Resonant Spectroscopy for Cancer Diagnosis and Therapy

“Resonant Spectroscopy Oncology Group”

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* For those free of cancer at beginning of age interval. Based on cancer cases diagnosed during 2000 to 2002.

Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0 Statistical Research and Applications Branch, NCI, 2005. http://srab.cancer.gov/devcan

Lifetime Probability of Developing Cancer, by Site, Men, 2000-2002*

Site Risk

All sites† 1 in 2

Prostate 1 in 6

Lung and bronchus 1 in 13

Colon and rectum 1 in 17

Urinary bladder‡ 1 in 28

Non-Hodgkin lymphoma 1 in 46

Melanoma 1 in 52

Kidney 1 in 64

Leukemia 1 in 67

Oral Cavity 1 in 73

Stomach 1 in 82

‡ Includes invasive and in situ cancer cases

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Lifetime Probability of Developing Cancer, by Site, Women, US, 2000-2002*

Site Risk

All sites† 1 in 3

Breast 1 in 8

Lung & bronchus 1 in 17

Colon & rectum 1 in 18

Uterine corpus 1 in 38

Non-Hodgkin lymphoma 1 in 55

Ovary 1 in 68

Melanoma 1 in 77

Pancreas 1 in 79

Urinary bladder‡ 1 in 88

Uterine cervix 1 in 135

Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0 Statistical Research and Applications Branch, NCI, 2005. http://srab.cancer.gov/devcan

* For those free of cancer at beginning of age interval. Based on cancer cases diagnosed during 2000 to 2002.

‡ Includes invasive and in situ cancer cases

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X-Ray Diagnostic Imaging

Includes planar x-ray (no depth resolution), CT, PET, other NM imaging modalities

Used in screening, diagnostic work-up, image-guided biopsy and therapeutic delivery

X-ray and CT: broadband, 20 – 200 keV, typically 80 – 120 keV Bone: photoionization; soft tissues: Compton scattering Relies on tissue density changes to detect soft tissue

abnormality

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Energy range selection: Compromise between Image

Contrast and Patient Dose (absorption)

Lower energy: greater contrast in transmission radiograph between different tissue compositions but needs higher exposure due to higher linear absorption

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Resonant Spectroscopic Imaging: a paradigm change?

Need: Narrowband (tunable?) light source Elemental composition differential between

malignant and normal tissues Or tumor-seeking nanoparticles tagged with known metals

(nanogold…) as exogenous contrast agents

Significant difference between resonant absorption peaks and background cross sections (10^4?)

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Radiation Therapy

Mostly delivered by linear accelerators at 6 – 25 MV (broadband, spectral peak ~ 1/3 of max. accelerator energy)

Sometimes delivered inside the tumor (“brachytherapy”) by various implantable radioisotopes, 20 – 600 keV

Primarily Compton scattering Relies on geometric arrangement of multiple beams/sources to

achieve optimized dose delivery to tumor and sparing of normal or critical tissue Expensive alternative: proton (or carbon ion) therapy, Bragg peak

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10

11

150 Gy

Day 34

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Resonant Activation Therapy: a paradigm change?

Possible scenarios: Deliver energy-optimized radiation directly to

preferentially dose tumor tissue based on elemental composition differences

Two step process: high-energy radiation is directed to a site doped with heavy elements (nanoparticles), which would be thereby pumped to undergo fluorescent emission

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Geraki 2004, City University, London

X-ray fluorescence and energy dispersive x-ray diffraction for the quantification of elemental concentrations in breast tissue

Synchrotron-based system used for detection of x-ray fluorescence emitted from iron, copper, zinc and potassium in healthy and cancerous breast tissues.

All 4 elements are found in elevated levels in tumor (less pronounced for iron, copper and more for potassium and zinc)

Kidane 1999, UCL

X-ray scatter signatures for normal and neoplastic breast tissues

100 excised tissue samples measured by energy dispersive x-ray diffraction system over the momentum transfer range of 0.70 to 3.50 nm(-1)

Shape of the scatter spectrum and relative intensity diagnostic. The shapes are significantly different between tissue types in the range 1.0 to 1.8 nm(-1)

Fernandez 2002, U. Helsinki

Small-angle x-ray scattering studies of human breast tissue samples

Small-angle x-ray scattering patterns recorded from breast tissue samples containing healthy and cancerous regions, and compared with histo-pathological observations

Average intensity of scattering from cancerous regions is an order of magnitude higher than the intensity from healthy regions. Differences of the SAXS patterns are large and distinctive enough to suggest diagnostic power.

Arfelli 2000, U. Trieste

Mammography with synchrotron radiation: phase-detection techniques

Evaluated the effect of the use of synchrotron radiation to detect phase perturbation effects, which are higher than absorption effects for soft tissue in the energy range of 15-25 keV

Image quality of synchrotron radiation images was considerably higher, and the delivered dose was fully compatible with conventional techniques.

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Marziani 2002, U. Ferrara & INFN

Dual-energy tissue cancellation in mammography with quasi monochromatic x-rays

Several images acquired in the energy range 17-36 keV using a quasi-monochromatic x-ray source and a scintillator-coated CCD detector. Images acquired at high and low energies were nonlinearly combined to generate two energy-independent basis images. Suitable linear combinations of these two basis images result in the elimination of the contrast of a given material with respect to another. This makes it possible to selectively cancel certain details in the processed image.

Carroll 1991, Vanderbilt U.

Generation of "soft x-rays" by using the free electron laser as a proposed means of diagnosing and treating breast cancer

The absence of Compton scatter and the photoelectric interaction within tissues improves conspicuity of lesions by 2 – 6 times. Increased attenuation of x-rays in malignant vs. normal tissues makes tumors more obvious. K-edge subtraction allows chemical analysis of tumors in vivo. Radiation dose 1/10 – 1/50 that delivered by conventional technique. This allows for an increased sensitivity and specificity and permits prediction of histology, negating necessity for biopsies.

Carroll 1994

Attenuation of monochromatic X-rays by normal and abnormal breast tissues

X-ray linear attenuation coefficients were measured in the energy range 14.15 to 18 keV, using monoenergetic x-rays from beamline X-19A at the National Synchrotron Light Source at Brookhaven National Laboratory

The mean of linear attenuation coefficients for cancers was 10.9% higher than the mean of normal tissues. CONCLUSIONS. Differences in the linear attenuation coefficients of monochromatic x-rays between 14.15 and 18 keV do exist between normal and cancerous tissues, but there is some degree of overlap.

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Summary

Conventional diagnostic and therapeutic x-ray sources are not energy-optimized for selective targeting of cancer tissue

Preliminary investigations suggest existence of a diagnostic/therapeutic advantage at selected energies

Resonant Spectroscopy Oncology may open up a new field of biomedical research