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Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

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Abstract

Purpose

The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques.

Procedures

Total IR700 and intact cetuximab-IR700 were measured in 51 tissues at 2 and 14 days after intravenous injection of 40 and 80 mg/kg cetuximab-IR700, respectively, and compared with an unlabeled cetuximab-dosed control group (two each per sex per time point per group).

Results

The IR700 retrieved from all tissues at 2 and 14 days after dosing was estimated at 34.9 ± 1.8 and 2.53 ± 0.67 % of the total dose, respectively. The tissues with the highest levels of intact cetuximab-IR700 at 2 days after dosing were the blood, lung, and skin. Formalin-fixed paraffin-embedded tissue sections at 2 days after dosing showed the highest IR700 signals in the axillary lymph node, mammary gland, and gall bladder.

Conclusions

Both IR700 and intact cetuximab-IR700 biodistributions were consistent with known epidermal growth factor receptor (EGFR) expression, and changes between 2 and 14 days were consistent with rapid metabolism and excretion of the cetuximab-IR700.

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Acknowledgments

This work was supported by Aspyrian Therapeutics LLC, the UAB Comprehensive Cancer Center small animal imaging shared facility (5P30CA013148), and an equipment loan from LI-COR Biosciences. Authors would like to thank Miguel Garcia-Guzman for his input in this study.

Compliance with Ethical Standards

ᅟ

Conflict of Interest

Dr. K. R. Zinn reports grants from Aspyrian Therapeutics, during the conduct of the study.

Ethical Approval

All applicable institutional and/or national guidelines for the care and use of animals were followed.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

    E. de Boer & J. M. Warram

  2. Department of Surgery, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands

    E. de Boer

  3. Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35294, USA

    S. Samuel, D. N. French & K. R. Zinn

  4. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    T. R. Schoeb

  5. Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA

    E. L. Rosenthal

Authors
  1. E. de Boer
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  2. S. Samuel
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  3. D. N. French
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  4. J. M. Warram
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  5. T. R. Schoeb
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  6. E. L. Rosenthal
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  7. K. R. Zinn
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Corresponding author

Correspondence to K. R. Zinn.

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de Boer, E., Samuel, S., French, D.N. et al. Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques. Mol Imaging Biol 18, 232–242 (2016). https://doi.org/10.1007/s11307-015-0892-y

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  • DOI: https://doi.org/10.1007/s11307-015-0892-y

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