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

Akinori Takenaka, Yoshitaka Inui, Yuichi Kimura, Chikara Miyake, Yoichi Fujiyama, Takashi Yamada, Nobuya Hashizume, Takashi Kato, Kengo Ito, Hiroshi Toyama

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)586-593
Number of pages8
JournalAnnals of Nuclear Medicine
Volume33
Issue number8
DOIs
Publication statusPublished - 01-08-2019

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Positron-Emission Tomography
Glucose
Radioactivity
X-Ray Computed Tomography Scanners
Radiopharmaceuticals
Isoflurane
Fluorodeoxyglucose F18
Femoral Artery
Blood Volume
Catheters
Anesthesia
Injections

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Takenaka, Akinori ; Inui, Yoshitaka ; Kimura, Yuichi ; Miyake, Chikara ; Fujiyama, Yoichi ; Yamada, Takashi ; Hashizume, Nobuya ; Kato, Takashi ; Ito, Kengo ; Toyama, Hiroshi. / Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET. In: Annals of Nuclear Medicine. 2019 ; Vol. 33, No. 8. pp. 586-593.
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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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Takenaka, A, Inui, Y, Kimura, Y, Miyake, C, Fujiyama, Y, Yamada, T, Hashizume, N, Kato, T, Ito, K & Toyama, H 2019, 'Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET', Annals of Nuclear Medicine, vol. 33, no. 8, pp. 586-593. https://doi.org/10.1007/s12149-019-01368-3

Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET. / Takenaka, Akinori; Inui, Yoshitaka; Kimura, Yuichi; Miyake, Chikara; Fujiyama, Yoichi; Yamada, Takashi; Hashizume, Nobuya; Kato, Takashi; Ito, Kengo; Toyama, Hiroshi.

In: Annals of Nuclear Medicine, Vol. 33, No. 8, 01.08.2019, p. 586-593.

Research output: Contribution to journalArticle

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T1 - Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET

AU - Takenaka, Akinori

AU - Inui, Yoshitaka

AU - Kimura, Yuichi

AU - Miyake, Chikara

AU - Fujiyama, Yoichi

AU - Yamada, Takashi

AU - Hashizume, Nobuya

AU - Kato, Takashi

AU - Ito, Kengo

AU - Toyama, Hiroshi

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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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