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Animal Imaging: CF Gene Therapy

Animal Imaging: CF Gene Therapy. Zhenghong Lee, Ph.D. Departments of Radiology, Biomedical Engineering, and General medical Science Case Western Reserve University Cleveland, OH 44106. Acknowledgement. CF Center (CWRU) AG Ziady, Ph.D. PB Davis, M.D., Ph.D. Radiology/BME (CWRU)

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Animal Imaging: CF Gene Therapy

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

  2. Acknowledgement CF Center (CWRU) AG Ziady, Ph.D. PB Davis, M.D., Ph.D. Radiology/BME (CWRU) GR Wojtkiewicz JJ Derakshan PF Martone M Kotlarchyk Univ. of Virginia Dongfeng Pan, Ph.D. JLab (DOE) S. Majewski, Ph.D. D. Weisenberger, 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 Image Autoradiograph -IMAGER

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

  9. CF Study: Validation

  10. Reporter Gene Suicide gene: HSV1-tk HSV1-tk (gene) HSV1-TK (enzyme) Ganciclovir (GCV) GCV-PO4 (cellular enzymes) di/tri-PO4 Reporter gene: HSV1-tk Reporter gene probe: GCV

  11. Reporter Gene for Imaging (Imagene) Reporter gene: HSV1-tk HSV1-tk (gene) HSV1-TK (enzyme) [125I]FIAU FIAU-PO4 (cellular enzymes) di/tri-PO4 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. 125I-FIAU Injection to Image Stable HSV1-tk Complexes Artifacts De-halogenation

  16. HPLC Assay: [125I]-FIAU -trace 59.0 0.0 19.028

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

  18. 125I-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) saline tk (compated)

  22. CF Studies: uPET Imaging (UCLA)

  23. Two Concepts

  24. Imaging Modalities

  25. PET/SPECT Radio-nuclides

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