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Imaging malignant melanoma with 18F-5-FPN

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. 18F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide (18F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma.

Methods

18F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using 18F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with 18F-FDG. PET imaging with 18F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases.

Results

18F-5-FPN was successfully prepared with radiochemical yields of 5 – 10 %. Binding of 18F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. 18F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. 18F-5-FPN and 18F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of 18F-5-FPN was ten times higher than that of 18F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). 18F-5-FPN PET imaging also detected simulated lung metastases measuring 1 – 2 mm.

Conclusion

18F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity and favourable pharmacokinetics. 18F-5-FPN may be an ideal molecular probe for melanoma diagnosis and staging.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 81371626), and the Natural Science Foundation of Hubei Province of China for Distinguished Young Scholars (no. 2010CDA094).

We thank Dr. Guoping Yan and Dr. Biao Zhao of the School of Material Science and Engineering, Wuhan Institute of Technology, for their kind help in preparation of the labelling precursors. We also thank Dr. Qingguo Xie, Dr. Xiao Liang and Dr. Cheng Cheng of the School of Life Science and Technology, Huazhong University of Science and Technology, for their kind help in acquisition of images using the small-animal PET scanner.

Conflicts of interest

None.

Compliance with ethical standards

ᅟ

Funding

This work was supported by the National Natural Science Foundation of China (no. 81371626), and the Natural Science Foundation of Hubei Province of China for Distinguished Young Scholars (no. 2010CDA094).

Statement on the welfare of animals

All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Tongji Medical College of Huazhong University of Science and Technology.

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    Authors and Affiliations

    1. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Key Laboratory of Molecular Imaging, No. 1277 Jiefang Ave, Wuhan, 430022, China

      Hongyan Feng, Xiaotian Xia, Chongjiao Li, Yiling Song, Chunxia Qin, Qingyao Liu, Yongxue Zhang & Xiaoli Lan

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    1. Hongyan Feng
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    Correspondence to Xiaoli Lan.

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    Hongyan Feng and Xiaotian Xia contributed equally to this work.

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    Feng, H., Xia, X., Li, C. et al. Imaging malignant melanoma with 18F-5-FPN. Eur J Nucl Med Mol Imaging 43, 113–122 (2016). https://doi.org/10.1007/s00259-015-3134-2

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