1. Alveolar Echinococcosis metabolic imaging: from in vitro testing to small Animal Positron Emission Tomography
Porot C, Knapp J, Wang J, Camporese D, Germain S, Boulahdour H, Seimbille Y, Gottstein B, Vuitton D.A, Blagosklonov O
Department of Nuclear medicine, University of Franche-Comté and University hospital ,
University of Franche-Comté and University hospital, Besançon, France
WHO collaborating centre for prevention and treatment of human echinococcosis, Besançon, France
Advanced Accelerator Applications, St-Genis-Pouilly, France
University and University Hospitals of Geneva, Switzerland
IME-2014 – The 27th of March 2014

2. BACKGROUND 18F D-glucose OH HO O 18F-FDG OH HO O
Usefulness of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography ([18F]-FDG-PET) for detection of inflammatory and infectious lesions well known
[18F]-FDG-PET can be used for assessment of peri-parasite immune response [1-2]
 reflecting indirectly the parasitic activity
[18F]-FDG is still a non specific tracer of AE activity
[1] S. Reuter, H. Schirrmeister, W. Kratzer, C. Dreweck, S. N. Reske, andP. Kern,“Pericystic metabolic activity in alveolar echinococcosis:assessment and follow-up by positron emission tomography”, Clin.Infect .Dis, vol 29 pp , Nov
[2] C. Caoduro, C. Porot, D. A. Vuitton, S. Bresson-Hadni, F. Grenouillet, C. Richou, H. Boulahdour, et O. Blagosklonov, « The role of delayed 18F-FDG PET imaging in the follow-up of patients with alveolar echinococcosis », J. Nucl. Med., vol. 54, no 3, p. 358‑363, mars 2013.
D-glucose OH HO O
18F-FDG OH HO O
18F

3. BACKGROUND / AIMS IsotopEchino :
project of 815’972€ which lasted 3 years (ending 31/03/2014), supported by the INTERREG IV program between France and Switzerland
aims to a better understanding of the metabolic uptake of [18F]-FDG by AE lesions (cellular target)
aims to develop new radiotracer, more specific for PET imaging of AE  improve detection, clinical monitoring, and the management of treatment of alveolar echinococcosis

4. STEPS OF THE STUDY
I- Design of the in vitro radio-labelling protocole II- In vitro comparison of the uptake of FDG and other candidates tracers by the different types of cells (host & parasite) involved in the host parasite interface of AE  Better understand the FDG target in AE lesions  Try to select a specific tracer III- In vivo experiments in a dedicated murine model

5. IN VITRO ASSAYS Assays for the uptake of other fluorinated tracers:
Design of transversal radiolabelling process for all the tracers
Assays for the uptake of FDG in 3 targets:
h WBCs
h Hepatocytes
E.m vesicles
Assays for the uptake of other fluorinated tracers:
[18F]-fluorotyrosine (FET)
[18F]-fluorothymidine (FLT)
[18F]-fluorométhylcholine (FMC)
sodium [18F]- fluorine (NaF)
N.B: same targets
Each experiment, for each molecule, was performed on 3 independent pools
Main parameter assessed: mean radiolabelling efficiency (%)

6. IN VIVO ASSAYS
Design of a dedicated murine model by the Institute of Parasitology of Berne for in vivo experiments
Wild-type mice were inoculated orally and by intraperiteonal injection of E. multilocularis metacestodes
FDG-PET scans performed 3 months later, using Triumph PET/SPECT/CT system (Gamma Medica, Inc., CA, USA).
PET images acquired during 1h after retro-orbital i.v. injection of 11.7 MBq of FDG and FLT
Experimental mice necropsied 1 day after FDG-PET scan

7. RESULTS – In vitro TRACERS TYPE OF CELLS E.m. vesicles 31.05% 92.89%
[18F]-FDG
[18F]-FLT
[18F]-FET
[18F]-FMC
[18F]-NaF
E.m. vesicles
31.05%
92.89%
43.15%
49.23% 0%
Human WBCs
52%
5.55%
56%
43.76%
Human hepatocytes
 4.47%
2.82%
1.02% 
45.8 % 
0.34% 

8. RESULTS – In vivo Fused images PET-CT scans
3 months after i.p. infection
FDG - PET
Necropsy

9. Conclusion Perspectives
Validated radiolabelling technique for fluorinated tracers
[18F]-FDG in vitro uptake: h WBC’s metabolism
[18F]-FLT = E.m. vesicles specific
In vivo experimental study in mice infected by AE ≠ in vitro study
Perspectives
Mini-pig model  More suitable for experimental study of PET tracers for human AE imaging?
Labelling of more specific molecules (mini-bodies?)

10. Thank you for your attention