Related Experiment Video

Updated: Jul 10, 2026

Preparation, Purification, and Characterization of Lanthanide Complexes for Use as Contrast Agents for Magnetic Resonance Imaging
13:21

Preparation, Purification, and Characterization of Lanthanide Complexes for Use as Contrast Agents for Magnetic Resonance Imaging

Published on: July 21, 2011

Electrophilic chelating agents for irreversible binding of metal chelates to engineered antibodies

A J Chmura1, Brian D Schmidt, Donald T Corson

  • 1Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|January 5, 2002
PubMed

Insights

This study introduces a novel pretargeting strategy for cancer detection and therapy using engineered antibodies and metal chelates. This approach aims to improve tumor visualization and reduce background radioactivity in radioimmunotherapy.

Area of Science:

  • Oncology
  • Radiochemistry
  • Biotechnology

Background:

  • Radiolabeled monoclonal antibodies are crucial for cancer detection and treatment.
  • Limitations include low tumor-to-background ratios in imaging and high background radioactivity in therapy.
  • Pretargeting strategies separate tumor targeting from radiolocalization to overcome these issues.

Purpose of the Study:

  • To develop an improved pretargeting system for cancer radioimmunotherapy.
  • To synthesize novel electrophilic chelates for in vivo use.
  • To engineer an antibody for selective and irreversible binding to these chelates.

Main Methods:

  • Synthesis of novel electrophilic chelates.
  • Protein engineering of an antibody for specific metal chelate binding.
  • Evaluation of the pretargeting system in preclinical cancer models.

Main Results:

  • Successful synthesis of electrophilic chelates designed for in vivo application.
  • Development of an engineered antibody with selective and irreversible binding capabilities.
  • Demonstration of improved tumor targeting and reduced background radioactivity in preclinical studies.

Conclusions:

  • The novel pretargeting approach using engineered antibodies and metal chelates offers significant advantages over existing methods.
  • This strategy holds promise for enhancing the efficacy and safety of radioimmunotherapy for cancer.
  • Further development could lead to improved clinical outcomes in cancer diagnosis and treatment.

More Related Videos

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction11:02

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction

Published on: September 14, 2018

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates08:47

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Published on: March 6, 2019

Related Concept Videos

Metal-Ligand Bonds02:51

Metal-Ligand Bonds

The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
Complexation Equilibria: The Chelate Effect01:19

Complexation Equilibria: The Chelate Effect

In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
EDTA: Chemistry and Properties01:22

EDTA: Chemistry and Properties

Polydentate ligands are most widely used in complexometric titrations because they form more stable complexes with the metal ions than mono- or bidentate ligands due to the chelate effect. Examples of polydentate ligands are ethylenediaminetetraacetic acid (EDTA), crown ethers, and cryptands. The most important feature of optimal polydentate ligands is the ability to form 1:1 complexes in a single-step process. Amino carboxylic acid derivatives are frequently used as complexing agents. EDTA is...
EDTA: Auxiliary Complexing Reagents01:26

EDTA: Auxiliary Complexing Reagents

EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...
Masking and Demasking Agents01:19

Masking and Demasking Agents

EDTA titrations may necessitate masking and demasking agents to temporarily protect a particular metal ion in a mixture from the EDTA reaction. These agents facilitate the sequential analysis of the metal ions by forming stable complexes with some—but not all—metal ions during certain steps.
There are many masking agents, such as cyanide, fluoride, triethanolamine, thiourea, and 2,3-bis(sulfanyl)propan-1-ol (formerly 2,3-dimercapto-1-propanol), with the masking agent chosen based on the metal...
Extraction: Advanced Methods00:56

Extraction: Advanced Methods

Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is formed in...