Use of RIB facilities for producing Use of RIB facilities for producing isotopes for cancer treatment by isotopes for cancer treatment by

DARTDART

Itzhak Kelson

Tel Aviv University & Althera Medical Ltd

DART in a nutshellDART in a nutshell

• DART (Diffusing Alpha-emitters Radiation Therapy): a new concept in radiation therapy which may enable therapeutic tumor doses with negligible damage to nearby healthy tissue

• Comprises three elements:

1. The use of alpha particles rather than photons or electrons

2. Enhancement of the therapeutic range of alpha particles from microns to millimeters

3. Utilization of the different properties of malignant and healthy tissues to ensure minimal collateral damage

Alpha particle essentialsAlpha particle essentials

• Emitted by readily available isotopes

• Densely ionizing (LET ≈ 100 keV/ µm)

• Range in tissue: 40 – 90 µm

• Possess all benefits of high-LET radiation:

– Direct ionization of the DNA complex DNA lesions

– Biological effect insensitive to hypoxia, dose rate, cell cycle

• Single hit to the nucleus may induce cell death

• Short range may guarantee sparing adjacent tissue

… but also limits the use against solid tumors

The ideaThe idea

• Rather than a source that emits alpha particles - a source that emits alpha-emitting atoms

• The source is impregnated with small activities of 224Ra

• When 224Ra decays its daughter atoms recoil out of the source (Emax~100 keV)

• The atoms disperse near the source, forming a cluster of alpha emissions extending over several millimeters

Diffusing AtomsImplanted Source

Generator

228Th

α1.91 y

224Raα

3.66 d220Rn

α

55.6 s216Po

α

0.15 s212Pb

β10.64 h

212Bi

208Pb

60.6 m

stable

β

212Poα

0.3 µs

α208Tl

60.6 m

β3.05 m

224224Ra decay chainRa decay chain

228Th panel

+ V

- V

Needle (source)

Field lines

Source preparationSource preparationelectrostatic collection of electrostatic collection of 224224RaRa

A B C

D E F

All: 212Pb autoradiography of murine squamous cell carcinoma (SQ2)

Mouse treated with a placebo source

Mouse treated with a 800 nCi source

Source preparation (future plant)Source preparation (future plant)

228Th+V

-V

Typical dimensions: L=100 cm, R=3 cm

Typical 228Th activity: 10 μCi/cm2

Each unit produces ~2000 treatments/year

Design criteria for Design criteria for 228228Th Th generatorsgenerators

• 228Th activity ~10 μCi/cm2

• 224Ra desorption probability ~40%• No knock-out of 228Th atoms• Safe, low-cost production• Long operational lifetime

228228Th Production SchemesTh Production Schemes

(n,γ)σ=13b

α

β(n,γ)σ=902b

β

β β β

232U69 y

228Th1.9 y

226Ra1600 y

227Ra42 m

227Ac22 y

228Ac6.2 h

228Fr38 s

228Ra5.8 y

228Ac6.2 h

228Th1.9 y

228Th1.9 y

228228Fr scheme - quantitative Fr scheme - quantitative aspectsaspects

• Typical DART treatment ~100 μCi 224Ra (1.7×1012 atoms) 228Th atoms per treatment ~1013

• Assuming 228Fr production rate of 1012 atoms/s:

~10 seconds per treatment

~200 seconds per cm2 of generator

Design criteria for Design criteria for 228228Th Th generators - RIBgenerators - RIB

• 228Th activity ~10 μCi/cm2

• 224Ra desorption probability ~40%• No knock-out of 228Th atoms• Safe, low-cost production• Long operational lifetime