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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 9/2017

01-08-2017 | Original Article

Inter-heterogeneity and intra-heterogeneity of αvβ3 in non-small cell lung cancer and small cell lung cancer patients as revealed by 68Ga-RGD2 PET imaging

Authors: Fei Kang, Zhe Wang, Guoquan Li, Shengjun Wang, Daliang Liu, Mingru Zhang, Mingxuan Zhao, Weidong Yang, Jing Wang

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2017

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Abstract

Purpose

Integrin αvβ3 is the therapeutic target of the anti-angiogenic drug cilengitide. The objective of this study was to compare αvβ3 levels in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients, by using the positron emission tomography (PET) tracer 68Ga-labeled dimerized-RGD (68Ga-RGD2).

Methods

Thirty-one patients with pathologically confirmed lung cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were acquired using 68Ga-RGD2.18F-FDG PET/CT images were also acquired on the consecutive day as reference. The standard uptake values (SUV) and the tumor/nontarget (T/NT) values were quantitatively compared. Expression of the angiogenesis marker αvβ3 in NSCLC and SCLC lesions was analyzed by immunohistochemistry.

Results

The 18F-FDG SUVmax and the SUVmean were not significantly different between NSCLC and SCLC patients. The 68Ga-RGD2 uptake of SCLC patients was at background levels in both SUV and T/NT measurements and was significantly lower than that of NSCLC patients. The range value of 68Ga-RGD2 SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively. Heterogeneity between primary lesions and putative distant metastases was also observed in some NSCLC cases. Immunostaining showed that αvβ3 integrin was expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples had negative expression.

Conclusions

The uptake of 68Ga-RGD2 in SCLC patients is significantly lower than that in NSCLC patients, indicating a lower αvβ3 target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of αvβ3 also exist in both NSCLC and SCLC. Such inter- and intra-heterogeneity of αvβ3 may potentially improve current applications of αvβ3-targeted therapy and diagnostic imaging in lung cancer.
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Metadata
Title
Inter-heterogeneity and intra-heterogeneity of αvβ3 in non-small cell lung cancer and small cell lung cancer patients as revealed by 68Ga-RGD2 PET imaging
Authors
Fei Kang
Zhe Wang
Guoquan Li
Shengjun Wang
Daliang Liu
Mingru Zhang
Mingxuan Zhao
Weidong Yang
Jing Wang
Publication date
01-08-2017
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2017
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3696-2

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