A simplified one-pot synthesis of 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine ([18F]FH
- 作者：Shiue ; Grace G. ; Shiue ; Chyng-Yann ; Lee ; Roland L. ; MacDonald ; Douglas ; Hustinx ; Roland ; Eck ; Stephen L. ; et. al.
- 关键词：Gene therapy ; [18F]FHPG ; [18F]FHBG ; Ganciclovir ; Penciclovir ; Stability of [18F]FHPG
- 刊名：Nuclear Medicine and Biology
- 出版年：2001
- 期刊代码：43_09698051
- 类别：ph
- 出版时间：October, 2001
- 卷：28
- 期：7
- 页码：875-883
- 文件大小：1.34 M
摘要
9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG, 2) has been synthesized by nucleophilic substitution of N2-(p-anisyldiphenylmethyl)-9-{[1-(p-anisyldiphenylmethoxy)-3-toluenesulfonyloxy-2-propoxy]methyl}guanine (1) with potassium [18F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90°C and the product was purified by HPLC (method A), the yield of compound 2 was 5–10%and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120°C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90°C and purified by Silica Sep-Pak (method B), the yield increased to 10–15%and the synthesis time was 60 min from EOB. Similarly, 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG, 4) was synthesized with method A and method B in 9%and 10–15%yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120°C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126 ± 0.022, n=5 and 0.165 ± 0.023, n=5, respectively). Although it contains non-radioactive ganciclovir (
5–30 μg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains 10–25 μg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is readily amenable for automation.
5–30 μg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains 10–25 μg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is readily amenable for automation.