Evaluation of 4-borono-2-18F-fluoro-L-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model

Hsin Ell Wang, Ai Ho Liao, Win Ping Deng, Pi Fang Chang, Jyh Cheng Chen, Fu Du Chen, Ren Shen Liu, Jin Shin Lee, Jeng Jong Hwang

研究成果: 雜誌貢獻文章

35 引文 (Scopus)

摘要

L-p-Boronophenylalanine (BPA) has been applied as a potential boron carrier for the treatment of malignant glioma in clinical boron neutron capture therapy (BNCT) since 1994. To provide the pharmacokinetics of BPA for clinical use of BNCT in Taiwan, 4-borono-2-18F-fluoro-L-phenylalanine-fructose ( 18F-FBPA-Fr) was synthesized and the biologic characteristics of this radiotracer in glioma-bearing rats were investigated. Methods: Radiolabeled 18F-F2 was produced via the 20Ne(d,α) 18F reaction, and 18F-acetyl hypofluorite ( 18F-AcOF) was generated by passing 18F-F2 through a column filled with tightly packed KOAc/HOAc powder. The effluent containing 18F-AcOF was bubbled into BPA in trifluoroacetic acid, then purified by high-performance liquid chromatography, and further composited with fructose to afford 18F-FBPA-Fr. Male Fischer 344 rats bearing F98 glioma in the left brain were used for biologic studies. The biodistribution of BPA-Fr and 18F-FBPA-Fr was determined, and the microautoradiography and PET imaging of 18F-FBPA-Fr were performed, on the 13th day after tumor inoculation. Results: The radiochemical purity of 18F-FBPA-Fr was >97% and the radiochemical yield of 18F-FBPA-Fr was 20%-25%. In glioma-bearing rats, the accumulation ratios of B-10 for glioma-to-normal brain were 2.05, 1.86, 1.24, and 1.10 at 0.5, 1, 2, and 4 h, respectively, after administration of 43 mg BPA-Fr via the tail vein. The accumulation ratios of 18F-FBPA-Fr for glioma-to-normal brain were 3.45, 3.13, 2.61, and 2.02, whereas the tumor-to-heart blood ratios were 1.72, 2.61, 2.00, and 1.93, respectively, for the same time points. The uptake characteristics of BPA-Fr and 18F-FBPA-Fr in F98 glioma were similar with a maximum at 1 h after the drugs' administration. The results obtained from the biodistribution studies indicated that 0.5-1 h after BPA-Fr injection would be the optimal time for BNCT. Biodistribution, PET images, and brain microautoradiography of 18F-FBPA-Fr all confirmed this finding. Conclusion: 18F-FBPA-Fr showed specific tumor uptake in F98 glioma-bearing rats and could be used as a probe for BPA-Fr in BNCT. This study provides useful information for the future clinical application of BNCT in brain tumor therapy.

原文英語
頁(從 - 到)302-308
頁數7
期刊Journal of Nuclear Medicine
45
發行號2
出版狀態已發佈 - 二月 1 2004

指紋

Boron Neutron Capture Therapy
Glioma
Brain
Trifluoroacetic Acid
Heart Neoplasms
Boron
4-borono-2-fluorophenylalaninefructose
Inbred F344 Rats
Fructose
Taiwan
Brain Neoplasms
Powders
Tail
Veins
Neoplasms
Pharmacokinetics
High Pressure Liquid Chromatography
Injections

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

引用此文

Evaluation of 4-borono-2-18F-fluoro-L-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model. / Wang, Hsin Ell; Liao, Ai Ho; Deng, Win Ping; Chang, Pi Fang; Chen, Jyh Cheng; Chen, Fu Du; Liu, Ren Shen; Lee, Jin Shin; Hwang, Jeng Jong.

於: Journal of Nuclear Medicine, 卷 45, 編號 2, 01.02.2004, p. 302-308.

研究成果: 雜誌貢獻文章

Wang, HE, Liao, AH, Deng, WP, Chang, PF, Chen, JC, Chen, FD, Liu, RS, Lee, JS & Hwang, JJ 2004, 'Evaluation of 4-borono-2-18F-fluoro-L-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model', Journal of Nuclear Medicine, 卷 45, 編號 2, 頁 302-308.
Wang, Hsin Ell ; Liao, Ai Ho ; Deng, Win Ping ; Chang, Pi Fang ; Chen, Jyh Cheng ; Chen, Fu Du ; Liu, Ren Shen ; Lee, Jin Shin ; Hwang, Jeng Jong. / Evaluation of 4-borono-2-18F-fluoro-L-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model. 於: Journal of Nuclear Medicine. 2004 ; 卷 45, 編號 2. 頁 302-308.
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title = "Evaluation of 4-borono-2-18F-fluoro-L-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model",
abstract = "L-p-Boronophenylalanine (BPA) has been applied as a potential boron carrier for the treatment of malignant glioma in clinical boron neutron capture therapy (BNCT) since 1994. To provide the pharmacokinetics of BPA for clinical use of BNCT in Taiwan, 4-borono-2-18F-fluoro-L-phenylalanine-fructose ( 18F-FBPA-Fr) was synthesized and the biologic characteristics of this radiotracer in glioma-bearing rats were investigated. Methods: Radiolabeled 18F-F2 was produced via the 20Ne(d,α) 18F reaction, and 18F-acetyl hypofluorite ( 18F-AcOF) was generated by passing 18F-F2 through a column filled with tightly packed KOAc/HOAc powder. The effluent containing 18F-AcOF was bubbled into BPA in trifluoroacetic acid, then purified by high-performance liquid chromatography, and further composited with fructose to afford 18F-FBPA-Fr. Male Fischer 344 rats bearing F98 glioma in the left brain were used for biologic studies. The biodistribution of BPA-Fr and 18F-FBPA-Fr was determined, and the microautoradiography and PET imaging of 18F-FBPA-Fr were performed, on the 13th day after tumor inoculation. Results: The radiochemical purity of 18F-FBPA-Fr was >97{\%} and the radiochemical yield of 18F-FBPA-Fr was 20{\%}-25{\%}. In glioma-bearing rats, the accumulation ratios of B-10 for glioma-to-normal brain were 2.05, 1.86, 1.24, and 1.10 at 0.5, 1, 2, and 4 h, respectively, after administration of 43 mg BPA-Fr via the tail vein. The accumulation ratios of 18F-FBPA-Fr for glioma-to-normal brain were 3.45, 3.13, 2.61, and 2.02, whereas the tumor-to-heart blood ratios were 1.72, 2.61, 2.00, and 1.93, respectively, for the same time points. The uptake characteristics of BPA-Fr and 18F-FBPA-Fr in F98 glioma were similar with a maximum at 1 h after the drugs' administration. The results obtained from the biodistribution studies indicated that 0.5-1 h after BPA-Fr injection would be the optimal time for BNCT. Biodistribution, PET images, and brain microautoradiography of 18F-FBPA-Fr all confirmed this finding. Conclusion: 18F-FBPA-Fr showed specific tumor uptake in F98 glioma-bearing rats and could be used as a probe for BPA-Fr in BNCT. This study provides useful information for the future clinical application of BNCT in brain tumor therapy.",
keywords = "4-borono-2-F-fluoro-L- phenylalanine-fructose, Boron neutron capture therapy, F98 glioma, Microautoradiography, PET",
author = "Wang, {Hsin Ell} and Liao, {Ai Ho} and Deng, {Win Ping} and Chang, {Pi Fang} and Chen, {Jyh Cheng} and Chen, {Fu Du} and Liu, {Ren Shen} and Lee, {Jin Shin} and Hwang, {Jeng Jong}",
year = "2004",
month = "2",
day = "1",
language = "English",
volume = "45",
pages = "302--308",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "2",

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TY - JOUR

T1 - Evaluation of 4-borono-2-18F-fluoro-L-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model

AU - Wang, Hsin Ell

AU - Liao, Ai Ho

AU - Deng, Win Ping

AU - Chang, Pi Fang

AU - Chen, Jyh Cheng

AU - Chen, Fu Du

AU - Liu, Ren Shen

AU - Lee, Jin Shin

AU - Hwang, Jeng Jong

PY - 2004/2/1

Y1 - 2004/2/1

N2 - L-p-Boronophenylalanine (BPA) has been applied as a potential boron carrier for the treatment of malignant glioma in clinical boron neutron capture therapy (BNCT) since 1994. To provide the pharmacokinetics of BPA for clinical use of BNCT in Taiwan, 4-borono-2-18F-fluoro-L-phenylalanine-fructose ( 18F-FBPA-Fr) was synthesized and the biologic characteristics of this radiotracer in glioma-bearing rats were investigated. Methods: Radiolabeled 18F-F2 was produced via the 20Ne(d,α) 18F reaction, and 18F-acetyl hypofluorite ( 18F-AcOF) was generated by passing 18F-F2 through a column filled with tightly packed KOAc/HOAc powder. The effluent containing 18F-AcOF was bubbled into BPA in trifluoroacetic acid, then purified by high-performance liquid chromatography, and further composited with fructose to afford 18F-FBPA-Fr. Male Fischer 344 rats bearing F98 glioma in the left brain were used for biologic studies. The biodistribution of BPA-Fr and 18F-FBPA-Fr was determined, and the microautoradiography and PET imaging of 18F-FBPA-Fr were performed, on the 13th day after tumor inoculation. Results: The radiochemical purity of 18F-FBPA-Fr was >97% and the radiochemical yield of 18F-FBPA-Fr was 20%-25%. In glioma-bearing rats, the accumulation ratios of B-10 for glioma-to-normal brain were 2.05, 1.86, 1.24, and 1.10 at 0.5, 1, 2, and 4 h, respectively, after administration of 43 mg BPA-Fr via the tail vein. The accumulation ratios of 18F-FBPA-Fr for glioma-to-normal brain were 3.45, 3.13, 2.61, and 2.02, whereas the tumor-to-heart blood ratios were 1.72, 2.61, 2.00, and 1.93, respectively, for the same time points. The uptake characteristics of BPA-Fr and 18F-FBPA-Fr in F98 glioma were similar with a maximum at 1 h after the drugs' administration. The results obtained from the biodistribution studies indicated that 0.5-1 h after BPA-Fr injection would be the optimal time for BNCT. Biodistribution, PET images, and brain microautoradiography of 18F-FBPA-Fr all confirmed this finding. Conclusion: 18F-FBPA-Fr showed specific tumor uptake in F98 glioma-bearing rats and could be used as a probe for BPA-Fr in BNCT. This study provides useful information for the future clinical application of BNCT in brain tumor therapy.

AB - L-p-Boronophenylalanine (BPA) has been applied as a potential boron carrier for the treatment of malignant glioma in clinical boron neutron capture therapy (BNCT) since 1994. To provide the pharmacokinetics of BPA for clinical use of BNCT in Taiwan, 4-borono-2-18F-fluoro-L-phenylalanine-fructose ( 18F-FBPA-Fr) was synthesized and the biologic characteristics of this radiotracer in glioma-bearing rats were investigated. Methods: Radiolabeled 18F-F2 was produced via the 20Ne(d,α) 18F reaction, and 18F-acetyl hypofluorite ( 18F-AcOF) was generated by passing 18F-F2 through a column filled with tightly packed KOAc/HOAc powder. The effluent containing 18F-AcOF was bubbled into BPA in trifluoroacetic acid, then purified by high-performance liquid chromatography, and further composited with fructose to afford 18F-FBPA-Fr. Male Fischer 344 rats bearing F98 glioma in the left brain were used for biologic studies. The biodistribution of BPA-Fr and 18F-FBPA-Fr was determined, and the microautoradiography and PET imaging of 18F-FBPA-Fr were performed, on the 13th day after tumor inoculation. Results: The radiochemical purity of 18F-FBPA-Fr was >97% and the radiochemical yield of 18F-FBPA-Fr was 20%-25%. In glioma-bearing rats, the accumulation ratios of B-10 for glioma-to-normal brain were 2.05, 1.86, 1.24, and 1.10 at 0.5, 1, 2, and 4 h, respectively, after administration of 43 mg BPA-Fr via the tail vein. The accumulation ratios of 18F-FBPA-Fr for glioma-to-normal brain were 3.45, 3.13, 2.61, and 2.02, whereas the tumor-to-heart blood ratios were 1.72, 2.61, 2.00, and 1.93, respectively, for the same time points. The uptake characteristics of BPA-Fr and 18F-FBPA-Fr in F98 glioma were similar with a maximum at 1 h after the drugs' administration. The results obtained from the biodistribution studies indicated that 0.5-1 h after BPA-Fr injection would be the optimal time for BNCT. Biodistribution, PET images, and brain microautoradiography of 18F-FBPA-Fr all confirmed this finding. Conclusion: 18F-FBPA-Fr showed specific tumor uptake in F98 glioma-bearing rats and could be used as a probe for BPA-Fr in BNCT. This study provides useful information for the future clinical application of BNCT in brain tumor therapy.

KW - 4-borono-2-F-fluoro-L- phenylalanine-fructose

KW - Boron neutron capture therapy

KW - F98 glioma

KW - Microautoradiography

KW - PET

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JO - Journal of Nuclear Medicine

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