Animal Imaging: CF Gene Therapy Departments of Radiology, Biomedical Engineering, and General medical Science Case Western Reserve University Cleveland,

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Presentation transcript:

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

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.

Molecular/Small Animal Imaging

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

CF Gene Therapy Measurement

CF Studies: Gene Therapy

CF Studies: First Imaging  -IMAGER ImageAutoradiograph

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

CF Study: Validation

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

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

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

CF Studies: Multimodal Imaging Dual modality imaging

CF Studies: Multimodal Imaging Breathing mouse during imaging

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

HPLC Assay: [ 125 I]-FIAU  -trace

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

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

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

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

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

CF Studies: uPET Imaging (UCLA)

Two Concepts

Imaging Modalities

PET/SPECT Radio-nuclides