Top

Molecular Imaging and Biology

Published in:

01-04-2016 | Research Article

Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Authors: E. de Boer, S. Samuel, D. N. French, J. M. Warram, T. R. Schoeb, E. L. Rosenthal, K. R. Zinn

Published in: Molecular Imaging and Biology | Issue 2/2016

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.

Available only for authorised users

van Dam GM, Themelis G, Crane LM et al (2011) Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med 17:1315–1319CrossRefPubMed

Zinn KR, Korb M, Samuel S et al (2015) IND-directed safety and biodistribution study of intravenously injected cetuximab-IRDye800 in cynomolgus macaques. Mol Imaging Biol 17:49–57CrossRefPubMedPubMedCentral

Day KE, Sweeny L, Kulbersh B et al (2013) Preclinical comparison of near-infrared-labeled cetuximab and panitumumab for optical imaging of head and neck squamous cell carcinoma. Mol Imaging Biol 15:722–729CrossRefPubMedPubMedCentral

Heath CH, Deep NL, Sweeny L et al (2012) Use of panitumumab-IRDye800 to image microscopic head and neck cancer in an orthotopic surgical model. Ann Surg Oncol 19:3879–3887CrossRefPubMedPubMedCentral

Terwisscha van Scheltinga AG, van Dam GM, Nagengast WB et al (2011) Intraoperative near-infrared fluorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies. J Nucl Med 52:1778–1785CrossRefPubMed

Korb ML, Hartman YE, Kovar J et al (2014) Use of monoclonal antibody-IRDye800CW bioconjugates in the resection of breast cancer. J Surg Res 188:119–128CrossRefPubMedPubMedCentral

van Dongen GA, Visser GW, Vrouenraets MB (2004) Photosensitizer-antibody conjugates for detection and therapy of cancer. Adv Drug Deliv Rev 56:31–52CrossRefPubMed

Mitsunaga M, Ogawa M, Kosaka N et al (2011) Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nat Med 17:1685–1691CrossRefPubMedPubMedCentral

de Boer E, Warram JM, Hartmans E et al (2014) A standardized light-emitting diode device for photoimmunotherapy. J Nucl Med 55:1893–1898CrossRefPubMed

10.

Mitsunaga M, Nakajima T, Sano K et al (2012) Immediate in vivo target-specific cancer cell death after near infrared photoimmunotherapy. BMC Cancer 12:1471–2407CrossRef

11.

Nakajima T, Sano K, Choyke PL, Kobayashi H (2013) Improving the efficacy of photoimmunotherapy (PIT) using a cocktail of antibody conjugates in a multiple antigen tumor model. Theranostics 3:357–365CrossRefPubMedPubMedCentral

12.

Rogers SJ, Harrington KJ, Rhys-Evans P et al (2005) Biological significance of c-erbB family oncogenes in head and neck cancer. Cancer Metastasis Rev 24:47–69CrossRefPubMed

13.

Giusti RM, Shastri KA, Cohen MH et al (2007) FDA drug approval summary: panitumumab (Vectibix). Oncologist 12:577–583CrossRefPubMed

14.

Kim H, Chaudhuri TR, Buchsbaum DJ et al (2007) High-resolution single-photon emission computed tomography and X-ray computed tomography imaging of Tc-99m-labeled anti-DR5 antibody in breast tumor xenografts. Mol Cancer Ther 6:866–875CrossRefPubMed

15.

de Boer E, Warram JM, Tucker MD et al (2015) In vivo fluorescence immunohistochemistry: localization of fluorescently labeled cetuximab in squamous cell carcinomas. Sci Rep 5:10169CrossRefPubMed

16.

Tichauer KM, Samkoe KS, Gunn JR et al (2014) Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging. Nat Med 20:1348–1353CrossRefPubMedPubMedCentral

Title: Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques
Authors: E. de Boer
S. Samuel
D. N. French
J. M. Warram
T. R. Schoeb
E. L. Rosenthal
K. R. Zinn
Publication date: 01-04-2016
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 2/2016
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-015-0892-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2016

The Synergistic Effect of Selumetinib/Docetaxel Combination Therapy Monitored by [18 F]FDG/[18 F]FLT PET and Diffusion-Weighted Magnetic Resonance Imaging in a Colorectal Tumor Xenograft Model

Establishing On-Site Reference Values for 123I-FP-CIT SPECT (DaTSCAN®) Using a Cohort of Individuals with Non-Degenerative Conditions

Predicting Response to Therapy for Autoimmune and Inflammatory Diseases Using a Folate Receptor-Targeted Near-Infrared Fluorescent Imaging Agent

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

Chemical Exchange Saturation Transfer (CEST) MR Technique for Liver Imaging at 3.0 Tesla: an Evaluation of Different Offset Number and an After-Meal and Over-Night-Fast Comparison

The PGRMC1 Protein Level Correlates with the Binding Activity of a Sigma-2 Fluorescent Probe (SW120) in Rat Brain Cells