MEDICIS-PROMED final conference, Erice, 2nd€¦ · Erice, 2nd May 2019 Michele Ballan 6 pair pair...

Dr. Michele BallanINFN-LNL

[email protected] behalf of the SPES-ISOLPHARM group

MEDICIS-PROMED final conference, Erice, 2nd May 2019

Michele BallanErice, 2nd May 2019 2

Introduction: ISOLPHARM @ SPES ISOL facility

Production target development

Beam development

Collection target development


at the heart of SPES: the cyclotron (70 MeV 0,75 mA p+)

and related infrastructure.

the ISOL facility and the acceleration of neutron-rich

unstable nuclei.

production of radionuclides for applications.

multidisciplinary neutron sources.

1. A second generation (for neutron-rich radioactive ion beams)

2. An interdisciplinary (for p,n applications)is:


The ISOLPHARM method for the production of radiopharmaceuticals is a INFN PATENT

Patent title:«Method for producing beta emitting radiopharmaceuticals

and beta emitting radiopharmaceuticals thus obtained»

Flexible production, high specific activity & radionuclidic purity

More information on Dr. Alberto

Andrighetto’s talk

More information on Marianna

Tosato’s poster


Diagnostic isotopes Therapeutic isotopes

Among the wide set of ISOL producible nuclides, almost 60 show relevant properties

for medicine, in terms of half-life, decay radiationand chemical behavior

Theragnostic isotopes


pair pair

pair

pair

Diagnosis Therapy Theragnostics

Early feasibility studies were focused on state-of-art radionuclides:

ISOLPHARM true potential can be expressed if innovative/less available nuclides are considered

67Cu111Ag

43Sc

152Tb 155Tb149Tb

47Sc

64Cu

• t½: 233 min• 100% β+/ϵ (PET)

• t½: 12.701 h• 38,5% β- (191 keV av.)• 61,5% β+ (PET)

• t½: 2.58 d• 100% β- (162 keV av.)

• t½: 7.45 d• 100% β- (360 keV

av.)

• t½: 3.4 d• 100% β- (162 keV av.)

• t½: 4.12 h• 16.7% α (3.97 MeV)

• t½: 17.5 h• 100% β+/ϵ (PET)

• t½: 5.32 d• 100% β+/ϵ (SPECT)

F. Borgna et al., Appl. Radiat. Isot., 2017


𝑌 = 𝜎Ф𝑁𝜀𝑑𝜀𝑒𝜀𝑖𝜀𝑡𝜀𝑟

Producible Yield with ISOL:To be estimated in order to

evaluate the feasibility of the production of the selected nuclide with ISOLPHARM

In-target yield:Can be calculated with dedicated MC codes as

FLUKA and Geant4

Diffusion/Effusion efficiencies:Difficult to estimate, but generally

high for long-lived medical isotopes (unless chemical issues)

How much can we produce with the ISOLPHARM method?

Ionization efficiency:Can be experimentally determined at the

offline laboratories at LNL using stable isotopes of the element of interest

Beam transport efficiency:Generally known, it ranges

between 80% and 90%

Recovery efficiency:Can be experimentally

determined similarly to the ionization efficiency




1. Identify the suitable target material that has to be:• Solid Safety requirement at SPES• Refractory ISOL requirement• Porous to promote the release

2. Calculate the yields with MC codes

3. Experimentally verify the yields Compare the results with different MC codes


40 MeV 200 μA Proton beam on SPES UCx target

FLUKA MC results were already compared with other MC codes (A. Monetti et al., Eur. Phys. J. A, 2015 ) and with experimental test at ORNL facility (D. Scarpa et al., Eur. Phys. J. A, 2011)


X [cm]

Y [c

m]

[p+/cm2]

1

X

Y Z

Analisi elettrotermica_proton beam max raffr

25.8839271.73

517.576763.423

1009.271255.12

1500.961746.81

1992.652273.62

DEC 3 2014

23:32:29

NODAL SOLUTION

STEP=1

SUB =123

TIME=3000

TEMP (AVG)

RSYS=0

SMN =25.8839

SMX =2273.62

1

X

Y Z

Analisi elettrotermica_proton beam max raffr

25.8839271.73

517.576763.423

1009.271255.12

1500.961746.81

1992.652273.62

DEC 3 2014

23:32:29

NODAL SOLUTION

STEP=1

SUB =123

TIME=3000

TEMP (AVG)

RSYS=0

SMN =25.8839

SMX =2273.62

[°C]

IT = 700 A

IIS = 200 A

Desgined for stopping a 40 MeV 200 µA PPB (FLUKA)

Desgined for working temperaturesabove 2000°C (ANSYS®)

Tested and commissioned for high temperature operation


70 MeV 100 μA Proton beam on ZrGe target


1.00E+02

1.00E+03

1.00E+04

1.00E+05

1.00E+06

1.00E+07

60 61 62 63 64 65 66 67 68 69

Yiel

ds

[par

t/s]

Mass Number [amu]

Copper isotopes yields - 70 MeV 100 μA protons on ZrGe target

FLUKA Bertini BIC INCL++

0

2

4

6

8

10

12

0 10 20 30 40 50 60 70 80 90 100

Cro

ss s

ect

ion

[m

b]

Energy [MeV]

natGe(p,X)64Cu cross section

TALYS mod TALYS default TENDL 2015 PEANUT FLUKA

0.0

0.5

1.0

1.5

2.0

2.5

3.0

0 10 20 30 40 50 60 70 80 90 100

Cro

ss s

ect

ion

[m

b]

Energy [MeV]

natGe(p,X)67Cu cross section

TALYS mod TALYS default TENDL 2015 PEANUT FLUKA

• High variability of the results• Lack of experimental measurements


40 MeV 200 μA Proton beam on TiC target

1.00E+00

1.00E+01

1.00E+02

1.00E+03

1.00E+04

1.00E+05

1.00E+06

1.00E+07

42 44 46 48 50

Yiel

ds

[par

t/s]

Mass Number [amu]

Scandium isotopes yields - 40 MeV 200 μA protons on TiC target

FLUKA BERT BIC INCL++


70 MeV 100 μA Proton beam on GdB4 target

1.00E+00

1.00E+02

1.00E+04

1.00E+06

1.00E+08

146 151 156 161

Yiel

ds

[par

t/s]

Mass Number [amu]

Terbium isotopes yields - 70 MeV 100 μA protons on GdB4 target

FLUKA BERT BIC INCL++


Time Nuclei Nuclei Nuclei Nuclei

[days] [Bq] [Ci] [#] [Bq] [Ci] [#] [Bq] [Ci] [#] [Bq] [mCi] [#]0.5 5.70E+10 1.54 1.15E+15 2.48E+10 0.67 1.04E+16 2.66E+10 0.72 1.75E+15 2.37E+08 6.40 7.61E+13

1 6.37E+10 1.72 1.29E+15 4.72E+10 1.28 1.97E+16 4.03E+10 1.09 2.66E+15 4.44E+08 11.99 1.43E+14

1.5 6.45E+10 1.74 1.30E+15 6.74E+10 1.82 2.81E+16 4.75E+10 1.28 3.13E+15 6.24E+08 16.87 2.01E+14

2 6.46E+10 1.75 1.30E+15 8.56E+10 2.31 3.57E+16 5.12E+10 1.38 3.38E+15 7.82E+08 21.15 2.52E+14

3 6.46E+10 1.75 1.31E+15 1.17E+11 3.16 4.87E+16 5.42E+10 1.46 3.57E+15 1.04E+09 28.14 3.35E+14

4 6.46E+10 1.75 1.31E+15 1.42E+11 3.84 5.93E+16 5.50E+10 1.49 3.62E+15 1.24E+09 33.49 3.99E+14

5 6.46E+10 1.75 1.31E+15 1.63E+11 4.40 6.78E+16 5.52E+10 1.49 3.64E+15 1.39E+09 37.58 4.47E+14

Time Nuclei Nuclei Nuclei Nuclei

[days] [Bq] [Ci] [Nuclei] [Bq] [Ci] [#] [Bq] [Ci] [#] [Bq] [Ci] [#]0.5 9.46E+09 0.26 8.78E+15 3.16E+10 0.85 6.76E+14 4.26E+11 11.51 3.87E+16 1.43E+11 3.86 9.48E+16

1 1.92E+10 0.52 1.78E+16 3.58E+10 0.97 7.67E+14 6.92E+11 18.70 6.29E+16 2.77E+11 7.49 1.84E+17

1.5 2.85E+10 0.77 2.65E+16 3.64E+10 0.98 7.79E+14 8.57E+11 23.17 7.79E+16 4.02E+11 10.88 2.67E+17

2 3.74E+10 1.01 3.47E+16 3.65E+10 0.99 7.80E+14 9.60E+11 25.95 8.73E+16 5.20E+11 14.06 3.45E+17

3 5.40E+10 1.46 5.02E+16 3.65E+10 0.99 7.81E+14 1.06E+12 28.75 9.67E+16 7.33E+11 19.82 4.86E+17

4 6.92E+10 1.87 6.42E+16 3.65E+10 0.99 7.81E+14 1.10E+12 29.83 1.00E+17 9.21E+11 24.89 6.11E+17

5 8.29E+10 2.24 7.70E+16 3.65E+10 0.99 7.81E+14 1.12E+12 30.25 1.02E+17 1.09E+12 29.33 7.20E+17

47Sc

Activity Activity

SPES UCx target GdB4 target, 70 MeV 100 μA p+ beam

TiC/TiB2 target, 40MeV 200 μA p+ beam ZrGe target, 70MeV 100 μA p+ beam64Cu 67Cu

Activity Activity

43Sc

Activity Activity Activity

111Ag

Activity

149Tb 152Tb 155Tb




A. Target-Ion source

unit

B. First triplets and steers and

Diagnostic Box 1C. Wien Filter

D. Diagnostic Box 2 and slits

E. Second triplets

F. Secondary target station


107Ag 109Ag

65Cu

63Cu

Test number Efficiency

[#] [%]

1 8.03E+00

2 8.75E+00

3 6.23E+00

Average 7.67E+00

Copper ionization tests - efficiency


45Sc 159Tb 159TbO

Very low ionization efficiency for Sc and Tb!Other techniques may solve this issue, such as:• Photoionization• Molecular beamsTests ongoing

Test number Efficiency

[#] [%]

1 0.32

2 0.30

3 0.14

Average 0.25

Scandium ionization tests - Efficiency




1 cm

NaCl substrate

63Cu

NaCl substrateNaNO3 substrate

107Ag

109Ag

45Sc65Cu

1 cm 1 cm

Recovery efficiency: ~ 77% Recovery efficiency: ~ 50% Recovery efficiency: under developmentF. Borgna, M. Ballan et al., Molecules, vol. 23, no. 10, 2018


Dedicated production target were developed. SPES Facility is still under construction, so it was not possible to test and validate all target concepts, consequently a campaign of MC simulations was carried out.

The ISOLPHARM method (patent deposited) has the capability to flexibly produce radiopharmaceuticalprecursors with high specific activity using a proton beam ad intermediate energies.

Experimental activities were performed with stable beams, and thecapability to ionize and collect the stable counterparts of the desirednuclei has been proved.

Some radionuclides (as 111Ag , 67Cu, etc) that are extremely interesting and could be used as precursors fornew radiopharmaceuticals, cannot be easily produced with state-of-art techniques.

First radionuclides of medical interest for research (small quantities) will be opportunely collected when thefirst SPES RIB will be delivered.

MEDICIS-PROMED final conference, Erice, 2nd€¦ · Erice, 2nd May 2019 Michele Ballan 6 pair pair...

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