Dose and microdosimetry in sub-cellular volumes associated with the uptake of

high-Z materials

Richard P. Hugtenburg1,2

1. School of Physics and Astronomy, University of Birmingham, U.K2. Queen Elizabeth Medical Centre, University Hospital Birmingham, U.K.

Synchrotron binary therapy at ESRF with cisplatin (Pt) better than BNCT for F98 Glioma cells in Fischer rats

Biston et al., 2004, Cancer Research 64 2317–2323

Cisplatin + radiotherapy

Controls

Biston et al., 2004, show that irradiation with monoenergetic synchrotron X-rays less than 500 eV above and below K-edge

of Pt are indistinguishable

Dosimeter intercomparisons on Station 16.5 – SRS

Measurement of variation of dose-rate on Wiggler 16 at the SRS (Daresbury, UK)

2.0E-05

2.2E-05

2.4E-05

2.6E-05

2.8E-05

3.0E-05

24.0 24.5 25.0 25.5 26.0 26.5 27.0

Energy (keV)

Res

pons

eG

y/m

A/S

ec0.0E+00

5.0E-05

1.0E-04

1.5E-04

2.0E-04

2.5E-04

3.0E-04

5 10 15 20 25Energy (keV)

Rela

tive

Resp

onse

Gy/

mA

/Sec

Models of the response agree with expt to within 5% over a wide range of energies (5 keV – 5 MeV)

0.0

0.2

0.4

0.6

0.8

1.0

0 5 10 15 20 25Energy (keV)

Rat

io o

f Dos

e D

iam

ond:

Ion

cham

ber

0.0

0.2

0.4

0.6

0.8

1.0

5 55 105 155 205

Enrgy (kev )

Rat

io o

f Dos

e di

amon

d/ch

ambe

r

ratio C/Wratio diam/WExp. ratioYin No. !7

Experimental set-up and Monte Carlo models

DETECTOR(DIAMOND)

PHANTOM(rw-1)

2 cmPOLYTHENE

0.03 cmDIAMOND

0.15 cmPOLYTHENE

DIAMONDDETECTOR

DETECTOR(WATER)

PHANTOM(WATER)

IONISATIONCHAMBER

1×10 mm

Synchrotron beam

Parallel Plate Chamber

1×10 mm

Synchrotron beam

Diamond Detector Impeded in RW-1

1×10 mm

Synchrotron beam

Diamond Detector Impeded in RW-1

Silver FLUORESCENT

0

20

40

60

80

100

120

140

160

-400 -200 0 200 400 600 800 1000

Gold FLUORESCENT

0

20

40

60

80

100

120

-400 -200 0 200 400 600

More detailed Monte Carlo models incorporating data obtained from µXRF

EGS4/LSCAT v. absorption models for Ag

Hainfeld et al., 2004Au nanoparticles for enhanced 250 kVp RT,PMB, 49: N309, 2004

Adam et al, 2003, Synchrotron RT of I and Gd loaded glioma, IntJ RadiatOncBiolPhys 57: 1413

Dose enhancement through high-Z targeted RT

Maximum enhancement occurs beyond K-edge

Energy used by Adam et al.

Biston et al., 2004, Irradiation above or below K-edge radiobiologically indistinguishable, Cancer Res., 64: 2317

EGS4/LSCAT versus absorption models for Pt

Dose enhancement for localised 10 mg/ml concentrations of Pt relative to that of a water-filled volume

Region size @ 10 mg/ml 78.0 keV 78.8 keV 90 keV

0.2 micron 1.02 1.20 1.16

2 micron 1.10 1.33 1.38

20 micron 1.26 1.53 1.51

Determination of energy deposition within small volumes – Going beyond dose and LET

• Tissue equivalent proportional counter (TEPC)• Lineal energy calculations via PENELOPE

Schematic and photograph of a single wire TEPC microdosimeter

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.10 1.00 10.00 100.00 1000.00

Lineal energy (keV/µm)

y.d(y

) (a

rb.u

nits)

Photons

ProtonsHeavy ions

f

Microdosimetry measurements of mixed photon neutron field using TEPC

Variation in mean lineal energy with photons energy

f

0

2

4

6

8

10

12

1 10 100 1000

Photon energy (keV)

Mea

n lin

eal e

nerg

y

y_D 1000nmy_T 1000nmy_D 200nmy_T 200 nm

Transformation rate of CGL-1 for a 29 kVp Mo X-ray mammography set relative to Sr-90 beta electrons and A-bomb like linear accelerator irradiations

Heyes and Mill, 2004, Radiat. Res. 162: 120-7

29 kVp Mo X-rays

Sr 90

A-bomb

Lineal energy spectra for 29 kVp Mo X-rays relative to Sr-90 beta-electrons

-0.10

0.00

0.10

0.20

0.30

0.40

0.50

0.01 0.1 1 10 100

y, lineal energy (keV / µm)

y. d

(y),

dose

wie

ghte

d fr

eq.

29 kVp Mo X-raysSr-90 beta-rays

Lineal energy spectra for 15 keV photons in a 2 micron site

f

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

1.80

0.1 1.0 10.0 100.0y, lineal energy (keV / µm)

y. d

(y),

dose

wie

ghte

d fr

eq.

15 keV, water15 keV, TEP15 keV TEPC meas.

Lineal energy spectra for 33 keV for a 2 micron cell

f

0.00

0.20

0.40

0.60

0.80

1.00

1.20

0.1 1.0 10.0 100.0y, lineal energy (keV / µm)

y. d

(y),

dose

wie

ghte

d fr

eq.

33 keV, water33 keV, plastic33 keV TEPC meas.

Lineal energy in water and aq. Gd inside a 1 micron cell

Lineal energy spectra from Gd particle outside a 1 micron site

f

f

Lineal energy spectra for Pt enhanced medical radiation (1 micron site)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.1 1.0 10.0 100.0

y, lineal energy (keV / µm)

y. d

(y),

dose

wie

ghte

d fr

eq.

78.0 keV in aq Pt78.8 keV in aq. Pt78.8 keV in water90 keV in aq. Pt

Lineal energy spectra from U particle enhancing natural background radiation (1 micron site)

f

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.01 0.1 1 10 100y, lineal energy (keV / µm)

y. d

(y),

dose

wie

ghte

d fr

eq.

NBG in H2ONBG near U

Acknowledgements and Participants:

University of Birmingham:Fathy Saeedi, Adam Baker, Mohammed Ariff

Queen Elizabeth Medical Centre:Stuart Green, Alun Beddoe, Bleddyn Jones

University of South Australia:John Pattison

University of Setif, Algeria:Zine-El-Abidine Chaoui