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Diagnosis of bladder cancer using 18F-labeled α-methyl-phenylalanine tracers in a mouse model

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Abstract

Objective

Although 2-18F-fluoro-2-deoxy-glucose (18F-FDG) has established roles in the diagnosis of a variety of cancers, it has limited value in the detection of primary/recurrent lesions in the bladder, mainly because of interference by the pooled radioactivity in the urine. Our previous study revealed promising properties of l- and d-2-18F-α-methyl-phenylalanine (2-18F-FAMP) as radiotracers; i.e., their rapid blood clearance and low renal accumulation. In the present study we evaluated the utility of l- and d-2-18F-FAMP for imaging bladder cancer in a mouse model.

Methods

We used the human bladder cancer cell line HT1376 to prepare a bladder cancer xenograft model in mice bearing both orthotopic and subcutaneous tumors. Biodistribution and PET imaging studies were performed at 1 and 3 h after injection of l-2-18F-FAMP or d-2-18F-FAMP. 18F-FDG was used as a control.

Results

At 1 h after injection, greater accumulations of both l-2-18F-FAMP and d-2-18F-FAMP were observed in the orthotopic tumors compared to 18F-FDG. The orthotopic tumor-to-muscle ratio of d-2-18F-FAMP was significantly higher than that of 18F-FDG (p < 0.01), because of the rapid blood clearance of d-2-18F-FAMP. l-2-18F-FAMP showed the highest subcutaneous tumor-to-muscle ratio (p < 0.01) due to its high subcutaneous tumor uptake. Compared to l-2-18F-FAMP, d-2-18F-FAMP exhibited faster clearance and lower kidney accumulation. In the PET imaging studies, l- and d-2-18F-FAMP both clearly visualized the orthotopic bladder tumors at 1 h after injection.

Conclusion

Our study showed that l-2-18F-FAMP and d-2-18F-FAMP have the potential to detect bladder cancer.

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Acknowledgements

We thank Mr. Takashi Ogasawara (Cyclotron Facility, Gunma University Hospital) for producing the 18F-FAMPs and 18F-FDG. No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, 371-8511, Japan

    Isa Mahendra, Tumenjargal Amartuvshin & Yoshito Tsushima

  2. Department of Bioimaging and Information Analysis, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, 371-8511, Japan

    Hirofumi Hanaoka & Aiko Yamaguchi

  3. Center for Applied Nuclear Science and Technology, National Nuclear Energy Agency of Indonesia, Tamansari 71, Bandung, West Java, 40132, Indonesia

    Isa Mahendra

  4. Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, 77054, USA

    Aiko Yamaguchi

  5. Research Program for Diagnostic and Molecular Imaging, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, 371-8511, Japan

    Yoshito Tsushima

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  1. Isa Mahendra
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  2. Hirofumi Hanaoka
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Correspondence to Hirofumi Hanaoka.

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Mahendra, I., Hanaoka, H., Yamaguchi, A. et al. Diagnosis of bladder cancer using 18F-labeled α-methyl-phenylalanine tracers in a mouse model. Ann Nucl Med 34, 329–336 (2020). https://doi.org/10.1007/s12149-020-01452-z

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  • DOI: https://doi.org/10.1007/s12149-020-01452-z

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