1. Applications of the CXS to Cancer Medicine E.C. Landahl, J. Boggan, W. Frederick, N.C. Luhmann, Jr. Departments of Applied Science and Electrical and Computer Engineering, University of California, Davis D. Matthews Medical Technologies Program, Lawrence Livermore National Laboratory V. Cooper, K. Iwamoto, A. Norman, T. Solberg Departments of Radiation Oncology and Biomedical Physics, University of California Los Angeles Improvements in Image Receptors Motivate Smaller X-Ray Source Sizes U T is the total unsharpness F is the intrinsic receptor unsharpness m is the magnification a is the source size a / F = 4 (large source) a / F = 2 a / F = 1 a / F = 0 (small source) Conventional New Compton X-Ray Source Contrast as Well as Spatial Resolution is Important for Radiography Source: NIST After S. Webb, The Physics of Medical Imaging 10 203040 50 Energy (keV) Contrast relative tonormal breast tissue.001.01.1 1 0.1 mm calcification 1 mm glandular tissue Contrast decreases rapidly with photon energy Low energy means a high patient dose Ideally, energy would be tuned to reach a desired contrast Application of the Compton X-Ray Source to Mammography SNR = 5  en /  = 0.439 cm 2 /g  = 3.6 mm -1 R = 200% E x = 20 keV  = 30% T = 20 cm A = 100 cm 2 100 mm calcification 1.2 mGy is a typical dose for a cranio-caudad projection CXS-1000 Flux Dose and Contrast for Radiography 11 22 T x For a given target dimension x, what dose is needed to achieve the desired contrast? R is the ratio of scattered to primary radiation, SNR is the desired Signal-to-Noise ratio,  is the detector efficiency, and N/A is the number of photons per unit area

2. Non-invasive Molecular Cancer Treatment Utilizing the CXS in Combination with Targeting Agents Cisplatin-DNA adduct Non-repairable damage Cell death Non-repairable damage Cell death Cisplatin-DNA adduct Repair Radiation Induced Single Strand Break If contrast agents can be introduced into sub-cellular regions, the x-ray energy could be tuned closer to the absorption edge, reducing the range of the radiation byproducts so that they are densely ionizing and more likely to create DNA double strand breaks In X-Ray Phototherapy, sparsely ionizing x-rays are selectively absorbed by high Z atoms which are likely localized in extracellular regions near target cells. In conventional external beam radiation therapy, sparsely ionizing x-rays pass through a target cell, only occasionally depositing energy CXS Chemoradiotherapy. Left: Cisplatin-DNA adducts (green) and radiation-induced single- strand breaks (red) in close proximity result in non- repairable damage and cell death. Right: CXS x- rays (red arrow) tuned to the Pt absorption edge are absorbed in proximity to the adduct and deposit radiation byproducts (orange) creating nearby single strand breaks and increasing likelihood of non repairable damage and cell death. X-Ray Phototherapy for Integrated Targeted Cancer Diagnosis and Treatment Before Treatment During Treatment After Treatment Dose to Tumor is Doubled Dose to Bone is Halved 4X Increase in Therapeutic Ratio from Monoenergeti c X-Rays Conventional 10 MV Radiation Therapy Polyenergetic X- Ray Phototherapy Results of UIP Monoenergetic X-Ray Phototherapy Study Calculated Dose Enhancement Factors (DEF) show wide variation over the energy distributions of conventional x- ray devices Data taken at APS December 2001 shows contrast media has anticipated PC3 cell kill in conjunction with 60 keV monoenergetic x-rays Large errors due to the difficulties of using synchrotrons for this type of research  CXS will be used for this type of research in the future XPT Simultaneous Imaging and Treatment of Canine Brain Tumors Advanced Treatment Methods CXS monoenergetic x-rays Tumor cell Chimeric promoter/ cytotoxic gene Heavy metal containing targeting agent Induced Gene Expression Unique radiation responses to targeted sub-cellular X-Ray Phototherapy may be a new parameter to adjust during radiation therapy Specific x-ray energy / contrast agent combinations may alter patient response to treatment based upon a pre- determined molecular cancer profile X-Ray Phototherapy radiation inducible promoters for gene therapy could have improved targeting or efficiency over existing promoters Advanced agents may incorporate a resonant x-ray triggered conformation change to deliver chemotherapeutics only upon external activation