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-2-18 F-fluoro-L-phenylalanine-fructose ( 18 F-FBPA-Fr) in F98 gliomabearing Fischer 344 rats by means of intravenous injection of 18 F-FBPA-Fr both with and without blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). Methods: Dynamic PET imaging of 18 F-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 18 F radioactivity with respect to time for the pharmacokinetic analysis. Rate constants were calculated by use of a 3-compartment model. Results: The accumulation of 18 F-FBPA-Fr in brain tumors and the tumor-to-contralateral brain ratio were significantly elevated after intravenous injection of 18 F-FBPA-Fr with BBB-D. 18 F-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 K 1 /k 2 pharmacokinetic ratio after intravenous injection of 18 F-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 18 F-FBPA-Fr with sonication were significantly higher than those in tumors without sonication. The K 1 /k 2 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. Bor on neutron capture therapy (BNCT) is a binary cancer treatment system that requires the selective delivery of a boroncontaining drug to the tumor and then irradiation with neutrons to yield high-linear-energy-transfer a particles and recoiling 7 Li nuclei (1-5). Successful application of BNCT requires the selective delivery of 10 B to the tumor, low levels in the surrounding tissue, and the delivery of sufficient thermal neutron fluence to the tumor site (6,7). Considerable efforts have been dedicated to the development of boron-delivering agents that could ensure a high tumor-to-normal tissue ratio of uptake of boron in tumors for BNCT (8). With the development of new techniques for the chemical synthesis of an effective agent, several new potential boron-delivering agents have emerged. However, drug delivery will have to be optimized because it is unlikely that any single agent will be capable of targeting most of the tumor cells.Despite the fact that the blood-tumor barrier is more permeable than the blood-brain barrier (BBB), the efficacy of systemic chemotherapy in patients with brain tumors is poor because the selective permeability of the blood-tumor barrier st...
The ability to monitor the responses of and inhibit the growth of brain tumors during gene therapy has been severely limited due to the blood-brain barrier (BBB). A previous study has demonstrated the feasibility of noninvasive in vivo imaging with 123I-2′-fluoro-2′-deoxy-5-iodo-1-β-D-arabinofuranosyluracil (123I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here, we tested the enhancement of SPECT with 123I-FIAU and ganciclovir (GCV) treatment in brain tumors after BBB disruption induced by focused ultrasound (FUS) in the presence of microbubbles. We established an orthotopic F98 glioma-bearing rat model with trifusion reporter genes. The results of this study showed that the rat model of HSV1-tk-expressing glioma cells could be successfully detected by SPECT imaging after FUS-induced BBB disruption on day 10 after implantation. Compared to the control group, animals receiving the GCV with or without sonication exhibited a significant antitumor activity (P < 0.05) of glioma cells on day 16 after implantation. Moreover, combining sonication with GCV significantly inhibited tumor growth compared with GCV alone. This study demonstrated that FUS may be used to deliver a wide variety of theranostic agents to the brain for molecular imaging and gene therapy in brain diseases.
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