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

doi:10.2967/jnumed.110.083071

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 journal › Article › peer-review

45 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 language	English
Pages (from-to)	478-484
Number of pages	7
Journal	Journal of Nuclear Medicine
Volume	52
Issue number	3
DOIs	https://doi.org/10.2967/jnumed.110.083071
Publication status	Published - Mar 1 2011
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

Access to Document

10.2967/jnumed.110.083071

Cite this

@article{82517ff724c64851a077ec6c6db6f1a4,

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

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.",

keywords = "Blood-brain barrier disruption, Focused ultrasound, Pharmacokinetics, Tc-DTPA, micro-SPECT",

author = "Yang, {Feng Yi} and Wang, {Hsin Ell} and Lin, {Guan Liang} and Teng, {Ming Che} and Lin, {Hui Hsien} and Wong, {Tai Tong} and Liu, {Ren Shyan}",

year = "2011",

month = mar,

day = "1",

doi = "10.2967/jnumed.110.083071",

language = "English",

volume = "52",

pages = "478--484",

journal = "Journal of Nuclear Medicine",

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publisher = "Society of Nuclear Medicine Inc.",

number = "3",

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T1 - Micro-SPECT/CT-based pharmacokinetic analysis of 99mTc- diethylenetriaminepentaacetic acid in rats with blood-brain barrier disruption induced by focused ultrasound

AU - Yang, Feng Yi

AU - Wang, Hsin Ell

AU - Lin, Guan Liang

AU - Teng, Ming Che

AU - Lin, Hui Hsien

AU - Wong, Tai Tong

AU - Liu, Ren Shyan

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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.

AB - 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.

KW - Blood-brain barrier disruption

KW - Focused ultrasound

KW - Pharmacokinetics

KW - Tc-DTPA

KW - micro-SPECT

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