcRn with monoclonal antibodies offers a promising strategy, but careful toxicity assessment is crucial due to its presence in healthy tissues.

Purpose of the Study:

  • To report the preclinical development and evaluation of [225Ac]Ac-Macropa-rozanolixizumab, an alpha-radioimmunotherapeutic agent targeting FcRn.
  • To assess the efficacy and biodistribution of this novel agent in a xenograft cancer model.

Main Methods:

  • Rozanolixizumab was conjugated with Macropa using a site-specific approach and a PEG4 linker, then radiolabeled with Actinium-225 (225Ac) under mild aqueous conditions.
  • In vitro assays evaluated FcRn binding, immunoreactivity, and cytotoxicity.
  • In vivo studies in mice bearing FcRn-positive xenografts assessed biodistribution, dosimetry, and antitumor activity following a single dose.

Main Results:

  • The conjugation and radiolabeling yielded a homogeneous product with retained FcRn binding, albeit with reduced affinity compared to native rozanolixizumab.
  • The radioimmunoconjugate exhibited potent FcRn-dependent cytotoxicity in vitro and significant antitumor activity in vivo, leading to improved survival.
  • Biodistribution studies showed preferential tumor uptake with favorable dosimetry, indicated by a high tumor-to-bone marrow absorbed dose ratio (17.2).

Conclusions:

  • [225Ac]Ac-Macropa-rozanolixizumab demonstrated FcRn-specific alpha-particle cytotoxicity and favorable dosimetric properties in a preclinical xenograft model.
  • These findings support the FcRn as a viable target for radioimmunotherapy.
  • Further investigations are warranted to evaluate toxicity, endogenous IgG competition, and translational applicability.