Journal article
ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer
European journal of nuclear medicine and molecular imaging, Vol.43(12), pp.2169-2179
11/01/2016
DOI: 10.1007/s00259-016-3442-1
PMCID: PMC5050101
PMID: 27342417
Abstract
Overexpression of CD146 in solid tumors has been linked to disease progression, invasion, and metastasis. We describe the generation of a Cu-64-labeled CD146-specific antibody and its use for quantitative immunoPET imaging of CD146 expression in six lung cancer models.
The anti-CD146 antibody (YY146) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with Cu-64. CD146 expression was evaluated in six human lung cancer cell lines (A549, NCI-H358, NCI-H522, HCC4006, H23, and NCI-H460) by flow cytometry and quantitative western blot studies. The biodistribution and tumor uptake of Cu-64-NOTA-YY146 was assessed by sequential PET imaging in athymic nude mice bearing subcutaneous lung cancer xenografts. The correlation between CD146 expression and tumor uptake of Cu-64-NOTA-YY146 was evaluated by graphical software while ex vivo biodistribution and immunohistochemistry studies were performed to validate the accuracy of PET data and spatial expression of CD146.
Flow cytometry and western blot studies showed similar findings with H460 and H23 cells showing high levels of expression of CD146. Small differences in CD146 expression levels were found among A549, H4006, H522, and H358 cells. Tumor uptake of Cu-64-NOTA-YY146 was highest in CD146-expressing H460 and H23 tumors, peaking at 20.1 +/- 2.86 and 11.6 +/- 2.34 %ID/g at 48 h after injection (n = 4). Tumor uptake was lowest in the H522 model (4.1 +/- 0.98 %ID/g at 48 h after injection; n = 4), while H4006, A549 and H358 exhibited similar uptake of Cu-64-NOTA-YY146. A positive correlation was found between tumor uptake of Cu-64-NOTA-YY146 (%ID/g) and relative CD146 expression (r (2) = 0.98, p < 0.01). Ex vivo biodistribution confirmed the accuracy of the PET data.
The strong correlation between tumor uptake of Cu-64-NOTA-YY146 and CD146 expression demonstrates the potential use of this radiotracer for imaging tumors that elicit varying levels of CD146. In the future, this tool may promote enhanced monitoring of therapeutic response and improved patient stratification.
Details
- Title: Subtitle
- ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer
- Creators
- Haiyan Sun - University of Wisconsin–MadisonChristopher G. England - University of Wisconsin–MadisonReinier Hernandez - University of Wisconsin–MadisonStephen A. Graves - University of Wisconsin–MadisonRebecca L. Majewski - Univ Wisconsin, Dept Biomed Engn, Madison, WI 53705 USAAnyanee Kamkaew - University of Wisconsin–MadisonDawei Jiang - University of Wisconsin–MadisonTodd E. Barnhart - University of Wisconsin–MadisonYunan Yang - University of Wisconsin–MadisonWeibo Cai - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- European journal of nuclear medicine and molecular imaging, Vol.43(12), pp.2169-2179
- DOI
- 10.1007/s00259-016-3442-1
- PMID
- 27342417
- PMCID
- PMC5050101
- NLM abbreviation
- Eur J Nucl Med Mol Imaging
- ISSN
- 1619-7070
- eISSN
- 1619-7089
- Publisher
- Springer Nature
- Number of pages
- 11
- Grant note
- T32GM008349 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) University of Wisconsin - Madison 1R01CA169365; P30CA014520; T32CA009206; T32GM008349 / National Institutes of Health (NIBIB/NCI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA DGE-1256259 / National Science Foundation; National Science Foundation (NSF) 125246-RSG-13-099-01-CCE / American Cancer Society R01CA169365 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 11/01/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383280902771
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