Skip to main content

Site-Specific and Residualizing Linker for 18F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment.

Publication ,  Journal Article
Zhou, Z; Meshaw, R; Zalutsky, MR; Vaidyanathan, G
Published in: J Nucl Med
November 2021

Single-domain antibody fragments (sdAbs) are promising vectors for immuno-PET; however, better methods for labeling sdAbs with 18F are needed. Herein, we evaluate a site-specific strategy using an 18F residualizing motif and the anti-epidermal growth factor receptor 2 (HER2) sdAb 5F7 bearing an engineered C-terminal GGC tail (5F7GGC). Methods: 5F7GGC was site-specifically attached with a tetrazine-bearing agent via thiol-maleimide reaction. The resultant conjugate was labeled with 18F by inverse electron demand Diels-Alder cycloaddition with a trans-cyclooctene attached to 6-18F-fluoronicotinoyl moiety via a renal brush border enzyme-cleavable linker and a PEG4 chain (18F-5F7GGC). For comparisons, 5F7 sdAb was labeled using the prototypical residualizing agent, N-succinimidyl 3-(guanidinomethyl)-5-125I-iodobenzoate (iso-125I-SGMIB). The 2 labeled sdAbs were compared in paired-label studies performed in the HER2-expressing BT474M1 breast carcinoma cell line and athymic mice bearing BT474M1 subcutaneous xenografts. Small-animal PET/CT imaging after administration of 18F-5F7GGC in the above mouse model was also performed. Results:18F-5F7GGC was synthesized in an overall radiochemical yield of 8.9% ± 3.2% with retention of HER2 binding affinity and immunoreactivity. The total cell-associated and intracellular activity for 18F-5F7GGC was similar to that for coincubated iso-125I-SGMIB-5F7. Likewise, the uptake of 18F-5F7GGC in BT474M1 xenografts in mice was similar to that for iso-125I-SGMIB-5F7; however, 18F-5F7GGC exhibited significantly more rapid clearance from the kidney. Small-animal PET/CT imaging confirmed high uptake and retention in the tumor with very little background activity at 3 h except in the bladder. Conclusion: This site-specific and residualizing 18F-labeling strategy could facilitate clinical translation of 5F7 anti-HER2 sdAb as well as other sdAbs for immuno-PET.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Nucl Med

DOI

EISSN

1535-5667

Publication Date

November 2021

Volume

62

Issue

11

Start / End Page

1624 / 1630

Location

United States

Related Subject Headings

  • Single-Domain Antibodies
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Positron Emission Tomography Computed Tomography
  • Nuclear Medicine & Medical Imaging
  • Humans
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhou, Z., Meshaw, R., Zalutsky, M. R., & Vaidyanathan, G. (2021). Site-Specific and Residualizing Linker for 18F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment. J Nucl Med, 62(11), 1624–1630. https://doi.org/10.2967/jnumed.120.261446
Zhou, Zhengyuan, Rebecca Meshaw, Michael R. Zalutsky, and Ganesan Vaidyanathan. “Site-Specific and Residualizing Linker for 18F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment.J Nucl Med 62, no. 11 (November 2021): 1624–30. https://doi.org/10.2967/jnumed.120.261446.
Zhou, Zhengyuan, et al. “Site-Specific and Residualizing Linker for 18F Labeling with Enhanced Renal Clearance: Application to an Anti-HER2 Single-Domain Antibody Fragment.J Nucl Med, vol. 62, no. 11, Nov. 2021, pp. 1624–30. Pubmed, doi:10.2967/jnumed.120.261446.

Published In

J Nucl Med

DOI

EISSN

1535-5667

Publication Date

November 2021

Volume

62

Issue

11

Start / End Page

1624 / 1630

Location

United States

Related Subject Headings

  • Single-Domain Antibodies
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Positron Emission Tomography Computed Tomography
  • Nuclear Medicine & Medical Imaging
  • Humans
  • 3202 Clinical sciences
  • 1103 Clinical Sciences