Applications of Particle Accelerators in Medical Physics.

CERN-KTT-2013-001

10/09/2008

G. Cuttone,

Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud

V. S. Sofia, 44 Catania Italy- Cuttone@lns.infn.it

1. INTRODUCTION

Particle accelerators are often associated to high energy or nuclear physics. As well

pointed out in literature [1] if we kindly analyse the number of installation worldwide we can

easily note that about 50% is mainly devoted to medical applications (radiotherapy, medical

radioisotopes production, biomedical research). Particle accelerators are also playing an

important indirect role considering the improvement of the technical features of medical

diagnostic. In fact the use of radionuclide for advanced medical imaging is strongly

increasing either in conventional radiography (CT and MRI) and also in nuclear medicine for

Spect an PET imaging. In this paper role of particle accelerators for medical applications will

be presented together with the main solutions applied.

2. THE ROLE OF PARTICLE ACCELERATORS COMBATING CANCER.

At the beginning of the third millennium one European citizen out of three will have

to deal with a cancer episode in the course of his/her life. Worldwide the estimated

number of new cancer cases each year is expected to rise from 10 millions in 2000 to 15

millions by 2020. Cancer is currently the cause of 12% of all deaths worldwide. Within

the European union it is over 1,5 million new cancer cases that are diagnosed every year

and over 920000 people die of cancer with the two leading cause of cancers in Europe are

Breast and Prostate. Therefore combating cancer is a major societal and economical

issue for Europe and to face up these new challenges strong mobilisation among the

scientific community and industrial manufacturers is needed.

Today’s approaches to treat cancer are the surgical removal of the tumour tissue,

radiotherapy, chemotherapy, and immunotherapy. Most scientists are confident that in the

long run significant improvements in cancer cure will come from immunotherapy and/or

gene therapy and drug targeting ; research towards such systemic treatments is and will

be of the utmost importance. However, in the mean time, radiotherapy either combined

with surgery or as main treatment modality still remains the most effective technique to

treat cancer.

More than a half of all cancer patients are now treated by radiation therapy thanks to

the technical progress made with irradiation equipment in the last ten years. For external

radiation therapy (RT), for instance, high energy photon or electron beams are mainly

produced by linear accelerators, while a very limited number of proton synchrotrons or

cyclotrons are used for the treatment of cancers close to vulnerable organs such as the

eyes and the optical and auditory nerves, spinal cords. For internal radiation therapy,

brachytherapy, radioactive sources are put in the tumour with undeniable advantages for

the patient in given situations.

In an abstract from Annex A of "Europe Against Cancer" [2] in 1994, the present

status of cured patients following a specific treatment shows that in Europe at present

45% of all the treated patients are "cured", which means that these patients have a

symptom-free survival period exceeding five years. About 90% of the cured patients (i.e.

40% of the total) are cured because of loco-regional control of the primary tumour, i.e.

because of surgery and radiotherapy. Of course, the treatments are almost always

accompanied by chemotherapy to prevent the spreading of metastasis. In fact surgery and

radiotherapy alone are successful in 22% and 12% of the cases respectively. When

combined, they account for another 6% of the cases so that radiotherapy is involved in

almost half of the curative treatments of loco-regional type. Despite a widespread belief,

all the other systemic treatments account for 5% only of the cured patients. There is

ample space for improvements here, because 37 % of the tumours are metastatised at the

moment of diagnosis and cannot be cured with loco-regional treatments alone.

Three strategic approaches are generally proposed:

• Early detection and improved diagnosis based on widespread screening with

the aim of reducing the number of late diagnoses.

•

Improved local treatment, avoiding poor treatments, to treat tumours with

difficult localisations and tumours which are radio-resistant to conventional

radiotherapy.

• Improved systemic treatments combined with local treatments which are able

to reduce the tumour mass significantly.

Improving loco-regional treatments is essential for at least two reasons. First, 18% of

all the patients die because of a primary tumour without metastases. This implies that the

percentage of the cured patients could pass from 45% to about 65 %, if all primary

tumours could be locally controlled. Secondly, in the long term “immunochemotherapy

might be extremely useful in cancer treatment; it will, however, only be effective against

a relatively small number of cells and such treatments will thus need to be used in

conjunction with other anti-cancer modalities such as surgery, radiotherapy and

chemotherapy".

For all these reasons it is generally approved that to increase the dose at the target or to

get a better dose conformation to spare surrounding health tissue it is mandatory to

implement new techniques like Conformal Radiotherapy, Intensity Modulation

Radiotherapy (IMRT) or hadrontherapy (HT). These techniques together with stereotactic

treatment (ST) or brachytherapy (BT) represent nowadays the new frontier of the

radiotherapy daily implemented in the clinical reality of European Union (EU) countries.

The development of three-dimensional (3D) conformal radiotherapy, in which the

high-dose volume matches the target volume and avoids radiosensitive normal tissues,

has been a major theme for improving the physical basis of radiotherapy [3]. Intensity-

modulated radiation therapy (IMRT) is the most advanced form of conformal

radiotherapy. It is anticipated [4] that in the next ten years it will be routinely possible to

automatically shape radiation fields, modulate the intensity such modulation under

computer control, verify that radiotherapy is accurately delivered, predict the clinical

outcome via biological models, and if not eliminate uncertainties, quantify them. It may

become possible to customize radiotherapy to radio sensitivities of individual patients.

Conformal radiotherapy may be broadly divided into two classes of techniques, i.e.

those which employ field-shaping alone and those which also modulate the intensity of

fluence across the geometrically-shaped field. The basic idea behind IMRT is that by

sparing more volume of the organs at risk the dose to the planning treatment volume can

be escalated and thus result in improved tumour control probability. The types of

radiation used in IMRT may be photons, protons and light ions.

Protontherapy (PT) and heavier charged beam therapy (IT) shares with photon IMRT

the characteristics of an enhanced precision in the dose delivery to the target. For these

reason protontherapy scores, as photon IMRT, better clinical results than conventional

radiotherapy but also faces the same challenges of achieving a higher precision in target

localisation. Moreover also from the radiobiological point of view protons and especially

heavy ions have demonstrated major effects giving possibility to change the fractioning

scheme (ipofractioning) and the total dose.

An other challenge concerns brachytherapy where high quality treatment requires

development of new radiation delivery systems and sensors for checking the main

biological and dosimetric parameters of the patient. Short life radioactive substances are

incorporated in the cancerous tumour allowing the patient to spend a quasi normal life

with minor limitations. Brachytherapy, also known as Curie therapy is undergoing rapid

changes in technology. In Europe, high dose rate (HDR) brachytherapy using after-

loaders with Iridium sources is the most common technology. But, specially for the

treatment of prostate cancer, low dose rate (LDR) brachytherapy using sealed seeds filled

with local action radioisotope such as Iodine 125 or Palladium 103 are increasingly used.

Innovative research have to be carried out in order to ensure a better quality and

efficiency of treatments. This advanced brachytherapy (BT) treatment needs validation

and new requirements for patient safety. On the other hand accelerator based facilty have

to be developed in order to get reliable production of those radionuclides.

Although IMRT, external beam radiotherapy (photons, protons, hadrons) and

advanced brachytherapy (BT) promise great benefits for optimised cancer treatment, a

considerable number of technical restrictions and basic questions have to be resolved to

realise the expected benefits.

In radiation oncology (IMRT, PT and BT), the main difficulty is to deliver both a

precise and accurate large dose of radiation to destroy cancer cells in a diseased organ

and a dose as low as possible to sound organs. Delivered doses to tumours being highly

above the lethal level for a total body irradiation, thus doses have to be delivered with

extreme precaution. In coming years, it will be necessary to find treatment protocols

based on IMRT and advanced BT techniques. It is therefore crucial to be able to more

accurately locate the tumour in treatment, to accurately determine the dose required and

to fully spare organs that are vulnerable or present a high structural heterogeneity, in

order to reduce the doses delivered to healthy organs with proper monitoring throughout

the duration of the treatment.

Functional imaging by means of positron emission tomography (PET) or single photon

emission computerized tomography (SPECT) can facilitate the evaluation of tumour

physiology, metabolism and proliferation [5]. These are parameters determining outcome

to radiotherapy treatment. PET can be used to get also quantitative information about the

the in vivo distribution of positron-emitting radioisotopes (Fluorine-18, Carbon-11,

Oxygen-15) that can be added or substituted into biological relevant compounds. SPECT

may be used to image compounds labelled with indium-111, technetium-99m, and

Iodine-123 in vivo. The application of these techniques represents a new frontier in

combating cancer permitting not only the early diagnosis of tumour but also the

biological target definition in radiotherapy like tumour metabolism, hypoxia, growth

factor receptor expression, tumour apoptosis. These parameters can be used as predictors

or early markers of response to radiotherapy, opening a new frontier of study and clinical

application.

3. ACCELERATORS FOR MEDICAL APPLICATIONS: A SHORT HISTORY

The development of particle accelerators started in the past century and was well

summarized by P.J Bryant [6]. It is mainly based on three acceleration mechanism:

DC Acceleration

Resonant Acceleration

Betatron Mechanism

Following the first mechanism a wide set of electrostatic machines (Cockroft Walton

generator, Van Der Graaf generator single or double stage) have been developed. Their

use for medical applications has been very limited.

Resonant acceleration proposed by Ising in 1924 is based on the use of alternating

electric fields. He suggested to accelerate particles with a linear series of conducting drift

tubes and in 1928 Wideroe demonstrates his validity building a 1 MhZ, 25 kV oscillator

able to accelerate 50 keV potassium ions. He realized the first linear accelerator (LINAC)

prototype. At that time the realization of a LINAC was really difficult so that we have to

wait until 1930 for the realization of the first real particle accelerator based on this

mechanism. In fact at that time Lawrence realized the first fixed frequency cyclotron

accelerating 1.25 MeV proton beam. Cyclotron was limited in energy by relativistic

effects so that we had to wait for increasing energy until 1944. At that time Veksler

discovered the principle of phase stability and invented the synchrotron. LINAC,

CYCLOTRON and SYNCHROTRON nowadays are particle accelerators used for

medical applications.

Betatron mechanism originally discovered by Wideroe in 1923 and never published,

found his proof in 1940 when Kerst re-invents the betatron and built the first working

machine for 2.2 MeV electrons. Betatrons were used in radiotherapy for many years.

Today they have been fully replaced by electron LINAC.

4. ACCELERATORS FOR RADIOTHERAPY

In conventional radiotherapy, electron LINAC are mainly used. A 3 GHz accelerating

structure is used. The electrons are thermo-ionically emitted from a concave metal

cathode at 1000 °C and accelerated in the gun to about ¼ the velocity of light by a pulsed

DC electric field. Then they are formed into a pencil beam by a convergent electric filed

between the gun electrodes. The RF electric field in the accelerating tube then forms the

electron into bunches and accelerates them to more than 99% of light velocity, increasing

their mass. The electrons are then used to bombard a target tipically done in tungsten.

Electrons hitting the target will produce Bremstralung Radiation in the forward direction.

X-rays so emitted are used for the therapy. Two sets of tungsten blocks allow the sizes of

the radiation beam (square or rectangular sections) to be adjusted. All modern medical

electron linacs employ an isocentric gantry. The accelerator wave guide is mounted in the

gantry, either parallel to the gantry axis if a beam bending magnet is employed or

perpendicular to the gantry axis if a beam bending magnet is not required. A simplified

block diagram of a medical linear accelerator is represented in fig. 1. The new frontier of

these machines is represented by multileaf collimator consisting of two of leaves (up to

120) which can be moved independently allowing the application of irregularly shaped

beams better adapted to the complex shape of the target volume. Moreover they permit

the application of special techniques like the intensity modulation (IMRT), dynamic

therapy and radiosurgery.

New frontier in radiotherapy is nowadays represented by the use of hadrons. In fact

heavy particles (protons, light ions, neutrons) offer a unique opportunity for improving

the quality of radiation therapy. Their use has been pioneered over four decades at

Berkley where there was a very active collaboration among nuclear physicist, accelerator

physicist, physicians and biologist. Th

is is well proven looking to the history of the

accelerators, especially of cyclotrons. E. Lawrence, the cyclotron father, started in thirties

a collaboration with physicians and biologist in the use of neutrons for cancer treatment.

The rationale base for the use of neutrons was not available at that time even if an

expected high incidence of late morbidity was shown. Only in sixties biologist showed

the role of the LET (Linear Energy Transfer) and the concept of radioresistance was

developed. In 1946 R. Wilson mentioned that the properties of mono—energetic charged

particles such as protons and Ions, i.e. the deposition of a large fraction of their kinetic

energy in a small volume at the end of their energy (BRAGG Peak and distal dose fall-

off), small lateral scattering, could lead to a new radiotherapic tool. The therapy with

heavy particles is based on two factors:

-Balistic effect i.e. improved physical selectivity for charged particles, which means

the delivery of a homogeneous dose to the tumour volume while minimizing the dose to

surrounding healthy tissues.

-Radiobiological effect i.e. the improved biological effectiveness (RBE) of hadrons

due to dense ionising tracks produced by these particles.

In fig.2 you can see the comparison of depth-dose distribution for various types of

radiation used in radiotherapy. It is very clear and completely accepted that the

advantages of charged particles (protons, carbon ions) with respect to photons and

electrons are well summarized in the Bragg Peak and very reduced lateral scattering

permitting the better dose conformation to the tumour sparing surrounding healthy

tissues. RBE is assumed to be unitary for photons and electrons. It is well clear as

biological effectiveness can be significantly higher for hadrons especially for carbon ions.

According to that we can state that high-LET treatment is particularly useful for

radioresistent tumours, insensitive to conventional. These statements represent the

rationale that are convincing and forcing to develop hadrontherapy facility.

These facilities are typically based on the use of Cyclotrons and Synchrotrons. In the

PTCOG website [7]is reported a short list of these facilities. According to the already

gained clinical experience main advantages can be carried for tumours close to organ at

risk, like isolated brain metastases, pituitary adenomas, arteriovenous malformations,

base of skull tumours, meningiomas, acoustic neuromas

chordomas and chondrosarcomas, uveal melanomas, macular degeneration

head and neck tumours, chest and abdomen, medically inoperable non-small-cell lung

cancer, prostate, pediatric tumours (Brain, Orbital and ocular tumors, Sarcomas of the

base of skull and spine, Acoustic neuromas).

Wide experience has been gained in the treatment of eye melanoma, considering the

reduced proton energy required, (around 62 MeV, corresponding to a beam range in

water of about 3 cm). In the following the experience gained at INFN-LNS will be

detailed reported.

Beam produced by particle accelerators are not suitable for clinical applications if a

dedicated beam delivery system is not available. Any beam delivery system must

accomplish a three-dimensional scanning of the tumour requiring lateral beam deflection,

variable range and exposure time to achieve a uniform dose. Moreover position sensitive

monitors and fast beam switch-off in case of malfunction have to be available too. The

lateral beam deflection should be obtained either by passive scattering [8] or by active

methods using magnetic field deflecting the beam realizing a beam spot scanning . The

first method is implemented in fixed beam treatment line. At PSI a discrete spot scanning

system based on the use of a kicker magnet located within a gantry has been developed

and used for clinical application. The system is shown in fig.3. In order to reduce the

dose to surrounding healthy tissues we can take advantage by using different multiple

entrance beam port coming from different directions. A device performing this task is a

rotating gantry: the beam comes in along the axis, is guided away from the centre and

bent back towards the axis orthogonally. If the beam line ends at the axis so that the

patient is located opn the axis, the gantry is called isocentric. Isocentric gantry are

significantly different when applied at cyclotrons, characterized by a fixed extracted

beam energy or at synchrotrons able to change the extracted beam energy. In fig. 3 the

PSI Gantry is showed.

5. HADRONTHERAPY FACILITIES

Different commercial solutions are now available. A 235 MeV proton beam room-

temperature cyclotron has been studied and developed by IBA in Belgium. This cyclotron

with associated gantry has been installed at Massachusetts General Hospital in Boston

(USA) going in clinical operation in 2002.

In 2001 PSI, Switzerland, announced officially to have chosen ACCEL Instruments

GmbH as the supplier of a 250 MeV superconducting cyclotron. The cyclotron will be

part of PSI´s proton therapy program PROSCAN. It includes the development of a

dedicated proton source and beamlines to supply up to 250 MeV protons to the existing

PSI Spot-Scanning-Gantry for deep-seated tumor treatment, a new industrialized Gantry

with advanced technical features and a horizontal beam for treatment of eye tumours.

ACCEL had proposed a very powerful proton accelerator based on a conceptual design

elaborated earlier by Prof. Henry Blosser and his team at the National Superconducting

Cyclotron Laboratory of Michigan State University. The 250 MeV cyclotron is designed

for highest extraction efficiency, low energy consumption, high reliability and most

modern operation features, e.g. spot scanning and beam intensity modulation. It uses

superconducting main coils allowing for moderate HV and RF power levels. The design

nevertheless provides full accessibility to the cyclotron parts relevant for operation and

maintenance. The cyclotron will be operable as a turn key system in mid 2004.

In Italy an hadrontherapy facility is foreseen, the ‘Centro Nazionale di

Adroterapia’(CNA). It is a hospital based facility dedicated to advanced tumour

treatments with hadron beams and to advanced research (clinical, radiobiological and

technical) made possible by their availability. The main requirements, considered during

the CNA design, and the solutions adopted fully satisfy the following main criteria:

safety, reliability, maintainability and availability. These criteria have driven the

technological choices in so many respects that it is not possible to enumerate all of them

in this short introduction, but they will be the core arguments of the authorisation

documents that will be presented to obtain the permissions to run the centre and to treat

patients.

The CNA design (a preliminary view is shown in Fig. 4) is based on the following

assumptions:

•

the Centre will be devoted to the treatment of deep-seated tumours (up to a depth of

27 cm of water equivalent) with light ion beams (mainly C

, but also protons and

possibly He

, Li

, Be

, B

and O

, but this last with a reduced range). All

available light ions will be delivered in each treatment room with the exception of the

room foreseen to be equipped, in a second stage, with a gantry for protons;

• the full-size CNA will have 5 treatment rooms: 3 rooms with fixed beams and 2

rooms with gantries. To reduce the initial investment it is proposed to first equip 3

treatment rooms with 4 fixed beams, three horizontal and one vertical beams (CNA -

Phase 1). At a later stage (CNA - Phase 2), two other rooms will be equipped with

gantries: one gantry for protons and one gantry for light ions.

The eye melanoma treatment with proton beam represents the more significative clinical

experience. More than 7000 patients have been successfully treated in different facilities.

More significative experience has been gained in Europe at PSI, CCO and Nice, Orsay

and Berlin while in USA MGH and Loma Linda are the main centers [9].

Also in Italy is now available a protontherapy center. In fact at the INFN Laboratori

Nazionali del Sud in Catania (Italy) the first Italian protontherapy facility, named

CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) has been realized

in collaboration with the University of Catania.

It is based on the use of the 62 MeV proton beam delivered by the K=800

Superconducting Cylotron installed and working at LNS since 1995. The facility is

mainly devoted for the treatment of ocular diseases like uveal melanoma. A beam

treatment line in air has been realized together wth a dedicated positioning patient

system. The facility is in operation since the beginning of 2002 and 40 patients have been

successfully treated up to now. The CATANA proton beam line has been entirely

realized at LNS and its global view is shown in Fig.5. The proton beam exits in air

through 50 µm Kapton window placed at about 3 meters from isocenter. Before the

window, under vacuum, is placed the first scattering foil made by a 15 µm tantalum. The

first element of the beam in air is a second tantalum foil 25 µm thick provided with a

central brass stopper of 4 mm in diameter The double foils scattering system is optimized

to obtain a good homogeneity in terms of lateral dose distribution, minimizing the energy

loose. Range shifter and range modulator are placed downstream the scattering system

and mounted on two different boxes. Two diode lasers, placed orthogonally, provide a

system for the isocenter identification and for patient centering during the treatment. The

emission light of a third laser is spread out to obtain the simulation field.

A key element of the treatment line is represented by the two transmission monitor

chambers and by the four sector chamber, implemented to have an on-line control of the

dose furnished to the patients and an information on beam symmetry respectively. The

last element before isocenter is a patient collimator located at 8 cm upstream of the

isocenter. Finally two, back and lateral, Philips Practics X-Rays tubes are mounted for the

verification of the treatment fields.

Inside CATANA collaboration particular care is going to be devoted to the

development of dosimetric techniques for the determination of absorbed dose in clinical

proton beams and 2D and 3D dose distribution reconstruction. A parallel-plate calibrated

Markus ionization chamber has been chosen as reference detector for the absolute dose

measurement, while gaf chromic and radiographic films, TLD (ThermoLuminescent

Detectors), natural diamond and silicon detectors are the choices for the relative one.

Depth dose curves and transverse dose distributions, either for the full energy and

modulated proton beams, are acquired with a water-tank system provided of three fully

computer-controlled step motors. This system, entirely developed at Laboratori Nazionali

del Sud, is controlled by a software providing the acquisition and dosimetric analysis of

data. Figure 6 shows a depth dose distribution peak in water obtained with the water-tank

system and Markus chamber for an unmodulated 25 mm diameter beam at the energy of

62 AMeV.

The Full Width at Half Maximum of the Bragg Peak is 2.76 mm while the 90-10 %

and 80-20% distal fall-off are 0.8 mm and 0.6 mm respectively. The entrance to peak

ratio is 4.72. We have realized, in collaboration with the Clatterbridge Center for

Oncology (UK), a set of wheel modulators to obtain a spread out therapeutic Bragg peak.

To do this various Bragg peaks, for different proton beam energies ranging from 62

AMeV to 10 AMeV, were acquired with the Markus chamber in the water phantom.

Proton beam energy lower than 62 AMeV are obtained inserting PMMA range shifters of

different thickness along the beam path. Finally Figure 7 shows the Spread Out Bragg

Peak obtained with the first prototype of the modulator wheel. Actually a first set of

modulator wheels (10, 12, 15, 20, 25 mm SOBP), developed for therapeutic purposes, are

available.

Even if CATANA should not be the clinical answer for all the Italian patients

affected by this kind of disease it represents the first successfully Italian example of the

collaboration between Nuclear and Medical Physicist together with Medical Doctors in

fighting tumours with hadrons. CATANA is the first milestone in Italy trough the

extensive use of hadrontherapy in cancer treatment.

Following this experience recently at LNS a new design of superconducting

cyclotron for medical applications has been proposed.. [12]. The design of the machine

model has been done to accelerate H

, He

, C

up to 250 MeV/amu,

corresponding to a maximum average field at extraction radius of 3.8 tesla. The

accelerators will be the core of a new proposed hadrontherapy center that should be

realized in Catania in the next years, mainly devoted to the treatment of deep sited

tumours with proton beams and to clinical studies of some particular tumoural form with

carbon ions.

6. ACCELERATOR BASED FACILITY FOR RADIOISOTOPES PRODUCTION.

Both Radioisotopes and enriched stable isotopes are essential to a wide variety of

applications in medicine, where they are used in the diagnosis and treatment of illness.

The radioisotopes produced for medical applications are tipically used in nuclear

medicine for diagnosis providing dynamic and functional information to study the organ

functions. The labelled biomolecules and radioisotopes involved should have as ideal

features the absence of beta particle emission, a half-life as short as possible and gamma

energy emission in a range between 100 and 300 keV. For a long period the production of

radioactive isotopes for medical applications was mainly based on neutron induced

nuclear reactions. This was essentially done in nuclear reactors but their availability is

slowly decreasing so that the accelerators based production facility are growing up. It is

well known and proven that Short life radioisotopes (Fluorine-18, carbon-11, Nitrogen-13

and oxygen

-15) are tipically accelerator produced radionuclides. Also others

Radionuclides (gallium-67, Indium-111, iodine-123, thallium-201) are produced by

means of 30 MeV cyclotrons for loco-regional distribution. According to those a wide

market of turn-key accelerators is nowadays available. The main choice in this field is

represented by cyclotrons. Infact looking to the time structure of the extracted beam,

cyclotrons represent the golden standard with respect to linacs. It si possible to state that

the power deposition in a production target is significantly better using a cyclotron which

it is characterized by a beam time structure that can be assumed as a “ practically

continuous beam”. Linacs are characterized by a low repetition rate so that the

instantaneous power deposition in the target so high that force to implement very

complex solution expecially in the material choice for thermal dissipation.

Even if it is possible to state that with a 30 MeV should be possible to produce

many radioisotopes of interest for medical application, it is growing the demand of

production of radionuclides requiring a primary proton energy at energy higher then 30

MeV like Magnesium-28, iron-52, germanium-68, strontium-82, xenon-122/127,

astanium-201. These demands are also forcing to try to use already existing high intensity

nuclear facilities that should be partially involved in this task.

Modern isotope production facilities consists of a compact H- cyclotron in the

nergy range between 10 and 30 MeV with extracted current up to 400 microA and highly

sophisticated target technology and chemistry. Target can be made solid, gas or liquid. In

any case they have to be designed in order to dissipate up to 10 kW. A temperature rise of

150 °C is well accepted. The choice of material is dependent on the particular nuclide

process. Although a general rule does not exist, there are some aspects of target body like

activation, contamination, corrosion and cooling, have to be kindly considered. Target

can be either internal and external, placed at the end of dedicated beam transport lines. In

tab. 1 the most common cyclotron produced radioisotopes for medical diagnostics are

reported.

Different commercial solutions are available. IBA, General Electric, CTI, EBCO

and SUMITOMO are the main cyclotron producers. They also offer dedicated

radiochemistry modules for the production of the labelled molecula to be used. A typical

production plant is reported in fig. 8

7. CONCLUSIONS

The role of particle accelerators is rising for medical applications. The synergy between

medicine (radiotherapy, radiology, nuclear medicine, oncology) and physics (nuclear and

accelerator physics) is growing even more and will represent the future challenge to get a

better quality of life in the third millennium. The number of potential patients for

hadrontherapy have been determined in many studies with different results [9,10,11]. It is

possible to state that the percentage of patients getting advantage with respect to

conventional radiotherapy is of the order of 30%. Moreover the exploitation of

accelerator based facility for the radioisotope production should significantly rise the

medical imaging performance permitting an early stage diagnosis of many important

diseases, first of all tumours. In conclusion we want to stress again as many advantage

can be carried out using particle accelerators for medical applications.

REFERENCE

[1]U. Amaldi, Nuclear Physics A654 (1999)375C-399C

[2]A.J.M. Vrmoken and F.A.T.M. Schermer (eds), Amsterdam, Oxford, Washnghton DC,

Tokyo: IOS press, (1994)

[3]S. Webb, IMRT, IOP 2001

[4]S. Webb, The physics of conformal radiotherapy, IOP 2001

[5]C. Van de Wiele, Int. J. Radiation Oncology Biol. Phys, Vol. 55 No1, pp5-15, 2003

[6]CAS Cern Accelerator school: Cyclotrons, linacs and their applications, CERN 96-02

[7] www.ptcog.web.psi.ch

[8]B. Gottshalck et al., Harvard Cyclotron Laboratory, report 3/29/89 (1989)

[9]Advances in Hadrontherapy, U. Amaldi, B. Larsson and Y. Lemoigne eds, Excerpta

Medica, 1996

[10]G. Gademan, ref [10], p.59

[11]R. Orecchia et al. Eur. J. Cancer (1998), p.459

[12] L. Calabretta, XXXV PTCOG Abstract, 2002

Tab. 1. List of some radioisotope tipically used for medical applications

Radioisot.

Nuclear

Reaction

Proton

Energy

(MeV)

Decay

Product

1/2

Emission

Application

N(p,n)

10→0

2.03m

PET

C(p,n)

10→0

9.96

min

PET

B(p,n)

10→0

20.38

min

PET

O(p,n)

16→3

109.8

min

PET

111

112

Cd(p,2n)

111

68 h

Radioim

mun

123

124

Xe(p,2n)

Cs→

123

Xe→

123

13.2 h

Brain

Spect

Zn(p,2p)

61.9 h

Radioim

mun

122

127

I(p,6

122

20.1 h

Father positron

emitter

122

nat

Ge(p,p

xn)

271 d

PET and

tumoral

marker

Fig

Fig. 1 Schematic view of a conventional LINAC (Courtesy by VARIAN)

Fig. 2 Photons, electrons and protons Depth Dose

Fig . 3 PSI Gantry

Fig. 4 – CNA: preliminary design of the CNA – Phase 1. The

synchrotron and the lines that serve three treatment rooms are

evidenced.

Figure 5. View of the CATANA beam line: 1.Treatment chair for patient

immobilization, 2. Final collimator, 3.Positioning laser, 4. Light field simulator; 5. A

Monitor chamber; 6. Intermediate collimator, 7-8.Boxes for the location of

modulator wheel and range shifter, 9.Proton beam output window.

0.5

1.5

2.5

3.5

4.5

0 5 10 15 20 25 30 35

Depth in water [mm]

Ionization [a.u.]

Figure 6. Bragg peak of 62 AMeV proton Beam acquired with a water-

tank system and a Markus chamber ionization chamber at CATANA

facility

100

110

0 5 10 15 20 25 30 35

Depth in water [mm]

Dose normalized at maximum value

[a.u.]

Figure 7 Spread Out Bragg Peak obtained with a modulator wheel;

Data acquired in water

Fig. 8 A typical PET center (courtesy by IBA)