Micro-SPECT/CT with 99mTc-diethylenetriamine pentaacetate acid (99mTc-DTPA) can be used for the pharmacokinetic analysis of blood-brain barrier disruption induced by focused ultrasound (FUS), and could help with establishing an optimal treatment protocol for drug administration in clinical brain disease therapy, according to a study published in this month's Journal of Nuclear Medicine.
The study evaluated the pharmacokinetics of 99mTc-DTPA after intravenous administration in healthy and F98 glioma-bearing rats in the presence of blood-brain barrier disruption induced by FUS.
The pharmacokinetics of the healthy and tumor-containing brains after blood–brain barrier disruption were compared to identify the optimal time period for combined treatment by Feng-Yi Yang, PhD, assistant professor at the department of biomedical imaging and radiological sciences, National Yang-Ming University in Taipei, Taiwan and colleagues.
The permeability of the blood–brain barrier disruption was quantified by Evans blue extravasation. Twelve rats were scanned by Yang and colleagues for two hours to estimate uptake of 99mTc radioactivity with respect to time for the pharmacokinetic analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to examine tissue damage.
The researchers found that the accumulations of Evans blue and 99mTc-DTPA in normal brains or brains with a tumor were significantly elevated after the intravenous injection when blood–brain barrier disruption 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 minutes, respectively, according to Yang and colleagues.
Evans blue injection followed by sonication showed that there was an increase of about two-fold in the tumor-to-ipsilateral brain ratio of the target tumors, compared with the control tumors. However, TUNEL staining showed no significant differences between the sonicated tumors and control tumors, wrote the authors.
99mTc-DTPA micro-SPECT/CT showed that FUS not only significantly increased the permeability of the blood-brain barrier disruption at the sonicated site but also significantly elevated the lesion-to-normal brain ratio in the focal region.
“This noninvasive approach offers a good assessment of the extent of blood-brain barrier disruption and may be useful as a way of identifying an optimal window for effective Boron neutron capture therapy or other brain disease treatments that will have minimal negative side effects,” concluded the authors.