Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression

被引:68
作者
Brust, P
Haubner, R
Friedrich, A
Scheunemann, M
Anton, M
Koufaki, ON
Hauses, M
Noll, S
Noll, B
Haberkorn, U
Schackert, G
Schackert, HK
Avril, N
Johannsen, B
机构
[1] Tech Univ Munich, Dept Nucl Med, D-81675 Munich, Germany
[2] Forschungszentrum, Inst Bioinorgan & Radiopharmaceut Chem, Rossendorf, Germany
[3] Tech Univ Munich, Inst Expt Oncol, Munich, Germany
[4] Tech Univ Dresden, Dept Surg Res, Dresden, Germany
[5] Deutsch Krebsforschungszentrum, Dept Oncol Diagnost & Therapy, D-6900 Heidelberg, Germany
[6] Tech Univ Dresden, Dept Neurosurg, Dresden, Germany
关键词
gene therapy; FHPG; FIAU; HSV-1; thymidine kinase; positron emission tomography;
D O I
10.1007/s002590100526
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
Various radiotracers based on uracil nucleosides (e,g, [I-124]2 ' -fluoro-2 ' -deoxy-5-iodo-1-beta -D-arabinofuranosyluracil, [I-124]FIAU) and acycloguanosine derivatives (e.g. [F-18]9-[(3-fluoro-1-hydroxy-2-propoxy)methyl] guanine, [F-18]FHPG) have been proposed for the non-invasive imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene expression. However, these radiotracers have been evaluated in different in vitro and in vivo models, precluding a direct comparison. Therefore, we directly compared [F-18]FHPG and radioiodinated FIAU to assess their potential for PET imaging of transgene expression. The uptake of [I-125]FIAU, [F-18]FHPG and [H-3]acyclovir was determined in vitro using four different HSV1-tk expressing cell lines and their respective negative controls. The in vitro tracer uptake was generally low in non-transduced parental cell lines, In HSV1-tk expressing cells, [H-3]acyclovir showed approximately a twofold higher tracer accumulation, the [F-18]FHPG uptake increased by about sixfold and the ["SI]FIAU accumulation increased by about 28-fold after 120-min incubation of T1115 human glioblastoma cells. Similar results were found in the other cell lines, In addition, biodistribution and positron emission tomography (PET) studies with [F-18]FHPG and [I-124/125]FIAU were carried out in tumour-bearing BALB/c mice. Significantly higher specific accumulation of radioactivity was found for [I-125]FIAU compared with [F-18]FHPG. The ratio of specific tracer accumulation between [I-125]FIAU and [F-18]FHPG increased from 21 (30 min p.i.) to 119 (4 h p.i.), PET imaging, using [I-124]FIAU, clearly visualised and delineated HSV1-rk expressing tumours, whereas only a negligible uptake of [F-18]FHPG was observed, This study demonstrated that in vitro and in vivo, the radioiodinated uracil nucleoside FIAU has a significantly higher specific accumulation than the acycloguanosine derivative [F-18]FHPG. This suggests that [I-124]FIAU should be the preferred reporter probe for PET imaging of HSV1-tk gene expression, Thus, further attempts to develop suitable PET tracers for the assessment of HSV1-tk gene expression should also focus on F-18-labelled uracil derivatives.
引用
收藏
页码:721 / 729
页数:9
相关论文
共 32 条
[11]   Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography [J].
Gambhir, SS ;
Barrio, JR ;
Phelps, ME ;
Iyer, M ;
Namavari, M ;
Satyamurthy, N ;
Wu, L ;
Green, LA ;
Bauer, E ;
MacLaren, DC ;
Nguyen, K ;
Berk, AJ ;
Cherry, SR ;
Herschman, HR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (05) :2333-2338
[12]   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
[13]  
Haberkorn U, 1997, J NUCL MED, V38, P1048
[14]   Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex virus thymidine kinase [J].
Haberkorn, U ;
Khazaie, K ;
Morr, I ;
Altmann, A ;
Muller, M ;
van Kaick, G .
NUCLEAR MEDICINE AND BIOLOGY, 1998, 25 (04) :367-373
[15]  
Haberkorn U, 1997, J NUCL MED, V38, P287
[16]   In vivo imaging of herpes simplex virus type 1 thymidine kinase gene expression: early kinetics of radiolabelled FIAU [J].
Haubner, R ;
Avril, N ;
Hantzopoulos, PA ;
Gansbacher, B ;
Schwaiger, M .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE, 2000, 27 (03) :283-291
[17]  
Hospers GAP, 2000, CANCER RES, V60, P1488
[18]   ENZYMATIC PHOSPHORYLATION OF ACYCLIC NUCLEOSIDE ANALOGS AND CORRELATIONS WITH ANTIHERPETIC ACTIVITIES [J].
KELLER, PM ;
FYFE, JA ;
BEAUCHAMP, L ;
LUBBERS, CM ;
FURMAN, PA ;
SCHAEFFER, HJ ;
ELION, GB .
BIOCHEMICAL PHARMACOLOGY, 1981, 30 (22) :3071-3077
[19]   Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals [J].
MacLaren, DC ;
Gambhir, SS ;
Satyamurthy, N ;
Barrio, JR ;
Sharfstein, S ;
Toyokuni, T ;
Wu, L ;
Berk, AJ ;
Cherry, SR ;
Phelps, ME ;
Herschman, HR .
GENE THERAPY, 1999, 6 (05) :785-791
[20]   PET imaging of transgene expression [J].
MacLaren, DC ;
Toyokuni, T ;
Cherry, SR ;
Barrio, JR ;
Phelps, ME ;
Herschman, HR ;
Gambhir, SS .
BIOLOGICAL PSYCHIATRY, 2000, 48 (05) :337-348