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      ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer

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          Abstract

          Purpose

          Overexpression of CD146 in solid tumors has been linked to disease progression, invasion, and metastasis. In this study, we describe the generation of a 64Cu-labeled CD146-specific antibody for quantitative immunoPET imaging of CD146 expression in six lung cancer models.

          Methods

          The anti-CD146 antibody (YY146) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with 64Cu. 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 64Cu-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 64Cu-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.

          Results

          Flow cytometry and Western blot studies showed similar findings with H460 and H23 cells highly expressing CD146. Small differences in CD146 expression levels were found between A549, H4006, H522, and H358 cells. Tumor uptake of 64Cu-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 post-injection (n=4). Tumor uptake was lowest in the H522 model (4.1 ± 0.98 %ID/g at 48 h post-injection; n=4), while H4006, A549 and H358 exhibited similar uptake of 64Cu-NOTA-YY146. A positive correlation was found between tumor uptake of 64Cu-NOTA-YY146 (%ID/g) and relative CD146 expression (r 2=0.98, p<0.01). Ex vivo biodistribution corroborated the accuracy of PET data.

          Conclusions

          The strong correlation between tumor uptake of 64Cu-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.

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          Author and article information

          Journal
          101140988
          27055
          Eur J Nucl Med Mol Imaging
          Eur. J. Nucl. Med. Mol. Imaging
          European journal of nuclear medicine and molecular imaging
          1619-7070
          1619-7089
          10 June 2016
          25 June 2016
          November 2016
          01 November 2017
          : 43
          : 12
          : 2169-2179
          Affiliations
          [1 ]Department of Radiology, University of Wisconsin - Madison, WI 53705, USA
          [2 ]Department of Medical Physics, University of Wisconsin - Madison, WI 53705, USA
          [3 ]Department of Biomedical Engineering, University of Wisconsin - Madison, WI 53705, USA
          [4 ]University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA
          Author notes
          [* ]Corresponding Authors: Weibo Cai, Ph.D., Address: Department of Radiology, University of Wisconsin – Madison, Room 7137, 1111 Highland Ave., Madison, WI 53705-2275, USA. wcai@ 123456uwhealth.org ; Phone: 608-262-1749; Fax: 608-265-0614., Yunan Yang, M.D., Ph.D., Address: Department of Radiology, University of Wisconsin – Madison, Room 7148, 1111 Highland Ave., Madison, WI 53705-2275, USA. yunan.yang09@ 123456gmail.com ; Phone: 608-262-1749; Fax: 608-265-0614.
          Article
          PMC5050101 PMC5050101 5050101 nihpa793722
          10.1007/s00259-016-3442-1
          5050101
          27342417
          1da95295-5760-4cfb-817b-55b9e0c91647
          History
          Categories
          Article

          YY146,CD146,Positron emission tomography (PET),lung cancer,monoclonal antibody,molecular imaging

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