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Development of Diagnostic Techniques for Early Rheumatoid Arthritis Using Positron Emission Tomography with [11C]PK11195 and [11C]Ketoprofen Tracers

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Abstract

Purpose

In vivo detection of pathological insults during the early stages of rheumatoid synovitis is essential to allow early anti-inflammatory treatment for prevention of joint destruction. Whether rheumatoid synovitis pathology and the efficacy of therapies can be visualized by positron emission tomography (PET) tracers specific to the inflammatory process was investigated.

Procedures

Using a collagen-induced experimental rat model of rheumatoid arthritis, in vivo imaging using the PET tracers [11C]PK11195, which binds to the translocator protein mainly expressed on myeloid cells, and [11C]ketoprofen, for cyclooxygenase imaging, was performed. To evaluate therapeutic efficacy, model animals were administered the tumour necrosis factor alpha blocker etanercept subcutaneously.

Results

[11C]PK11195 and [11C]ketoprofen uptakes were significantly higher in inflamed paws of collagen-induced arthritis rats than in normal rats. The data showed a correlation between tracer uptake values and paw swelling. After treatment with etanercept, [11C]ketoprofen uptake was significantly lower in treated animals than in untreated ones, whereas [11C]PK11195 uptake in the inflamed regions was comparable to that in the untreated group.

Conclusions

With [11C]PK11195 and [11C]ketoprofen tracers, non-invasive in vivo PET imaging for rheumatoid synovitis can provide diagnostic evidence of early synovitis and allow monitoring inflammatory cell activity during treatment.

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Acknowledgements

The authors would like to thank Drs. Hitoshi Goto and Kohji Tanaka for their useful advice and comments.

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Authors and Affiliations

  1. RIKEN Center for Life Science Technologies, 6-7-3 Minatojima Minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan

    Satoshi Nozaki, Miki Goto, Aya Mawatari, Yuka Nakatani, Emi Hayashinaka, Yasuhiro Wada, Hisashi Doi & Yasuyoshi Watanabe

  2. Department of Molecular and Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd, Kobe, Hyogo, Japan

    Naoko Ozaki & Shinobu Suzuki

  3. Department of Physiology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Yasuyoshi Watanabe

Authors
  1. Satoshi Nozaki
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  2. Naoko Ozaki
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  3. Shinobu Suzuki
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  4. Miki Goto
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  5. Aya Mawatari
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  6. Yuka Nakatani
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  7. Emi Hayashinaka
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  8. Yasuhiro Wada
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  9. Hisashi Doi
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  10. Yasuyoshi Watanabe
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Corresponding author

Correspondence to Satoshi Nozaki.

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Conflict of Interest

Naoko Ozaki and Shinobu Suzuki were employees of Nippon Boehringer Ingelheim Co., Ltd. The other authors declare that they have no conflicts of interest. This study was supported in part by a research grant from Nippon Boehringer Ingelheim Co., Ltd., (Tokyo, Japan) to Yasuyoshi Watanabe.

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Nozaki, S., Ozaki, N., Suzuki, S. et al. Development of Diagnostic Techniques for Early Rheumatoid Arthritis Using Positron Emission Tomography with [11C]PK11195 and [11C]Ketoprofen Tracers. Mol Imaging Biol 19, 746–753 (2017). https://doi.org/10.1007/s11307-016-1039-5

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  • DOI: https://doi.org/10.1007/s11307-016-1039-5

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