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

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

Published on: March 6, 2019

Site-specific bioconjugation and nuclear imaging.

Joni Sebastiano¹, Zachary V Samuels², Wei-Siang Kao³

¹Department of Chemistry, Hunter College, City University of New York, New York, NY, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Ph.D. Program in Biochemistry, Graduate Center of City University of New York, New York, NY, USA.

Current Opinion in Chemical Biology

|June 4, 2024

Summary

This summary is machine-generated.

Site-specific bioconjugation creates better-defined radioimmunoconjugates for nuclear imaging. These advanced methods improve in vivo performance over traditional random labeling for positron emission tomography (PET) and single-photon emission computed tomography (SPECT).

Keywords:

Antibody Antibody fragment Click chemistry Heavy chain glycans Molecular imaging Monoclonal antibody Positron emission tomography Single photon emission computed tomography Site-selective bioconjugation Site-specific bioconjugation Unnatural amino acids

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Area of Science:

Bioconjugation Chemistry
Nuclear Medicine
Molecular Imaging

Background:

Monoclonal antibodies are effective vectors for delivering radionuclides in PET and SPECT imaging.
Traditional stochastic radiolabeling methods yield heterogeneous probes that can impair target binding.
There is a need for improved methods to create well-defined radioimmunoconjugates.

Purpose of the Study:

To review recent advances in site-specific and site-selective bioconjugation strategies for radiolabeling antibodies.
To highlight the development and clinical translation of novel nuclear imaging agents.
To compare the performance of site-specifically modified probes with randomly modified ones.

Main Methods:

Development of site-specific and site-selective bioconjugation techniques.
Targeting heavy chain glycans, peptide tags, and unnatural amino acids for radiolabeling.
Evaluation of radioimmunoconjugate homogeneity and in vivo performance.

Main Results:

Innovative bioconjugation strategies yield better-defined and more homogeneous radioimmunoconjugates.
Site-specific methods overcome limitations of stochastic labeling, improving antibody function.
Several novel nuclear imaging agents have been developed and some are in clinical translation.

Conclusions:

Site-specific bioconjugation represents a significant advancement in creating radioimmunoconjugates for nuclear imaging.
These improved probes offer superior in vivo performance compared to traditional methods.
Targeting specific sites like glycans, tags, and unnatural amino acids is key to developing next-generation nuclear imaging agents.