Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

2 Publications
18F-Labelling of a Potent Nonpeptide CCR1 Antagonist for the Diagnosis of the Alz-heimer’s Disease
Mäding, P.; Füchtner, F.; Hilger, C. S.; Halks-Miller, M.; Horuk, R.;
Objectives: PET imaging of cardiac reporter gene expression holds promise for noninvasive monitoring of gene therapy. Two approaches based on herpesviral thymidine kinase gene(HSV1-tk) habe been applied. Wild-type HSV1-tk was imaged with 2´-fluoro-2´-deoxy-5[124I]-iodo-arabinofuranosyluracil([124I]FIAU), and mutant HSV1-sr39tk was imaged with 9-[4-[18F]-fluoro-3-(hydroxymethylbutyl)guanine([18F]FHBG).
Methods: Adenovirus expressing wild-type HSV1-tk(Adtk), mutant HSV1-sr39tk (Adsr39tk), or control gene (AdLacZ) were directly injected into myocarcardium of 24 rats and 8 pigs. Two days later, dynamic PET imaging was performed for 120 min after injection of [124I]FIAU or [18F]FHBG with a clinical scanner. Imaging with [13N]-ammonia was performed to identify cardiac regions of interest. Pig hearts were sliced into 5 short-axis slices for ex vivo imaging, and regional tracer uptake was analyzed.
Results: For [124I]FIAU, the largest difference of cardiac uptake between Adtk rats and controls was found at 10-30 min after injection (1.7±0.25 vs 0.87±0.22 %dose/ml, p=0.035). No difference was observed at later imaging times due to [124I]FIAU washout. For [18F]FHBG, difference between Adsr39tk rats and controls continuously increased over time and was largest at 105-120 min (1.45±0.45 vs 0.35±0.05 %dose/ml, P=0.0066). Global cardiac reporter probe kinetics in rats was confirmed by regional myocardial analysis in pigs. Transgene expression was specifically visualized by both approaches. Highest target/background ratio of [124I]FIAU in Adtk infected myocardium was 1.50±0.20 vs 2.64±0.49 for [18F]FHBG in Adsr39tk infected areas (P=0.01). In vivo results of rats were confirmed by ex vivo counting and autoradiography. In vivo segmental reporter probe uptake in pigs correlated well with those in ex vivo images.
Conclusions: Both combinations were feasible for PET of cardiac transgene expression in different species. Specific probe kinetics suggests different myocardial handling of pyrimidine ([124I]FIAU) and acycloguanosine ([18F]FHBG) derivatives. Results are in favour of [18F]FHBG because of continuous accumulation over time and higher imaging contrast.
  • Lecture (Conference)
    12th Workshop of the Central European Division e. V. of the International Isotope Society, 17.-18.06.2004, Bad Soden, Germany
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 47(2004), 1053-1054

Publ.-Id: 6317 - Permalink