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.
- Blood-brain barrier disruption
- Focused ultrasound
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging