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Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET

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Abstract

Objective

The objective of the present study was to develop a fully automated blood sampling system for kinetic analysis in mice positron emission tomography (PET) studies. Quantitative PET imaging requires radioactivity concentrations in arterial plasma to estimate the behavior of an administered radiopharmaceutical in target organs. Conventional manual blood sampling has several drawbacks, such as the need for troubleshooting in regard to blood collection, necessary personnel, and the radiation exposure dose. We recently developed and verified the operability of a fully automated blood sampling system (automatic blood dispensing system—ABDS). Here, we report the results of fully quantitative measurements of the cerebral metabolic rate of glucose (CMRglc) in mice using the ABDS.

Methods

Under 1% isoflurane anesthesia, a catheter was inserted into the femoral artery of nine wild-type male mice. Immediately after injection of 18F-fluorodeoxyglucose (FDG) (13.2 ± 3.93 MBq in 0.1 mL saline), arterial blood samples were drawn using the ABDS and then analyzed using CD-Well, a system we previously developed that can measure radioactivity concentration (Bq/μL) using a few microliters of blood in the plasma and whole blood separately. In total, 16 blood samplings were conducted in 60 min as follows: 10 s × 9; 70 s × 2; 120 s × 1; 250 s × 1; 10 min × 2; and 30 min × 1. Dynamic PET scans were conducted concurrently using a small-animal PET/computed tomography (CT) (PET/CT) scanner. Full kinetics modeling using a two-tissue–three-compartment model was applied to calculate CMRglc. Blood volume was also estimated.

Results

No significant differences were observed between the manual and ABDS measurements. A proportional error was detected only for plasma. The mean ± standard deviation CMRglc value in the mice was 5.43 ± 1.98 mg/100 g/min (30.2 ± 11 μmol/min/100 g), consistent with a previous report.

Conclusions

The automated microliter-ordered blood sampling system developed in the present study appears to be useful for absolute quantification of CMRglc in mice PET studies.

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Acknowledgements

This work was supported by JSPS Grant-in-Aid for Young Scientists (B) Grant Number JP15K19823 in 2015–2018.

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Authors and Affiliations

  1. Department of Radiology, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan

    Akinori Takenaka, Takashi Kato & Kengo Ito

  2. Department of Radiology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan

    Yoshitaka Inui & Hiroshi Toyama

  3. Department of Computational Systems Biology, Faculty of Biology-Oriented, Science and Technology, Kindai University, 930 Nishimitani, Kinokawa, Wakayama, 649-6493, Japan

    Yuichi Kimura

  4. Technology Research Laboratory, Shimadzu Corporation, 3-9-4 Hikaridai, Seika, Souraku, Kyoto, 619-0237, Japan

    Chikara Miyake & Yoichi Fujiyama

  5. Department of Human Life Sciences, Nagoya University of Economics, 61-1 Uchikubo, Inuyama, Aichi, 484-8504, Japan

    Takashi Yamada

  6. Technology Research Laboratory, Shimadzu Corporation, 1 Nishinokyokuwabara, Nakagyo-ku, Kyoto, 604-8442, Japan

    Nobuya Hashizume

  7. Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan

    Takashi Kato & Kengo Ito

Authors
  1. Akinori Takenaka
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  2. Yoshitaka Inui
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  3. Yuichi Kimura
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  4. Chikara Miyake
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  5. Yoichi Fujiyama
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  6. Takashi Yamada
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  7. Nobuya Hashizume
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  8. Takashi Kato
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  9. Kengo Ito
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  10. Hiroshi Toyama
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Correspondence to Akinori Takenaka.

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Takenaka, A., Inui, Y., Kimura, Y. et al. Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET. Ann Nucl Med 33, 586–593 (2019). https://doi.org/10.1007/s12149-019-01368-3

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  • DOI: https://doi.org/10.1007/s12149-019-01368-3

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