PT  - JOURNAL ARTICLE
AU  - Feng-Yi Yang
AU  - Wen-Yuan Chang
AU  - Jia-Je Li
AU  - Hsin-Ell Wang
AU  - Jyh-Cheng Chen
AU  - Chi-Wei Chang
TI  - Pharmacokinetic Analysis and Uptake of <sup>18</sup>F-FBPA-Fr After Ultrasound-Induced Blood–Brain Barrier Disruption for Potential Enhancement of Boron Delivery for Neutron Capture Therapy
AID  - 10.2967/jnumed.113.125716
DP  - 2014 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 616--621
VI  - 55
IP  - 4
4099  - http://jnm.snmjournals.org/content/55/4/616.short
4100  - http://jnm.snmjournals.org/content/55/4/616.full
SO  - J Nucl Med2014 Apr 01; 55
AB  - Boronophenylalanine has been applied in clinical boron neutron capture therapy for the treatment of high-grade gliomas. The purpose of this study was to evaluate the pharmacokinetics of 4-borono-2-18F-fluoro-l-phenylalanine-fructose (18F-FBPA-Fr) in F98 glioma–bearing Fischer 344 rats by means of intravenous injection of 18F-FBPA-Fr both with and without blood–brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). Methods: Dynamic PET imaging of 18F-FBPA-Fr was performed on the ninth day after tumor implantation. Blood samples were collected to obtain an arterial input function for tracer kinetic modeling. Ten animals were scanned for approximately 3 h to estimate the uptake of 18F radioactivity with respect to time for the pharmacokinetic analysis. Rate constants were calculated by use of a 3-compartment model. Results: The accumulation of 18F-FBPA-Fr in brain tumors and the tumor-to-contralateral brain ratio were significantly elevated after intravenous injection of 18F-FBPA-Fr with BBB-D. 18F-FBPA-Fr administration after sonication showed that the tumor-to-contralateral brain ratio for the sonicated tumors (3.5) was approximately 1.75-fold higher than that for the control tumors (2.0). Furthermore, the K1/k2 pharmacokinetic ratio after intravenous injection of 18F-FBPA-Fr with BBB-D was significantly higher than that after intravenous injection without BBB-D. Conclusion: This study demonstrated that radioactivity in tumors and the tumor-to-normal brain ratio after intravenous injection of 18F-FBPA-Fr with sonication were significantly higher than those in tumors without sonication. The K1/k2 ratio may be useful for indicating the degree of BBB-D induced by FUS. Further studies are needed to determine whether FUS may be useful for enhancing the delivery of boronophenylalanine in patients with high-grade gliomas.