18th ICIS, Lanzhou, 2019

Present status of ion sources

at QST-NIRS

and carbon-ion radiotherapy facilities

Masayuki Muramatsu1), Atsushi Kitagawa1), Ken Katagiri1),

Satoru Hojo1, Takashi Wakui1), Noriyoshi Suya1), Mitsuru Suda1),

Takahiro Ishikawa1), Masakazu Oikawa1), Tsuyoshi Hamano1) ,

Katsuyuki Takahashi2), Taku Suzuki2) Fumihisa Ouchi2), Hiroshi Ii2),

Tadahiro Shiraishi2), and Toshinobu Sasano2)

1)National Institute of Radiological Sciences,

National Institutes for Quantum and Radiological Science and Technology (QST-NIRS),

4-9-1 Anagawa, Inage, Chiba 263-8555, Japan2)Accelerator Engineering Corporation,

3-8-5 Konakadai, Inage, Chiba 263-0043, Japan

QST

National Institutes for Quantum and Radiological Science and Technology

National Institute of Radiological Sciences

Rokkasho Fusion Institute

Naka Fusion Institute

Takasaki Advanced Radiation Research Institute

Kansai Photon Science Institute

Injector + LEBTCEA Saclay

RFQINFN Legnaro

QSTMEBT

CIEMAT Madrid

SRF LinacCEA Saclay

CIEMAT MadridHEBT

CIEMAT Madrid BDCIEMAT Madrid

DiagnosticsCEA Saclay

CIEMAT Madrid

RF PowerCIEMAT Madrid

CEA SaclaySCK Mol

CryoplantCEA Saclay

BuildingAuxiliary SystemControl system

InstallationQST

was established in April 2016(http://www.qst.go.jp)

QST-NIRS

Ion Beam Technology at QST-NIRS

QST-NIRS is a lifescience institute, including:

- the effects of radiation on the human body; protection from radiation,

- diagnosis and treatment of radiation injuries

- medical applications of radiation.

QST-NIRS maintains accelerators, including:

- two tandem accelerators,

- three cyclotrons,

- one heavy-ion accelerator complex consisting of two synchrotrons and

four linacs for heavy-ion radiotherapy.

Ion Beam Technology at QST-NIRS

HIMAC

Contents

1.Operation summary

2.Ion sources for carbon-ion radiotherapy

3.New developments

Contents

1.Operation summary

2.Ion sources for carbon-ion radiotherapy

3.New developments

Neutron exposure

DOSE RATE

Distance Diameter Dose

Sample – of field rate

Target

(mm) (mmf) (Gy/h)

710 120 7.62

1170 240 2.18

1740 ~300 0.22

TARGET8Be(D, n)9B

reaction

Thickness = 3mm

Multi-cusp ion source

Output current = 600 mA

On target (3~4MeV) = 500 mA

Trends•Animal experiments decreased.•Device developments for BNCT increased.

HVEE

2MV Tandetron

(hours)Lifescience Physics /

Devicedevelopment

Maintenance/ Beam

development2010 472 99 10082018 168 872 168

Irradiation to animals

PIXE & micro beam irradiation

Droplet-PIXE

conventional PIXE analysis

Single particle irradiation system to cell

(SPICE)

Duoplasmatron

1H+ 25(mA)

4He2+ 1 (mA)

Characteristics;

1. 3.4 MeV proton microbeam

2. Focusing microbeam system using

triplet quadrupole magnet

3. Upward vertical beam line

4. Beam size: 2 mm in diameter (GOAL)

5. Maximum speed for irradiation:

400 – 500 cells per minute

HVEE 2MV Tandetron

Lifescience / Environmental

Physics / Device development

Maintenance / Beam development

Lifescience

Device development

Maintenance / Beam development

2010 2018

SPICE SPICE

PIXEPIXE

Trends• Interests in the

micro beam continuously increased.

Small cyclotrons for RI production

SHI HM-18 cyclotron

JSW BC-2010 cyclotron

Internal neagtive PIG

H- 20 (mA)

D- 10 (mA)

2010

Trends

• The majority in 2010

was the verification

of carbon-ion

therapy.

• The majority in 2018

is the probes in a

brain.

• Many major

compounds in 2010

have not been

utilized anymore ▲.

GBｑ times person GBｑ times GBｑ timesPBB3 37 39 39 3 13 － －BTA 135 70 117 0 1 － －MTP38 0 0 0 12 30 － －RAC 0 0 0 2 5 － －FLB 28 15 15 0 0C22b 0 0 0 17 34 － －GW2580 0 0 0 7 18 － －ABP688 32 19 19 5 9 － －MNAH 0 0 0 1 15 － －AZD1283 0 0 0 2 5 － －MP4A 0 0 0 3 13 － －AC5216 0 0 0 11 27 － －MAGL-1 0 0 0 17 45PP-Amide-3 0 0 0 3 9MET 0 0 0 0 0 － －SCH 55 31 31 1 2MeLeu 0 0 0 0 0 － －MePro 0 0 0 0 0CH3I 0 0 0 2 50 － －Others 0 0 0 60 218 － －

15O H2O 0 0 0 94 17 － －

PMPBB3 98 56 110 31 71 － －R-PMPBB3S-PMPBB3FEAKT 0 0 0 5 16 － －MNI-659 35 46 46 3 8T-401 13 11 11 6 15FEtDAA 1 1 1 0 1 － －FEDAC 0 0 0 3 7 － －FETMP 0 0 0 5 19 － －FMeNER 0 17 17 0 0 － －FDG 72 16 36 0 0 － －F- 0 0 0 1 14 － －Others 0 0 0 13 49 － －

28Mg Solution 0 0 0 0 0 0.0 6

64Cu Solution 0 0 0 55 50 13 11

67Cu Solution 0 0 0 0 1 － －

68Ge Solution 0 0 0 0 0 － －

74As Solution 0 0 0 0 2 － －

89Zr Solution 1 5 0.1 3

111Ag Solution 0 1 － －

124I Solution 0 0 － －

191Pt Solution

211At Solution 0 0 0 2 19 1 4

Total 321 442 789 24

Human Animal Deliver to hospital

18F

11C

Nucleid Compound

RI production

52%

Physics

14%

Development of

detector

1%

Biology

6%

Service for a

charge10%

Development of

accelerator

17%

Others

0%

Radiation safety

monitoring

0%

RI production

28%

Physics

13%

Development of

detector

4%

Biology

1%Service for a

charge

12%

Development of

accelerator

34%

Others

8%

Radiation safety

monitoring

0%

NIRS-930 Cyclotron

External Kei source

H+ H2+ D+ 12C4+ 13C5+ O5+ Ne6+

200 200 200 70 25 10 2 emA

2010

2018

Thomson / SHI K=110 cyclotron

RI production

Trends in nuclear pharmaceuticals

For diagnosis and research:

- The majority in 2018 was 11C-BTA.

- Molecular imaging probes for changing in the protein tau in the

brain like 18F-PMPBB3, 18F-MNI-659 interested.

For Targeted Radioisotope Therapy:

- Several a and b emitters interest for treatment

(Therapeutics + Diagnosis = Theranostics)

- 211At antibodies have been developed and are tested by animal

experiments.

- 225Ac has been produced and its 3-D imaging were also obtained.

- 64Cu-ATSM therapeutic agent has been developed by QST-NIRS,

and its clinical trial has started in 2018.

Block diagram of HIMAC beam courses

: Treatment room

: Experiment room

: Ion source

: Synchrotron

: Linac

PH1 PH2

SB1

SB2

B

BIOC

C

A

E

F

G

MEXP

Kei2

NIRS-

HEC

NIRS-PIG

NIRS-ECR

Time sharing acceleration

and timings of injection

into the synchrotrons

Kei2 ECRIS 10GHz NIRS-ECR IS 18GHz NIRS-HEC ECRISNIRS-PIG IS

From H to Xe

Max. energy 800 MeV/u

Statistics of biology experiments

*The above were the scheduled time. The failure rate is 0.2%~0.3% every year.

Trends

• Required ion

species are not

so changed

from 2014.

• Necessary

beam time

increased.

• Main topics are

charged particle

therapy and the

risk in the

space

environment.

Beam time of biology experiments 1st half 2nd half 1st half 2nd half Total

Number of users 60 61 46 59 105

Number of Experimets 150 249 163 252 415

Total beam time (hours) 337 568.5 560 912.5 1472.5

Mean time for one experiment (hours) 2.25 2.28 3.44 3.62 3.55

Total time of each ion species (hours)Max.

energy(MeV/u)

Max.intensity

(pps) Ratio(%)

H 430 1.8 x 109 0.0 0.0 33.0 55.5 6.0

He 430 1.8 x 109 30.0 16.0 43.5 92.0 9.2

C 430 1.8 x 109 232.5 404.0 343.0 492.0 56.7

O 530 1.8 x 109 2.5 0.0 7.5 29.0 2.5

Ne 600 1.8 x 109 5.5 17.0 24.5 58.5 5.6

Si 600 4.8 x 109 13.5 32.5 14.0 31.0 3.1

Ar 560 4.8 x 109 5.5 12.0 4.0 12.5 1.1

Fe 500 4.8 x 109 47.5 87.0 72.5 126.5 13.5

Kr 560 4.8 x 109 0.0 0.0 0.0 0.0 0.0

Xe 500 4.8 x 109 0.0 0.0 18.0 15.5 2.3

2014 2018

Contents

1.Operation summary

2.Ion sources for carbon-ion radiotherapy

3.New developments

ECRISs for carbon-ion radiotherapy

Topics at Poster WedP44 presentation

Bone & soft tissue, head & neck, and

prostate tumor have been covered by the

Japanese national health insurance.

At present, thirteen facilities are under

operation and six are under commissioning

or construction worldwide.

All facilities mainly use carbon

ions for the treatment. ECRISs

are utilized for the production of

carbon ions and completely

satisfy medical requirement.

ECRISs at facilities

Kei2Mirror magnetic field

material Permanet (NdFeB)Injection field 0.87 T (fixed)

Minimum B field 0.25 T (fixed)Extraction field 0.59 T (fixed)

Axial magnetic fieldmaterial Permanent (NdFeB)

Surface field 0.75Effective chamber size

Length 105Diameter 55

MicrowaveFrequency 8 - 11 GHz

Power 300 WExtraction

Voltage 30 kV

KeiGM1 KeiSA

Saga-HIMATGHMC

Kei2

M. Muramatsu et al., Rev. Sci. Instrum. 76, 113304 (2005).

*since

Oct. 2018

Location of

hospital

Frequency of

ion source

maintenance

2017-2018

Serious

failure

in 2017-

2018

Gunma 2 per year 0Saga 1 per 2year 0Kanagawa 1 per 2year 0Osaka* 1 per half year -Yamagata commissioning -Taipei manufacturing -Seoul manufacturing -

GHMC

Contents

1.Operation summary

2.Ion sources for carbon-ion radiotherapy

3.New developments

He C Ne<Physical>

Longitudinal - Bragg peak

Distribution

- Projectile fragmentation

Lateral - Multiple scattering

Distribution

<Biological>

- Relative Biological Effectiveness

- Oxygen Enhancement Ratio

- Cold spot problem

Multiple ion-species irradiation

Biological optimization of irradiation

C io

ns fo

r alm

ost re

gio

ns

Heavier ions for central

radioresistance regions

Lighter ions near

critical organs

Critical

organs

T. Inaniwa et al., Phys. Med. Biol. 62, 5180 (2017).

Mizushima et al. WedP17

Development of multiple ion source

Plasma chamber

500l/sTMP

500l/sTMP

Extraction electrode

(movable)

Einzel lens

Acceleration gap

(Insulator)

Analyzer magnet

Gas inlet

Waveguide

High voltage

platform

Sextupole magnet

Mirror magnet

Faraday Cup & Slit

Plasma chamber

500l/sTMP

500l/sTMP

Extraction electrode

(movable)

Einzel lens

Acceleration gap

(Insulator)

Analyzer magnet

Gas inlet

Waveguide

High voltage

platform

Sextupole magnet

Mirror magnet

Faraday Cup & Slit

18GHz NIRS-HEC

18GHz NIRS-HEC 10GHz Kei series

He2+ 940 1185 1920

C4+ 290 870 565

O5+ 330 900 187.5

Ne7+ 245 391 50.5

Ion species Intensity (e microA)

Improvementsare necessary

New designObtained by existed sourcesRequired for thefuture facility

Method of development: 1. Search optimized parameters with NIRS-HEC under the poor conditions;

i.e. lower frequency, magnetic field or microwave power2. Try to realize above conditions by a permanent magnet ECRIS.

Decrease frequency

18 -> 14 GHz

500 e microA for C4+ has been obtained.(ECRIS2016)

Decrease magnetic field

1.29 -> 1.14 T

This is able to be

realized by permanent

magnets.(ICIS2017)

Recent progress

Parameter search with NIRS-HEC Mechanical design and cooling consideration

Improve the switching time between ion species

Required beam

current: 940eμA

Required beam

current: 245eμA

Upstream：840A

Required beam

current: 940eμA

Required beam

current: 245eμA

Upstream：840A

Gas mixing for C4+ production

C4H10+He

Application of radioactive nuclear beam

Ion sources for radioactive beams

e~10%e~60-

80%

N~101

3

K. Katagiri et al., Rev. Sci. Instrum. 89, 113302 (2018).

12C

12C11C

11C, 10C ...

15O

13N 11C

a pair of

annihilation g-ray

positron

b+ emitting

nuclei

decay

3. Radioactive beam

directly shows it’s position

with high signal-to-noise ratio.

1. In-vivo activation:

Stable beam produces

b+-emitter as target

fragment.

2. Autoactivation:

Stable beam changes to

b+-emitter as projectile

fragment.

ESIS for charge breader is being studied in

collaboration with JINR

Summary

• Ion source are an essential tool for life science study.

• Trends in 2018 at QST-NIRS were

- Device developments for BNCT

- Micro beam technique for cell irradiation

- Probes for the protein tau in the brain

- 221At, 225Ac a and 64Cu b emitters for TRT

• Relativistic ion beams between H and Xe have been used by many

biology users.

• ECRISs sustain carbon-ion radiotherapy worldwide

- No serious failure in 2017-2018

• New developments of ion sources are in progress.

- Improvement of permanent magnet ECRIS for the future heavy-ion

radiotherapy

- Construction of single charged ion source for the medical

application of RI beam is in progress.