Evaluation of an automated double-synthesis module: efficiency and reliability of subsequent radiosyntheses of FHBG and FLT

被引:7
作者
Niedermoser, Sabrina [1 ]
Pape, Manuela [1 ]
Gildehaus, Franz Josef [1 ]
Waengler, Carmen [1 ]
Hartenbach, Markus [2 ]
Schirrmacher, Ralf [3 ]
Bartenstein, Peter [1 ]
Waengler, Bjoern [1 ,4 ]
机构
[1] Univ Munich, Dept Nucl Med, D-81377 Munich, Germany
[2] German Fed Armed Forces Hosp, Ulm, Germany
[3] McGill Univ, Cyclotron Radiochem Lab, McConnell Brain Imaging Ctr, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada
[4] Heidelberg Univ, Dept Clin Radiol & Nucl Med, Med Fac Mannheim, D-68167 Mannheim, Germany
关键词
F-18]FLT; F-18]FHBG; Double synthesis; Explora GN;
D O I
10.1016/j.nucmedbio.2011.10.018
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
We optimized the synthesis methods for 3'-deoxy-3-[F-18]fluorothymidine ([F-18]FLT) and 9-(4-[F-18]fluoro-3-[hydroxymethyl]butyl) guanine) ([F-18]FHBG) and automated them on an Explora General Nucleophilic double-synthesis module. Furthermore, the synthesis efficiency and reliability and the formation of cross-contaminations of the products when preparing two consecutive batches were evaluated. Whereas the preinstalled FLT synthesis conditions required substantial modification in reaction and neutralization conditions to achieve radiochemical yields of up to 60% within 70 +/- 10 min including high-performance liquid chromatography purification, the synthesis of FHBG had to be implemented to the module to obtain competitive radiochemical yields of up to 40% in an overall synthesis time of 60 +/- 10 min. The radiochemical purities obtained were >= 99% and >= 96% for the synthesis of[F-18]FLT and [F-18]FHBG, respectively. No significant changes in yield or purity could be observed between both batch productions. We found that the yields and purities also did not change when performing FLT after FHBG syntheses and vice versa. Hence, we developed a synthesis setup that offers the opportunity to perform two subsequent syntheses of either [F-18]FLT, [F-18]FHBG or [F-18]FLT after [F-18]FHBG without decrease in radiochemical yields and purities. Also, no cross-contaminations were observed, which can be attributed to the use of separate product delivery tubes, purification columns and an automated intermediate cleaning program. These results open up the possibility of producing consecutively either two equal F-18-fluorinated tracers or two different ones in high yields on the same synthesis module. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:586 / 592
页数:7
相关论文
共 13 条
[1]   Synthesis and preliminary evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG):: A new potential imaging agent for viral infection and gene therapy using PET [J].
Alauddin, MM ;
Conti, PS .
NUCLEAR MEDICINE AND BIOLOGY, 1998, 25 (03) :175-180
[2]  
Barthel H, 2003, CANCER RES, V63, P3791
[3]   Assays for noninvasive imaging of reporter gene expression [J].
Gambhir, SS ;
Barrio, JR ;
Herschman, HR ;
Phelps, ME .
NUCLEAR MEDICINE AND BIOLOGY, 1999, 26 (05) :481-490
[4]   Radiosynthesis of 3′-deoxy-3′-[18F]fluorothymidine:: [18F]FLT for imaging of cellular proliferation in vivo [J].
Grierson, JR ;
Shields, AF .
NUCLEAR MEDICINE AND BIOLOGY, 2000, 27 (02) :143-156
[5]   Comparison of two full automatic synthesis methods of 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine using different chemistry modules [J].
Kang, Se Hun ;
Oh, Seung Jun ;
Lee, Sang Ju ;
Kang, Keon Wook ;
Kim, Seok-ki ;
Lee, Ho-young ;
Lee, Sang Jin ;
Kim, In Hoo ;
Lee, Won Koo .
APPLIED RADIATION AND ISOTOPES, 2009, 67 (10) :1758-1763
[6]   A new class of SN2 reactions catalyzed by protic solvents:: Facile fluorination for isotopic labeling of diagnostic molecules [J].
Kim, Dong Wook ;
Ahn, Doo-Sik ;
Oh, Young-Ho ;
Lee, Sungyul ;
Kil, Hee Seup ;
Oh, Seung Jun ;
Lee, Sang Ju ;
Kim, Jae Seung ;
Ryu, Jin Sook ;
Moon, Dae Hyuk ;
Chi, Dae Yoon .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (50) :16394-16397
[7]   Simple and highly efficient synthesis of 3′-deoxy-3′-[18F]fluorothymidine using nucleophilic fluorination catalyzed by protic solvent [J].
Lee, Sang Ju ;
Oh, Seung Jun ;
Chi, Dae Yoon ;
Kil, Hee Seup ;
Kim, Euy Nyong ;
Ryu, Jin Sook ;
Moon, Dae Hyuk .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2007, 34 (09) :1406-1409
[8]   Fully automated synthesis system of 3′-deoxy-3′-[18F]fluorothymidine [J].
Oh, SJ ;
Mosdzianowski, C ;
Chi, DY ;
Kim, JY ;
Kang, SH ;
Ryu, JS ;
Yeo, JS ;
Moon, DH .
NUCLEAR MEDICINE AND BIOLOGY, 2004, 31 (06) :803-809
[9]  
Penuelas Ivan, 2002, Mol Imaging Biol, V4, P415, DOI 10.1016/S1536-1632(02)00086-0
[10]   A facile and rapid automated synthesis of 3′-deoxy-3′-[18F]fluorothymidine [J].
Tang, Ganghua ;
Tang, Xiaolan ;
Wen, Fuhua ;
Wang, Mingfang ;
Li, Baoyuan .
APPLIED RADIATION AND ISOTOPES, 2010, 68 (09) :1734-1739