1. Animal Imaging: CF Gene Therapy Departments of Radiology, Biomedical Engineering, and General medical Science Case Western Reserve University Cleveland, OH 44106 Zhenghong Lee, Ph.D.

2. Acknowledgement CF Center (CWRU) AG Ziady, Ph.D. PB Davis, M.D., Ph.D. JLab (DOE) S. Majewski, Ph.D. D. Weisenberger, Ph.D. Radiology/BME (CWRU) GR Wojtkiewicz JJ Derakshan PF Martone M Kotlarchyk Univ. of Virginia Dongfeng Pan, Ph.D. UCLA H. Herschman, Ph.D. Q. Liang, Ph.D.

3. Molecular/Small Animal Imaging

4. Planar Multimodal Imaging System Small animal scanner, developed by JLab at CWRU/UHC, combining x-ray and scintigraphy

5. CF Gene Therapy Measurement

6. CF Studies: Gene Therapy

7. CF Studies: First Imaging  -IMAGER ImageAutoradiograph

8. CF Studies: Separate Imaging Small animal imager with a high sensitivity copper collimator Control with NaITargeted delivery

9. CF Study: Validation

10. Reporter Gene Suicide gene: HSV1-tk HSV1-tk (gene) HSV1-TK (enzyme) Ganciclovir (GCV) GCV-PO 4 (cellular enzymes) di/tri-PO 4 Reporter gene: HSV1-tk Reporter gene probe: GCV

11. Reporter Gene for Imaging (Imagene) Reporter gene: HSV1-tk HSV1-tk (gene) HSV1-TK (enzyme) [ 125 I]FIAU FIAU-PO 4 (cellular enzymes) di/tri-PO 4 Radiolabeled FIAU or other probes trapped to image reporter gene expression in vivo

12. TdR Analogues as Probe for HSV1-tk Expression 2’-fluoro-2’-deoxy-1-  -arabinofuranosyl-5-[I-125]-iodouracil (FIAU)

13. CF Studies: Multimodal Imaging Dual modality imaging

14. CF Studies: Multimodal Imaging Breathing mouse during imaging

15. 125 I-FIAU Injection to Image Stable HSV1-tk Complexes Artifacts De-halogenation

16. HPLC Assay: [ 125 I]-FIAU  -trace 0.019.028 59.0

17. X-ray detector uniformity correction Blocking thyroid uptake Imaging with Corrections

18. 125 I-FIAU Injection to Image Stable HSV1-tk Complexes

19. Furture Plans Multimodality Imaging for CF Gene Therapy Bioluminescent Imaging of Luc Cancer Imaging Projects Peptide Ligand (none-RGD) for angiogenesis Imaging Inflammatory Response Fab targeting neutrophils

20. Acknowledgement Whitaker Foundation Imaging grant (RG-00-0305) Cystic Fibrosis Foundation RDP grant (R477) Department of Energy/JLab Subcontract (DE/SURA-04-Q011)

21. CF Studies: uPET Imaging (UCLA) tk + luc (compacted)salinetk (compated)

22. CF Studies: uPET Imaging (UCLA)

23. Two Concepts

24. Imaging Modalities

25. PET/SPECT Radio-nuclides