Reference : A simplified one-pot synthesis of 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([...
Scientific journals : Article
Human health sciences : Radiology, nuclear medicine & imaging
http://hdl.handle.net/2268/18894
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]FHBG) for gene therapy.
English
Shiue, Grace G. [University of Pennsylvania > Department of Radiology > > >]
Shiue, Ching-Yann [University of Pennsylvania > Department of Radiology > > >]
Lee, Roland L. [University of Pennsylvania > Department of Radiology > > >]
MacDonald, Douglas [University of Pennsylvania > Department of Chemistry > > >]
Hustinx, Roland mailto [Université de Liège - ULg > Département des sciences cliniques > Médecine nucléaire >]
Eck, Stephen L. [University of Pennsylvania > Department of Mediciine > > >]
Alavi, Abass [University of Pennsylvania > Department of Radiology > > >]
2001
Nuclear Medicine & Biology
Pergamon Press
28
7
875-83
Yes (verified by ORBi)
International
0969-8051
Oxford
United Kingdom
[en] Chemistry, Physical ; Chromatography, High Pressure Liquid ; Ganciclovir/analogs & derivatives/chemical synthesis/chemistry/metabolism/pharmacology ; Gene Therapy ; Genetic Vectors ; Glioma/metabolism ; Guanine/analogs & derivatives/chemical synthesis/chemistry/metabolism ; Herpesvirus 1, Human/genetics ; Humans ; Physicochemical Phenomena ; Radiopharmaceuticals/chemical synthesis/chemistry/metabolism ; Spectrophotometry, Ultraviolet ; Thymidylate Synthase/genetics ; Tumor Cells, Cultured
[en] 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG, 2) has been synthesized by nucleophilic substitution of N(2)-(p-anisyldiphenylmethyl)-9-[[1-(p-anisyldiphenylmethoxy)-3-toluenesulfonylox y-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 degrees 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 degrees C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 degrees 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 degrees 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 ( approximately 5-30 microg) 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 approximately 10-25 microg 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.
http://hdl.handle.net/2268/18894

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