Skip to main content
Journal cover image

Site-Specific Radiohalogenation of a HER2-Targeted Single-Domain Antibody Fragment Using a Novel Residualizing Prosthetic Agent.

Publication ,  Journal Article
Feng, Y; Sarrett, SM; Meshaw, RL; Vaidyanathan, G; Cornejo, MA; Zeglis, BM; Zalutsky, MR
Published in: J Med Chem
November 24, 2022

Because of their rapid tumor accumulation and normal tissue clearance, single-domain antibody fragments (sdAbs) are an attractive vehicle for developing radiotherapeutics labeled with the α-emitter 211At. Herein, we have evaluated iso-[211At]AGMB-PODS, a prosthetic agent that combines a functionality for residualizing radiohalogens with a phenyloxadiazolyl methylsulfone (PODS) moiety for site-specific sdAb conjugation. Iso-[211At]AGMB-PODS and its radioiodinated analogue were evaluated for thiol-selective conjugation to anti-HER2 5F7 sdAb bearing a C-terminus GGC tail. Both radiohalogenated PODS-5F7GGC conjugates were synthesized in good radiochemical yields and retained high binding affinity on HER2-positive BT474 breast carcinoma cells. Iso-[211At]AGMB-PODS-5F7GGC was considerably more stable in vitro than its maleimide analogue in the presence of cysteine and human serum albumin (HSA) and exhibited excellent tumor uptake and high in vivo stability. Superior tumor-to-kidney activity ratios were seen for both radiohalogenated PODS-5F7GGC conjugates compared with [177Lu]Lu-DOTA-PODS-5F7GGC. These results suggest that iso-[211At]AGMB-PODS-5F7GGC warrants further evaluation for the treatment of HER2-expressing malignancies.

Duke Scholars

Published In

J Med Chem

DOI

EISSN

1520-4804

Publication Date

November 24, 2022

Volume

65

Issue

22

Start / End Page

15358 / 15373

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Single-Domain Antibodies
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Radiopharmaceuticals
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Female
  • Cell Line, Tumor
  • Breast Neoplasms
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Feng, Y., Sarrett, S. M., Meshaw, R. L., Vaidyanathan, G., Cornejo, M. A., Zeglis, B. M., & Zalutsky, M. R. (2022). Site-Specific Radiohalogenation of a HER2-Targeted Single-Domain Antibody Fragment Using a Novel Residualizing Prosthetic Agent. J Med Chem, 65(22), 15358–15373. https://doi.org/10.1021/acs.jmedchem.2c01331
Feng, Yutian, Samantha M. Sarrett, Rebecca L. Meshaw, Ganesan Vaidyanathan, Mike A. Cornejo, Brian M. Zeglis, and Michael R. Zalutsky. “Site-Specific Radiohalogenation of a HER2-Targeted Single-Domain Antibody Fragment Using a Novel Residualizing Prosthetic Agent.J Med Chem 65, no. 22 (November 24, 2022): 15358–73. https://doi.org/10.1021/acs.jmedchem.2c01331.
Feng Y, Sarrett SM, Meshaw RL, Vaidyanathan G, Cornejo MA, Zeglis BM, et al. Site-Specific Radiohalogenation of a HER2-Targeted Single-Domain Antibody Fragment Using a Novel Residualizing Prosthetic Agent. J Med Chem. 2022 Nov 24;65(22):15358–73.
Feng, Yutian, et al. “Site-Specific Radiohalogenation of a HER2-Targeted Single-Domain Antibody Fragment Using a Novel Residualizing Prosthetic Agent.J Med Chem, vol. 65, no. 22, Nov. 2022, pp. 15358–73. Pubmed, doi:10.1021/acs.jmedchem.2c01331.
Feng Y, Sarrett SM, Meshaw RL, Vaidyanathan G, Cornejo MA, Zeglis BM, Zalutsky MR. Site-Specific Radiohalogenation of a HER2-Targeted Single-Domain Antibody Fragment Using a Novel Residualizing Prosthetic Agent. J Med Chem. 2022 Nov 24;65(22):15358–15373.
Journal cover image

Published In

J Med Chem

DOI

EISSN

1520-4804

Publication Date

November 24, 2022

Volume

65

Issue

22

Start / End Page

15358 / 15373

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Single-Domain Antibodies
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Radiopharmaceuticals
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Female
  • Cell Line, Tumor
  • Breast Neoplasms