Chapter Radioisotopes

Marie-Claire Cantone (I) convenerAri Jokinen (FIN) NuPECC liaisonFerid Haddad (F)Sotirios Harissopoulos (GR)Mikael Jensen (DK)Itzhak Kelson (IL) Ulli Köster (F) convenerOndrej Lebeda (CZ)Bernard Ponsard (B) Uli Ratzinger (D)Thierry Stora (CH)Ferenc Tarkanyi (HU)Piet Van Duppen (B) NuPECC liaison

Introduction

1. Properties of (present and future) radioisotopes for nuclear medicine

2. Production methods and facilities

3. Specific issues

Radio-nuclide

Half-life (h)

Eγγγγ(keV)

γIntensity(%)

Decay type

Ga-67 7893

1854221 EC

Kr-81m 0.004 190 64 IT

Tc-99m 6 141 89 IT

In-111 67171245

9194 EC

I-123 13 159 83 EC

Xe-133 126 81 38 ββββ-

Tl-201 7370

1675910 EC

I-131 192 364 82 ββββ-

Lu-177 161113208

610 ββββ-

SPECT isotopes

PET isotopes

Radio-nuclide

Half-life (h)

Intensity β+

(%)E mean (MeV)

Range (mm)

C-11 0.34 99.8 0.39 1.3

N-13 0.17 99.8 0.49 1.8

O-15 0.03 99.9 0.74 3.2

F-18 1.83 96.7 0.25 0.7

Ga-68 1.13 89.1 0.83 3.8

Rb-82 0.02 95.4 3.38 20

Longer-lived PET isotopes

Radio-nuclide

Half-life (h)

Intensityβ+ (%)

E mean (MeV)

Range (mm)

Sc-44 3.97 94.3 0.63 2.5

Cu-64 12.7 17.6 0.28 0.8

Br-76 16.2 55 1.18 6

Y-86 14.7 31.9 0.66 2.6

Zr-89 78.4 22.7 0.40 1.4

I-124 100 22.8 0.82 3.8

What about PET with a ββββ- emitter?

Isotopes for 3-photon -cameras

Radio-nuclide

Half-life (h)

B.R. β+

(%)E mean (MeV)

Range (mm)

E γγγγ(keV)

Intensity γγγγ

Cl-34m 0.53 54.3 0.84 3.9 2127 43

Sc-44 3.97 94.3 0.63 2.5 1157 100

Mn-52 134 29.6 0.24 0.77449361434

9195

100

Y-86 14.7 31.9 0.66 2.662810771153

338331

Tc-94 4.9 10.5 0.36 1.1703850871

10096

100

Tc-94m 0.87 70.2 1.07 5.2 871 94

I-124 100 22.8 0.82 3.8 603 61

gammarays

SPECTcamera

beta rays

500x

alpha rays

50000x

5x

Auger electrons

cancer cells

chromosome

tumor

The nuclear medicine alphabet

Beta therapy isotopesRadio-nuclide

Half-life (d)

Eβmean(MeV)

Rangemean (mm)

Eβmax

(MeV)

Rangemax (mm)

Eγγγγ

(keV)

Iγγγγ

(%)

P-32 14.3 0.7 3 1.71 9.1 -

Sr-89 50.6 0.59 2.3 1.5 7.8 -

Y-90 2.67 0.93 4.4 2.28 12 -

I-131 8.03 0.18 0.39 0.81 3.7284364637

6.181.57.2

Sm-153 1.94 0.22 0.55 0.81 3.7 103 29.3

Ho-166 1.12 0.67 2.8 1.85 10 81 6.6

Lu-177 6.65 0.13 0.23 0.50 1.9 113208

6.210.4

Er-169 9.39 0.10 0.14 0.35 1.1 -

Re-186 3.72 0.35 1.1 1.07 5.2 137 9.5

Re-188 0.71 0.76 3.3 2.12 12 155 15.6

Radio-nuclide

Half-life

Daugh-ters

Half-life

Cumulativeαααα/decay

Eαααα mean(MeV)

Range(µµµµm)

Tb-149 4.1 h 0.17 3.97 25

Pb-212 10.6 hBi-212Po-212

1.01 h0.3 µs

1 7.74 65

Bi-212 1.01 h Po-212 0.3 µs 1 7.74 65

Bi-213 0.76 h Po-213 4 µs 1 8.34 75

At-211 7.2 h Po-211 0.5 s 1 6.78 55

Ra-223 11.4 d

Rn-219Po-215Pb-211Bi-211

4 s1.8 ms0.6 h130 s

4 6.59 >50

Ra-224 3.66 d

Rn-220Po-216Pb-212Bi-212

56 s0.15 s10.6 h1.01 h

4 6.62 >50

Ac-225 10.0 d

Fr-221At-217Bi-213Po-213

294 s32 ms0.76 h4 µs

4 6.88 >50

Metabolic targeting

Thyroid cancer123I- for imaging131I- for therapy

Bone metastases1.5 million patients world-wide

99mTc-MDP for SPECT imaging18F- for PET imaging

Therapy153Sm-EDTMP (Quadramet)89Sr2+ (Metastron)223Ra2+ (Xofigo/Alpharadin)

Receptor Targeted Therapies

Roelf Valkema, EANM-2008.

ImmunologyStructural biology

Coordination chemistry

Nuclear physics and

radiochemistry

Target

Receptor Radionuclide

LinkerPeptide, antibody, etc.

Introduction

1. Properties of (present and future) RI for NM

1.1. RI for imaging1.1.1. gamma emitters for SPECT and planar imaging1.1.2. positron emitters for PET

1.2. RI for therapy1.2.1. gamma emitters (brachytherapy)1.2.2. beta emitters1.2.3. alpha emitters1.2.4. Auger electron emitters1.3. Radiotracers for biokinetics and pharmaceutica l R&D

2. Radioisotope Production

Accelerators

Accelerator types

Ion A Q Cyclotron Tandem LINAC

K=20 MeV Uterm=10 MV Ueq=20 MV

p 1 1 20 MeV 20 MeV 20 MeV

d 2 1 10 MeV 20 MeV 20 MeV4He 4 2 20 MeV (30 MeV) 40 MeV6Li 6 3 30 MeV 40 MeV 60 MeV12C 12 6 60 MeV 70 MeV 120 MeV

heavier projectilesRadio-nuclide

Target Reaction Projectile Energy(MeV)

F-18 O-16 (α,pn)&(α,2n) 4He 40

Sc-43 Ca-40 (α,n) 4He 24

Sc-44m Ca-44 (d,2n) d 30

Cu-61 Co-59 (α,2n) 4He 40

Cu-64 Ni-64 (d,2n) d 30

Cu-67 Ni-64 (α,p) 4He 40

In-111 Ag-109 (α,2n) 4He 40

Sn-117m Cd-116 (α,3n) 4He 42

At-211 Bi-209 (α,2n) 4He 29

Rn-211 Bi-209 (6Li,4n) 6Li 50-60

2. Production methods and facilities

2.1. Reactions2.1.1. (n,gamma)2.1.2. fission2.1.3. proton induced reactions2.1.4. light ion induced reactions2.1.5. other 2.1.6. generators

2.2. Facilities2.2.1. research reactors2.2.2. accelerators2.2.3. importance of targetry

3. Specific issues

3.1. examples of success of NM applications versus conventional (non-nuclear) treatments

• “Impact” of PET and SPECT imaging in treatment decisions.• Statistics on success of 131I thyroid treatments.• Survival benefit, fractions of complete or partial response and

quality-of-life for lymphoma patients treated with BEXXAR, ZEVALIN, 131I-rituximab and 177Lu-rituximab versus conventional treatments with references.

• Survival benefit, fractions of complete or partial response and quality-of-life for GEP-NET patients treated with 90Y/177Lu-DOTA-TOC/DOTA-TATE.

• Survival benefit, fractions of complete or partial response and quality-of-life for patients with bone metastases treated with Metastron, Quadramet or Xofigo.

• Something on SIRspheres and THERASPHERES?

Roelf Valkema, EANM-2008.

Roelf Valkema, EANM-2008.

The chart of nuclides – nuclear medicine perspective

18F11C

68Ga99mTc

201Tl

111In

67Ga

133Xe

131I90Y89Sr

153Sm

123I

186,188Re177Lu

SPECTPETTherapy

“exotic” isotopes

3.2. statistics of RI use in Europe: evolution and trends

3.3. 99mTc supply, alternative production methods, European prospects

Cardiolite 8 mSv201Tl 41 mSv

15 M*33 mSv ≈≈≈≈500000 Sv/a

collective dose

cf. 1000 Sv/a fromnuclear industry

The economy of nuclear medicine and the aviation in dustry

“Fuel” sourcing

“Fuel” refinement

Equipment(amortization, maintenance,leasing, chartering)

Personal costs

0.1%(0.26€)

0.8%(1.98€)

245.61€ (NEA, 2008)

19%

5%

17%

31%

Eff

ect

Dose

Therapeutic effect

Side effects

Eff

ect

Dose

Therapeutic effect

Side effects

Acceptable side effects

Acceptable side effects

High selectivity is essential to widen the therapeutic window!

Paracelsus (1493-1541)“All things are poison and nothing is All things are poison and nothing is All things are poison and nothing is All things are poison and nothing is

without poison. Only the dose makes without poison. Only the dose makes without poison. Only the dose makes without poison. Only the dose makes

that a thing is not poisonous.”that a thing is not poisonous.”that a thing is not poisonous.”that a thing is not poisonous.”

Septem Defensiones 1538, Vol. 2.

3.4. Theranostics, “matched pairs”

Theranostics

Eff

ect

Dose

Therapeutic effect

Side effects

Acceptable side effects

Accurate dosimetry is essential for optimum use of the therapeutic window.

Theranostics

Eff

ect

Dose

Acceptable side effects

Accurate dosimetry is essential for optimum use of the therapeutic window.

Terbium: a unique element for nuclear medicine

3.5. 177Lu, a showcase for nuclear physics and radiochemistry

Waste problem for hospitals!R. Henkelmann et al., Eur. J. Nucl. Med. Mol. Imag. 36 (2009) S260.

Alternative production route to 177Lu

• Free of long-lived isomer• Non-carrier-added quality• “Needs” high-flux reactor

The rising star for therapy

3.7. joint exploitation of accelerators for NP rese arch & RI production

Diagnostic Accuracy: PET vs SPECT

Bateman et al, J Bateman et al, J NuclNucl CardiolCardiol 20062006

81

66

76

86

10091

0

20

40

60

80

100

Sensitivity Specificity Accuracy

SPECTPET

** ** **p<0.001p<0.001

%%

(source : DOE, USA)

82Rb is used for PET in cardiology���� 82Sr/82Rb generator

Facilities producing Sr-82 in the world

LANL, USA – 100 MeV, 200µA

BNL, USA – 200 MeV, 100µA

INR, Russia – 160 MeV, 120µA

iThemba, South Africa – 66 MeV, 250µA

TRIUMF, Canada –110 MeV, 70 µA

BLIP

Facilities producing Sr-82 in the world

LANL, USA – 100 MeV, 200µA

BNL, USA – 200 MeV, 100µA

INR, Russia – 160 MeV, 120µA

iThemba, South Africa – 66 MeV, 250µA

TRIUMF, Canada –110 MeV, 70 µA

ARRONAX, France – 70 MeV, >100 µA

BLIP

3. Specific issues3.1. examples of success of NM applications versus

conventional (non-nuclear) treatments3.2. statistics of RI use in Europe: evolution and trends3.3. 99mTc supply, alternative production methods,

European prospects3.4. dosimetry: typical doses of imaging procedures ,

Theranostics, “matched pairs”3.6. applications of NP technologies for RI product ion

(history, present, future)3.7. joint exploitation of accelerators for NP rese arch & RI

production3.8. promising new radioisotopes and their present supply

limitations

Paracelsus (1493-1541)““““Many have said of Alchemy, Many have said of Alchemy, Many have said of Alchemy, Many have said of Alchemy,

that it is for the making of gold that it is for the making of gold that it is for the making of gold that it is for the making of gold

and silver. For me such is not and silver. For me such is not and silver. For me such is not and silver. For me such is not

the aim, but to consider only the aim, but to consider only the aim, but to consider only the aim, but to consider only

what virtue and power may lie what virtue and power may lie what virtue and power may lie what virtue and power may lie

in medicines.”in medicines.”in medicines.”in medicines.”

(Edwardes)

500 years later:“Many have said of nuclear physics, that it is for the making of gold and silver (and other elements’) isotopes.For us such is not the only aim, but alsoto consider what virtue and power may lie in it for medicine.”

Open questions

• Layout• Fix chapter/section numbering for cross-references• Conventions: 99mTc or Tc-99m?• Abbreviations at occurrence or in glossary?• “Anecdotes” in each section or as “abstract”?• “Professional” graphs• Copyright requests

• Implication of physicians