AD-4 Status Report 2010. 32 Scientists from 10 Institutions. University of Aarhus University Hospital of Aarhus University of New Mexico, Albuquerque University of Athens Queen’s University Belfast CERN , Geneva Hôpital Universitaire de Geneve
32 Scientists from 10 Institutions
University of Aarhus
University Hospital of Aarhus
University of New Mexico, Albuquerque
University of Athens
Queen’s University Belfast
HôpitalUniversitaire de Geneve
German Cancer Research Center, Heidelberg
Max Planck Institute for Nuclear Physics, Heidelberg
University of Montenegro, Podgorica
Biological Effects of Antiprotons
Are Antiprotons a Candidate for Cancer Therapy?
Dose (and tumor control) are limited due to tolerance of organs at risk
Dose to Target
Better conformity of dose to target enables application of higher doses & higher tumor control without increasing normal tissue complication rate
Particles deposit LESS physical dose in front of the tumor
and NO dose beyond the distal edge of the Bragg peak!
Detailed dose plans (including RBE) will need to be developed to assess applicability of particle types for different tumor types and locations!
BEDR = F • RBEpeak/RBEplateau
(F = ratio of physical dose in peak and plateau region)
Plot “peak” or “plateau” survival vs. absolute dose and compare to 60Co irradiation
comparing dose values needed for
for peak, plateau, and 60Co irradiation:
Relative Biological effectiveness RBE
Example: Protons at Triumf
note: clinical beams with precise dosimetry and fast dose delivery ……..Energy to achieve same clinical relevant depth and form SOBP as at CERN….
Extract survival vs. dose plot for each depth slice and calculate RBESF=10%
RBEplateau = 1.2 RBEpeak = 2.0 RBE distal = 1.5
note: good control over dose planning for SOBP……..RBEplateau= 1.2 RBEpeak= 1.73 – 2.2
note: attempt to collect data in tail for RBE analysis…….. difficult task – long irradiation times – very little effect
Additional data set in Plateau and Peak (preliminary analysis)
……detailed dose calculations and error analysis still ongoing
Mimotera, Massimo Caccia (Universita’ dell’Insumbria Como, Italy)
Long term goal: Measure LET distributions in 2D/3D
Integral, Width in X and Yfor each shot at a glance
Mimotera allows immediate response to Accelerator Problems
Failure of quadrupole was detected and repaired within 1 hour, and
12 hour irradiation of cell samples (half way completed) was saved!
Beam Eye View
Achievable Precision: +/- 1mm
289.5° Bragg Peak
293.0° distal fall-off
Distal Edge of Depth Dose Profile is detected
Resolution is limited due to distance from target and pion scattering
Monte Carlo for Clinical Example: Distance beam to detector = 30 cm
1 x 109 antiprotons (blue: 1x108)
Detection of distal edge possible with precision of 1 – 2 millimeter
g-H2AX: Phosphorylation of H2AX in the presence of Double Strand Breaks
Micronuclei: Fluorescent detection of micronuclei (parts of whole chromosomes) formed due to DNA damage, which are indicating potential of tumorigenesis
g-H2AX and Micronucleus assays are typically used to study immediate and long term DNA damage respectively
Results g-H2AX Assay
γ-H2AX foci in cells irradiated with up 1.1x109antiprotons in theplateau (blue) or SOBP (red).
SOBP antiprotons generate largerDNA double strand breaks than either plateau antiprotons or X-rays.
60 minutes after radiation no differenceis detected anymore
Mean number of micronuclei for two replicate experiments for antiproton plateau and SOBP data sets. Sub lethal damage seems to be LET dependent.
2 weeks of 126 MeV (500 MeV/c) antiprotons