Pharmacokinetic Analysis and Uptake of 18F-FBPA-Fr After Ultrasound-Induced Blood–Brain Barrier Disruption for Potential Enhancement of Boron Delivery for Neutron Capture Therapy

Journal of Nuclear Medicine

Jyh-Cheng Chen¹  Feng-Yi Yang¹  Hsin-Ell Wang¹  Chi-Wei Chang¹  Jia-Je Li¹  Wen-Yuan Chang¹ 

关键词: pharmacokinetics;    focused ultrasound;    blood–brain barrier;    ¹⁸F-FBPA-Fr;    boron neutron capture therapy;   

DOI  :  10.2967/jnumed.113.125716

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown