Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW

Hao Hong; Yin Zhang; Gregory W. Severin; Yunan Yang; Jonathan W. Engle; Gang Niu; Robert J. Nickles; Xiaoyuan Chen; Bryan R. Leigh; Todd E. Barnhart; Weibo Cai

doi:10.1021/mp300277f

Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW

Hao Hong, Yin Zhang, Gregory W. Severin, Yunan Yang, Jonathan W. Engle, Gang Niu, Robert J. Nickles, Xiaoyuan Chen, Bryan R. Leigh, Todd E. Barnhart, Weibo Cai

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and 89Zr to yield 89Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female mice to establish the tumor model. Bioluminescence imaging (BLI) was carried out to noninvasively monitor the lung tumor burden. PET imaging revealed that 4T1 lung tumor uptake of 89Zr-Df-TRC105- 800CW was 8.7 ± 1.4, 10.9 ± 0.5, and 9.7 ± 1.1% ID/g at 4, 24, and 48 h postinjection (n = 4), with excellent tumor contrast. Biodistribution studies, blocking, control studies with 89Zr-Df- cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD105 specificity of the tracer. Broad clinical potential of TRC105-based agents was shown in many tumor types, which also enabled early detection of small metastasis and intraoperative guidance for tumor removal. © 2012 American Chemical Society.

Original language	English
Journal	Molecular Pharmaceutics
Volume	9
Issue number	8
Pages (from-to)	2339-2349
Number of pages	11
ISSN	1543-8384
DOIs	https://doi.org/10.1021/mp300277f
Publication status	Published - 2012
Externally published	Yes

Keywords

Pharmaceutical Science
Molecular Medicine
Drug Discovery
89Zr
breast cancer
CD105 (endoglin)
lung metastasis
near-infrared fluorescence (NIRF)
positron emission tomography (PET)
tumor angiogenesis
cetuximab
deferoxamine
deferoxamine cetuximab IRDye 800CW zr 89
deferoxamine monoclonal antibody TRC 105 IRDye 800CW zr 89
endoglin
monoclonal antibody
tracer
trc 105
unclassified drug
zirconium
zirconium 89
animal cell
animal experiment
animal model
animal tissue
article
bioluminescence
controlled study
drug distribution
drug synthesis
drug uptake
female
human
human cell
mouse
near infrared fluorescence
nonhuman
positron emission tomography
priority journal
radiation dose
tumor volume

Access to Document

10.1021/mp300277f

Cite this

Hong, H., Zhang, Y., Severin, G. W., Yang, Y., Engle, J. W., Niu, G., Nickles, R. J., Chen, X., Leigh, B. R., Barnhart, T. E., & Cai, W. (2012). Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW. Molecular Pharmaceutics, 9(8), 2339-2349. https://doi.org/10.1021/mp300277f

Hong, Hao ; Zhang, Yin ; Severin, Gregory W. ; Yang, Yunan ; Engle, Jonathan W. ; Niu, Gang ; Nickles, Robert J. ; Chen, Xiaoyuan ; Leigh, Bryan R. ; Barnhart, Todd E. ; Cai, Weibo. / Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW. In: Molecular Pharmaceutics. 2012 ; Vol. 9, No. 8. pp. 2339-2349.

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title = "Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW",

abstract = "Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and 89Zr to yield 89Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female mice to establish the tumor model. Bioluminescence imaging (BLI) was carried out to noninvasively monitor the lung tumor burden. PET imaging revealed that 4T1 lung tumor uptake of 89Zr-Df-TRC105- 800CW was 8.7 ± 1.4, 10.9 ± 0.5, and 9.7 ± 1.1% ID/g at 4, 24, and 48 h postinjection (n = 4), with excellent tumor contrast. Biodistribution studies, blocking, control studies with 89Zr-Df- cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD105 specificity of the tracer. Broad clinical potential of TRC105-based agents was shown in many tumor types, which also enabled early detection of small metastasis and intraoperative guidance for tumor removal. {\textcopyright} 2012 American Chemical Society.",

keywords = "Pharmaceutical Science, Molecular Medicine, Drug Discovery, 89Zr, breast cancer, CD105 (endoglin), lung metastasis, near-infrared fluorescence (NIRF), positron emission tomography (PET), tumor angiogenesis, cetuximab, deferoxamine, deferoxamine cetuximab IRDye 800CW zr 89, deferoxamine monoclonal antibody TRC 105 IRDye 800CW zr 89, endoglin, monoclonal antibody, tracer, trc 105, unclassified drug, zirconium, zirconium 89, animal cell, animal experiment, animal model, animal tissue, article, bioluminescence, controlled study, drug distribution, drug synthesis, drug uptake, female, human, human cell, mouse, near infrared fluorescence, nonhuman, positron emission tomography, priority journal, radiation dose, tumor volume",

author = "Hao Hong and Yin Zhang and Severin, {Gregory W.} and Yunan Yang and Engle, {Jonathan W.} and Gang Niu and Nickles, {Robert J.} and Xiaoyuan Chen and Leigh, {Bryan R.} and Barnhart, {Todd E.} and Weibo Cai",

year = "2012",

doi = "10.1021/mp300277f",

language = "English",

volume = "9",

pages = "2339--2349",

journal = "Molecular Pharmaceutics",

issn = "1543-8384",

publisher = "American Chemical Society",

number = "8",

}

Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW. / Hong, Hao; Zhang, Yin; Severin, Gregory W.; Yang, Yunan; Engle, Jonathan W.; Niu, Gang; Nickles, Robert J.; Chen, Xiaoyuan; Leigh, Bryan R.; Barnhart, Todd E.; Cai, Weibo.

In: Molecular Pharmaceutics, Vol. 9, No. 8, 2012, p. 2339-2349.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW

AU - Hong, Hao

AU - Zhang, Yin

AU - Severin, Gregory W.

AU - Yang, Yunan

AU - Engle, Jonathan W.

AU - Niu, Gang

AU - Nickles, Robert J.

AU - Chen, Xiaoyuan

AU - Leigh, Bryan R.

AU - Barnhart, Todd E.

AU - Cai, Weibo

PY - 2012

Y1 - 2012

N2 - Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and 89Zr to yield 89Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female mice to establish the tumor model. Bioluminescence imaging (BLI) was carried out to noninvasively monitor the lung tumor burden. PET imaging revealed that 4T1 lung tumor uptake of 89Zr-Df-TRC105- 800CW was 8.7 ± 1.4, 10.9 ± 0.5, and 9.7 ± 1.1% ID/g at 4, 24, and 48 h postinjection (n = 4), with excellent tumor contrast. Biodistribution studies, blocking, control studies with 89Zr-Df- cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD105 specificity of the tracer. Broad clinical potential of TRC105-based agents was shown in many tumor types, which also enabled early detection of small metastasis and intraoperative guidance for tumor removal. © 2012 American Chemical Society.

AB - Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and 89Zr to yield 89Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female mice to establish the tumor model. Bioluminescence imaging (BLI) was carried out to noninvasively monitor the lung tumor burden. PET imaging revealed that 4T1 lung tumor uptake of 89Zr-Df-TRC105- 800CW was 8.7 ± 1.4, 10.9 ± 0.5, and 9.7 ± 1.1% ID/g at 4, 24, and 48 h postinjection (n = 4), with excellent tumor contrast. Biodistribution studies, blocking, control studies with 89Zr-Df- cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD105 specificity of the tracer. Broad clinical potential of TRC105-based agents was shown in many tumor types, which also enabled early detection of small metastasis and intraoperative guidance for tumor removal. © 2012 American Chemical Society.

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KW - article

KW - bioluminescence

KW - controlled study

KW - drug distribution

KW - drug synthesis

KW - drug uptake

KW - female

KW - human

KW - human cell

KW - mouse

KW - near infrared fluorescence

KW - nonhuman

KW - positron emission tomography

KW - priority journal

KW - radiation dose

KW - tumor volume

U2 - 10.1021/mp300277f

DO - 10.1021/mp300277f

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C2 - 22784250

VL - 9

SP - 2339

EP - 2349

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

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