Micro-SPECT/CT-based pharmacokinetic analysis of 99mTc- diethylenetriaminepentaacetic acid in rats with blood-brain barrier disruption induced by focused ultrasound

Feng Yi Yang, Hsin Ell Wang, Guan Liang Lin, Ming Che Teng, Hui Hsien Lin, Tai-Tong Wong, Ren Shyan Liu

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

This study evaluated the pharmacokinetics of 99mTc- diethylenetriamine pentaacetate acid (99mTc-DTPA) after intravenous administration in healthy and F98 glioma-bearing F344 rats in the presence of blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). The pharmacokinetics of the healthy and tumor-containing brains after BBB-D were compared to identify the optimal time period for combined treatment. Methods: Healthy and F98 glioma-bearing rats were injected intravenously with Evans blue (EB) and 99mTc-DTPA; these treatments took place with or without BBB-D induced by transcranial FUS of 1 hemisphere of the brain. The permeability of the BBB was quantified by EB extravasation. Twelve rats were scanned for 2 h to estimate uptake of 99mTc radioactivity with respect to time for the pharmacokinetic analysis. Terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) staining was performed to examine tissue damage. Results: The accumulations of EB and 99mTc-DTPA in normal brains or brains with a tumor were significantly elevated after the intravenous injection when BBB-D was induced. The disruption-to-nondisruption ratio of the brains and the tumor-to-ipsilateral brain ratio of the tumors in terms of radioactivity reached a peak at 45 and 60 min, respectively. EB injection followed by sonication showed that there was an increase of about 2-fold in the tumor-to-ipsilateral brain EB ratio of the target tumors (7.36), compared with the control tumors (3.73). TUNEL staining showed no significant differences between the sonicated tumors and control tumors. Conclusion: This study demonstrates that 99mTc-DTPA micro-SPECT/CT can be used for the pharmacokinetic analysis of BBB-D induced by FUS. This method should be able to provide important information that will help with establishing an optimal treatment protocol for drug administration after FUS-induced BBB-D in clinical brain disease therapy.

Original languageEnglish
Pages (from-to)478-484
Number of pages7
JournalJournal of Nuclear Medicine
Volume52
Issue number3
DOIs
Publication statusPublished - Mar 1 2011
Externally publishedYes

Fingerprint

Evans Blue
Blood-Brain Barrier
Pharmacokinetics
Acids
Brain Neoplasms
Neoplasms
Brain
Glioma
Radioactivity
Staining and Labeling
Sonication
Inbred F344 Rats
Brain Diseases
Clinical Protocols
Intravenous Injections
Intravenous Administration
Single Photon Emission Computed Tomography Computed Tomography
Permeability
Therapeutics
Injections

Keywords

  • Tc-DTPA
  • Blood-brain barrier disruption
  • Focused ultrasound
  • micro-SPECT
  • Pharmacokinetics

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Micro-SPECT/CT-based pharmacokinetic analysis of 99mTc- diethylenetriaminepentaacetic acid in rats with blood-brain barrier disruption induced by focused ultrasound. / Yang, Feng Yi; Wang, Hsin Ell; Lin, Guan Liang; Teng, Ming Che; Lin, Hui Hsien; Wong, Tai-Tong; Liu, Ren Shyan.

In: Journal of Nuclear Medicine, Vol. 52, No. 3, 01.03.2011, p. 478-484.

Research output: Contribution to journalArticle

Yang, Feng Yi ; Wang, Hsin Ell ; Lin, Guan Liang ; Teng, Ming Che ; Lin, Hui Hsien ; Wong, Tai-Tong ; Liu, Ren Shyan. / Micro-SPECT/CT-based pharmacokinetic analysis of 99mTc- diethylenetriaminepentaacetic acid in rats with blood-brain barrier disruption induced by focused ultrasound. In: Journal of Nuclear Medicine. 2011 ; Vol. 52, No. 3. pp. 478-484.
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abstract = "This study evaluated the pharmacokinetics of 99mTc- diethylenetriamine pentaacetate acid (99mTc-DTPA) after intravenous administration in healthy and F98 glioma-bearing F344 rats in the presence of blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). The pharmacokinetics of the healthy and tumor-containing brains after BBB-D were compared to identify the optimal time period for combined treatment. Methods: Healthy and F98 glioma-bearing rats were injected intravenously with Evans blue (EB) and 99mTc-DTPA; these treatments took place with or without BBB-D induced by transcranial FUS of 1 hemisphere of the brain. The permeability of the BBB was quantified by EB extravasation. Twelve rats were scanned for 2 h to estimate uptake of 99mTc radioactivity with respect to time for the pharmacokinetic analysis. Terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) staining was performed to examine tissue damage. Results: The accumulations of EB and 99mTc-DTPA in normal brains or brains with a tumor were significantly elevated after the intravenous injection when BBB-D was induced. The disruption-to-nondisruption ratio of the brains and the tumor-to-ipsilateral brain ratio of the tumors in terms of radioactivity reached a peak at 45 and 60 min, respectively. EB injection followed by sonication showed that there was an increase of about 2-fold in the tumor-to-ipsilateral brain EB ratio of the target tumors (7.36), compared with the control tumors (3.73). TUNEL staining showed no significant differences between the sonicated tumors and control tumors. Conclusion: This study demonstrates that 99mTc-DTPA micro-SPECT/CT can be used for the pharmacokinetic analysis of BBB-D induced by FUS. This method should be able to provide important information that will help with establishing an optimal treatment protocol for drug administration after FUS-induced BBB-D in clinical brain disease therapy.",
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AU - Teng, Ming Che

AU - Lin, Hui Hsien

AU - Wong, Tai-Tong

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