Isotopes for future Nuclear Medicineuc.jinr.ru/3SummerSchool/Beyer4.pdfThe short-lived PET isotopes are based mainly on the (p,n) process, ~15 MeV is the preferable proton energy.

RADIOISOTOPES in

MEDICINE:Requirements - Production - Application

and future prospectives

4Isotopes for future Nuclear Medicine

Gerd-Jürgen BEYERProf.Dr.rer.nat.habil.(i.R.)

Geneva, Switzerland

THIRD INTERNATIONAL SUMMER STUDENT SCHOOL

NUCLEAR PHYSICS METHODS AND ACCELERATORS

IN BIOLOGY AND MEDICINE

Dubna, July 01-11, 2005

NUCLEAR MEDICINE 2005DIAGNOSIS THERAPIE

***

SPECT (SINGLE PHOTON EMISSION TOMOGRAPHY)

increase of diagnostic valuenew radiopharmaceuticalsdedicated instrumentation & quantification

***

PET AS RESEARCH TOOLMolecular in vivo biochemistryGene expressionClinical research

*

**

PET AS CLINICAL TOOLOncology Reimbursement of FDG-studiesNeurology Cardiology

-* -PET

*

Multi modality Imagingcombined SPECT(image of the year at the 46.SNM)Function and morphology

NEW APPROACHES IN RADIONUCLIDE THERAPY

* bio-selective antibodies(mab = monoclonal antibodies)

* bio-specific peptides(Octreotides, others)

* gene therapy* free chelators like EDTMP* Lyposomes* Nanoparticles

NEW RADIONUCLIDES for THERAPY

**

α-THERAPY & AUGER THERAPY

PET FOR IN VIVO DOSIMETRY***

metallic positron emitterslabelled drugsdose localization

G.BEYER (HUG, Geneva, 2005)

β - emittersα-emitters

( PET – CT )

Status 1998, USA only:

Health care totally ca. 1012 US$Surgery (50-100) • 109 US$Radiation (1-5) • 109 US$

Roy Brown : 107 nucl. med. examinations per year

Richard Reba: Isotope demand for therapy only1996 48 • 106 US$2001 62 • 106 US$2020 6000 • 106 US$

Résum é from the Medical Isotope Workshop, Dallas, May 2 -3, 1998

Future Demand for Demand for Isotopes in MedicineIsotopes in Medicine

Status 1998, USA only:

Health care totally ca. 1012 US$Surgery (50-100) • 109 US$Radiation (1-5) • 109 US$

Roy Brown : 107 nucl. med. examinations per year

Richard Reba: Isotope demand for therapy only1996 48 • 106 US$2001 62 • 106 US$2020 6000 • 106 US$

Résum é from the Medical Isotope Workshop, Dallas, May 2- 3, 1998

Future Demand for Demand for Isotopes in MedicineIsotopes in Medicine

CANCER

About 1 000 000 new cancer cases per year in EU (15)58 % local disease, 42 % generalized

45 % cured (5 year survival)

22 % surgery alone12 % radiation therapy6 % combination surgery + radiation5 % chemo-therapy

just beginning of systemic radionuclide therapy

HOW: expose cancer cells or cancer tissuewith sufficient radiation doses?

ISOTOPES in Therapy =ISOTOPES in Therapy =surgery with radiationsurgery with radiation

Tissue Tissue surgerysurgery

Cell Cell surgerysurgery

Molecular Molecular surgerysurgery

ISOTOPEISOTOPE

131131I, I, 9090Y, Y, 153153Sm,Sm,166166Ho, Ho, 177177LuLu

OthersOthersEEßß 1 1 –– 3 MeV3 MeV

212, 213212, 213 Bi, Bi, 211211At, At, 149149Tb,Tb,

223, 224223, 224RaRaEEαα 44––8 MeV8 MeV

125125II165165ErEr

EEee few eVfew eV

Range about 1 cm 30 – 80 µm 1 µm

ßß--KnifeKnife αα--KnifeKnife AugerAugerKnifeKnife

RIT = = RRADIOADIOIISOTOPESOTOPE TTHERAPYHERAPYor or RRADIOADIOIIMMUNOMMUNO TTHERAPYHERAPYor or systemic radionuclide therapysystemic radionuclide therapy

1936 32P against leukemia, J.H.Lawrence1939 89Sr uptake in bone metastases, C.Pecher1946 131I treatment of thyroid cancer, S.M.Seilin et al.1963 Radioactive colloides, B.Ansell et al1976 89Sr against pain from bone metastases, N.Firusian1978 Radiolabelled mab, D.Goldenberg1982 Treatment with 131I labelled mab, S.Larson et al.1990 Somatostatine receptor binding tracers, E.Krenning1993 89Sr, FDA approval 2000 FDA approval of 131I-CD20 against Lymphoma ?

Development of therpeuticals delayed

H.Mäcke, Basel

Control

Rats with SSR-positive tumours in livermodel mimics disseminated disease ⇒ PRRT

Int J of Cancer 2003177Lu-octreotate

(PRRT = Peptide Receptor Radionuclide Therapy )

Questions to be answered:

• Realtionship between radiation dose delivered to a leason and the therapeutic response

In vivo dosimetry by quantitative PET imagingIn vivo dosimetry by quantitative PET imagingneed for ßneed for ß++--emitting metallic radionuclidesemitting metallic radionuclides

• Relationship between beta – energy and therapeutic response

Variation of radionuclides with different ßVariation of radionuclides with different ß--energy energy need for metallic ßneed for metallic ß-- --emitters with very different emitters with very different energyenergy

ßß-- emitter emitter for for

therapytherapy

RIT

RITRIT = = RRADIOADIOIISOTOPESOTOPE TTHERAPYHERAPYor or RRADIOADIOIIMMUNOMMUNO TTHERAPYHERAPY

0.1

0.147

0.269

0.7

4.2

Range [mm] [keV][MeV]

softno9.4 d0.3169Er

interesting15980.4 h0.4/0.647Sc

Interesting18561.9 h0.4/0.667Cu

Not easy113/2086.7 d0.5177Lu

Most common(364keV)8.04 d0.8131I

Easy, carrier103 keV46.8 h0.8153Sm

Carrier13790.6 h1.1186Re

Palliation onlyno50.5 d1.589Sr

difficult(81 keV)26.8 h1.9166Ho

Difficult, generator155 keV17 h2.1188Re

Easy availableno64.1 h2.390Y

commentphotonsT ½EßmaxNuclide

10

8

6

4

2

0

144144Ce 319 keVCe 319 keV144144Pr 2998 keVPr 2998 keV169169Er 351 keVEr 351 keV177177Lu 498 keVLu 498 keV4747Sc 600 keVSc 600 keV

153153Sm 808 keVSm 808 keV143143Pr 934 keVPr 934 keV166166Ho 1855 keVHo 1855 keV

9090Y 2300 keVY 2300 keV

Beta spectraIn

tens

ity a

s %

bet

as p

er 1

keV

cha

nnel

0 1000 2000 3000 keV

Why metallic radionuclides?• 131I cannot fulfill all requirements (weak in vivo

stability)• We learnt to make bio-conjugates, that contain

chelating groups • Universality: the chelated bio-conjugates can be

labelled practically with any metallic radionuclide of group III and group IV elements

• The radiolabeled bio-conjugates are stable in vivo

• The bio-selective ligands are mainly monoclonal antibodies or peptides

ßß++ emitters emitters for for

in vivo dosimetryin vivo dosimetry

5 h p.i.

24 h p.i.

Patients:• 3 patients with metastases

of carcinoid tumor (histologically confirmed)

• No therapy with unlabeled somatostatin > 4 weeks

• Age: 46 – 67 years, male• All were candidates for

a possible 90Y-DOTATOC therapy

Scintigraphic abdominal images 5 & 24 h p.i.

affected by carcinoid with

extensive hepatic and paraaortal metastases.

[86Y]DOTA-DPhe1-Tyr3-octreotide

PET

[111In]DTPA-octreotide

SPECT

F.Rösch et.al.

Radiation doses for [90Y]DOTATOC therapy (based on [86Y]DOTATOC-PET)

Patient #1 Patient #2 Patient #3

Patient #1 Patient #2 Patient #3

Dtu

mor

(mG

y/M

Bq)

0

5

10

15

20

25

86Y-DOTATOC111In-DTPA-octreotide

Large discrepancies in tumor masses

H.Wagner Jr: A diagnostic dosimetric imaging procedure will be unevoidable a part of the protocoll for the

radioimmuno therapy (individual in vivo dosimetry).F.Rösch et.al.

Rare Earth Elements: Positron Emitters

43Sc 3.9 h 88 1.2 43Ca (p,n) 43Sc, 44Ca (p,2n) 43Sc

44Sc 3.9 h 94 1.544Ti decay (generator), 45Sc (p,2n) 44Ti

V, Ti (p,spall)

85mY 4.9 h 67 2.3 238 34 86Sr (p,2n) 85mY, ISOLDE

86Y 14.7 h 32 1.2637 33

1077 8386Sr (p,n) 86Y

ISOLDE

134Ce134Pr

75.9 h6.7 m

EC64 2.7

No605

Ta, Er, Gd (p,spall)132Ba (α,2n) 134Ce

138Nd138Pr

5.2 h1.5 m

EC76 3.4

No789 4

Ta, Er, Gd (p,spall)136Ce (α,2n) 138Nd, ISOLDE

140Nd140Pr

3.4 d3.4 m

EC50

2.4NoNo

Ta, Er, Gd (p,spall), ISOLDE141Pr (p,2n) 140Nd,

142Sm142Pm

72.4 m40.5 s

678

1.53.9

NoNo

Ta, Er, Gd (p,spall), ISOLDE142Nd (α,4n)142Sm

152Tb 17.5 h 20 2.8 DivTa (p,spall) ISOLDE

152Gd (p,4n) 149Tb, 142Nd(12C,5n)149Dy

Nuclide T ½ % ß+ MeV MeV γ / % Production Route

149Tb134Ce/La 140Nd/Pr

152Tb138Nd/Pr

Positron emitting radiolanthanides

PET phantom studies142SmEDTMP in vivo study

142Sm/Pm

ISOTOPES in Therapy =ISOTOPES in Therapy =surgery with radiationsurgery with radiation

Tissue Tissue surgerysurgery

Cell Cell surgerysurgery

Molecular Molecular surgerysurgery

ISOTOPEISOTOPE

131131I, I, 9090Y, Y, 153153Sm,Sm,166166Ho, Ho, 177177LuLu

OthersOthersEEßß 1 1 –– 3 MeV3 MeV

212, 213212, 213 Bi, Bi, 211211At, At, 149149Tb,Tb,

223, 224223, 224RaRaEEαα 44––8 MeV8 MeV

125125II165165ErEr

EEee few eVfew eV

Range about 1 cm 30 – 80 µm 1 µm

ßß--KnifeKnife αα--KnifeKnife AugerAugerKnifeKnife

αα--emitters emitters for therapyfor therapy

ALPHA EMITTERS FOR THERAPYALPHA EMITTERS FOR THERAPY

225225AcAc 10 d 233U decay chain 226Ra (p,2n) 225Ac229Th (α-decay) 225Ra

224Ra 3.66 d 228Th (α-decay) 224Ra223Ra 11.4 d 227Ac decay chain 226Ra (n,γ) 227Ac

227Th (α-decay) 223Ra213213BiBi 45.6 m 225Ac decay chain Ac–Bi generator

212Bi 60 m 224Ra decay chain Ra–Bi/Pb generator211211AtAt 7.2 h 209Bi (α,2n) 211At

149149TbTb 4.1 h4.1 h Ta (p,spall)Ta (p,spall)152152Gd (p,4n) Gd (p,4n) 149149TbTb

255Fm 20.1 h 255Ei (39.8 d)-decay 255Ei -255Fm generator

2 days later the mice have been devioded into 4 groups:

First in vivo experiment to demonstrate the efficiency of alpha

targeted therapy using 149Tb produced at ISOLDE, Summer 2001

0

10

20

30

40

50

60

70

80

90

100

0 20 40 60 80 100 120Survival time, days

% o

f sur

vive

d m

ice

Survival of SCID mice

5 MBq 149Tb, 5 µg MoAb

no MoAb

5 µg MoAb, cold

300 µg MoAb, cold

G.J.Beyer, M.Miederer, J.Comor et al. EJNM 2004, 31 (4), 547-554

103 d p.i. 108 d p.i.

300 µg mab cold 5 MBq 149Tb-mab (5 µg)

AUGER electronAUGER electronemitters emitters

for therapyfor therapy

165165ErEr

0 1000 2000 3000 Channel number

105

104

103

102

101

100

Cou

nts

per c

hann

el

LXHo

KX + KX

KXGe

KXHo165Er – 10.3 h

200 mm2 x 5 mm Ge(Li)

1

10

100

1000

6 8 10 12 14 16 18 20

Energy [MeV]C

ross

sec

tion

[mb]

• Only very few radionuclides exists that decay exclusively by EC-mode without any accompanying radiation

• 165Er is one of them• All labeling techniques used for

the three-valent radionuclides can be adapted without modifications.

• Generated in the EC-decay of the mother isotope 165Tm

• Production routes suitable for theTESLA accelerator:

(p,2n)

(p,n)

Yield:165Ho (p,n) 165Er

15 MeV p50 µA

5 h10 GBq

G. J. Beyer, S. K. Zeisler and D. W. Becker Radiochimica Acta 92 (4-6) , 219, 2004

Isotope Production with CyclotronsThe classical SPECT isotopes are produced via the (p,2n) process, the related p-

energy is ~25 MeVBecause of the continuous high demand of 201Tl, the (p,3n) is usually considered as a

main product. The upper p-energy for producing 201Tl is 30 MeV.The short-lived PET isotopes are based mainly on the (p,n) process, ~15 MeV is the

preferable proton energy. Normally dedicated small cyclotrons are used for PET. However, due to the high standard of targetry and production technology a large scale FDG-production can be integrated economically today into the program of a larger cyclotron, because of the low beam time demand.

New trends in radioimmuno therapy require alpha emitting nuclides. The 211At needs to be produced via the (α,2n) Process. The related α-energy is 28 MeV.

A cyclotron, that can accelerate alpha particles to 28-30 MeV can principally accelerate p to energies higher than 30 MeV. Consequently, higher reaction processes such as (p,4n) or generally (p,xn) or even (p,xn,yp) processes are possible. Such a multipurpose cyclotron with the option of high particle beam intensity and well developed tools for beam diagnosis and a certain variation of particle beam energy is an excellent universal instrument supporting commercial isotope production and R&D in the field of medical isotope application for diagnosis and therapy.

Commercial Isotope Productionwith cyclotrons

~30 MeV proton beam• 201Tl: 203Tl (p,3n) 201Pb 201Tl

most important SPECT isotope, commercialized by all radiopharmaceutical Co. The worldwide installed production capacity exceeds the demand

• 123I: 124Xe (p,2n) 123Cs 123I very important SPECT isotope, corresponding target design from Karlsruhe is installed worldwide. Batch size up to 10 Ci possible.

• 111In: 112Cd (p,2n) 111Inimportant for certain SPECT techniques, expensive because of low demand

• 67Ga: 68Zn (p,2n) 67Gaeasy to make, low and decreasing demand

IBA

201-Tl station

Target station for the production of 201Tl

with beam diagnosis elements and Automatic active target transport chain

Isotope Production with Cyclotrons(p,n) process with ~15 MeV protons

• 18F: 18O (p, n) 18F most important PET isotope, commercialized by many centers using dedicated small cyclotrons, however also done at 30 MeV or even at 65 MeV cyclotrons as well (Nice)

• 124I: 124Te (p,n) 124I very important PET isotope with commercial interest (in-vivo dosimetry), large scale production technology not yet available, same technology could be used for medium scale 123I production based on 123Te target material

• 86Y: 86Sr (p,n) 86Yvery important PET isotope with commercial interest (in-vivo dosimetry)

• 64Cu: 64Ni (p,n) 64Gaeasy to make, therapeutic isotope for RIT, PET allows the measurement of the biodistribution in sito.

• 186Re: 186W(p,n) 186Re186Re (3.7 d) is one of the two important therapeutic isotopes of Re. The advantage over 188Re (16 h) is the longer half-life, the advantage over the reactor based 185Re(n,γ)186Re process is the carrier free quality.

• Remark: The (p,n) process requires ~15 MeV only, and is performed normally at dedicated small PET cyclotrons. However, due to the high productivity of dedicated targets combined with a modern system for beam diagnosis allows to run these reaction under economical conditions at larger cyclotrons as well using only a small fraction of the available beam time.

COSTIS : Test Installationin Belgrade

COSTIS and its constructors at the low energy beam line of the mVINIS ECR ion source at

the TESLA Accelerator

Installation in Belgrade, Yugoslavia

COSTIS and its constructors at the low energy beam line of the mVINIS ECR ion source at

the TESLA Accelerator

Installation in Belgrade, Yugoslavia

Production of other useful isotopes with the PET cyclotron

Production of other useful isotopes with < 20 MeV proton induced reactions The irradiation of

solid materials requires much better beam quality parameters than gas targets. Consequently, beam homogenisation and beam manipulation is needed, ussually not possible at the PET cyclotrons.

External beam lines, known from classical isotope production at cyclotrons, will take this function over.

The new generation of multi-purpose cyclotrons will be equipped with high-tech diagnostic tools and provide higher beam current than in the past.

Auger Therapy20 GBqnatHo (p,n) 165Er10.3 h165Er

SPECT10 GBq123Te (p,n) 123I13.2 h123I

PET1 GBq124Te (p,n) 124I4.15 d124I

Therapy5 GBq186W (p,n) 186Re90.6 h186Re

PET10 GBq120Te (p,n) 120I1.35 h120I

PET5-10 GBq110Cd (p,n) 110In69.1 m110In

PET10 GBq94Mo (p,n) 94Tc4.9 h94Tc

PET, bioconjugates10 GBq90Zr (p,n) 90Nb14.6 h90Nb

PET, bioconjugates10 GBq89Y (p,n) 89Zr78.4 h89Zr

PET, bioconjugates5-10 GBq86Sr (p,n) 86Y14.7 h86Y

Generator, SPECT0.5-1 GBq82Kr (p,2n) 81Rb4.58 h81Rb/81mKr

PET2 GBq76Se (p,n) 76Br16 h76Br

PET10 GBq66Zn (p,n) 66Ga9.4 h66Ga

therapy, bioconjugates10-20 GBq70Zn (p,α) 67Cu61.9 h67Cu

PET & therapy, 40 GBq64Ni (p,n) 64Cu12.7 h64Cu

PET, encymes, vitamines0.5-1 GBqnatFe (p,2n) 55Co17.54 h55Co

PET: bioconjugates10-20 GBqnat.Sc (p,n) 45Ti3.08 h45Ti

ApplicationBatch sizeReactionT 1/2Isotope

Auger Therapy40 GBqnatHo (p,n) 165Er10.3 h165Er

SPECT20 GBq123Te (p,n) 123I13.2 h123I

PET2 GBq124Te (p,n) 124I4.15 d124I

Therapy20 GBq186W (p,n) 186Re90.6 h186Re

PET10 GBq120Te (p,n) 120I1.35 h120I

PET20 GBq110Cd (p,n) 110In69.1 m110In

PET20 GBq94Mo (p,n) 94Tc4.9 h94Tc

PET, bioconjugates20 GBq90Zr (p,n) 90Nb14.6 h90Nb

PET, bioconjugates20 GBq89Y (p,n) 89Zr78.4 h89Zr

PET, bioconjugates50 GBq86Sr (p,n) 86Y14.7 h86Y

Generator, SPECT20 GBq82Kr (p,2n) 81Rb4.58 h81Rb/81mKr

PET10 GBq76Se (p,n) 76Br16 h76Br

PET50GBq66Zn (p,n) 66Ga9.4 h66Ga

therapy, bioconjugates50 GBq70Zn (p,α) 67Cu61.9 h67Cu

PET & therapy, 100 GBq64Ni (p,n) 64Cu12.7 h64Cu

PET, encymes, vitamines50 GBqnatFe (p,2n) 55Co17.54 h55Co

PET: bioconjugates100 GBqnat.Sc (p,n) 45Ti3.08 h45Ti

ApplicationBatch sizeReactionT 1/2Isotope

PET-isotope production at

the IBA 30 MeV cyclotron:

Target stationat the end

of one beam line

equipped with 5 target ports

18F: H218O target

11C: N2-target15O: N2-target2 positions freeIBA

123-IODINE PRODUCTION ROUTES

123Cs 123Xe 123I5.9 min 2.08 hEC/ß+ EC

124I = 1 %125I < 1 %125I < 10-3 %22 – 28 MeV75 MeV p20 – 30 MeV p

124Te (p,2n)127I (p,5n)124Xe (p,2n)

1985Karlsruhe, Canada

1980 PSIWürenlingen

1975many places

ALTERNATIVES: local 123 I production using PET cyclotrons

123Te (p,n) 123 I 15 MeV p, 150 MBq/µAh

Fast, easy, reliable, clean product, suitable for direct labeling,

124I: 124TeO2 (p,n) 124I

124I T1/2 = 4.17 dß+ = 22.8 % Eßmax = 2.1 MeV

124I T1/2 = 4.17 dß+ = 22.8 % Eßmax = 2.1 MeV

R.J. Ylimaki, M.Y. Kiselev, J.J. Čomor, G.-J. Beyer

•DEVELOPMENT OF TARGET DELIVERY AND RECOVERY SYSTEM FOR COMMERCIAL

PRODUCTION OF HIGH PURITY IODINE-124

WTTC 10, Madison (USA), 2004

~13 MeV, 0.45 mCi/µAh 124I123I = 0.1 % EOB + 2 d

Pt-disc with 124TeO2 after irradiation

100 500 1000 1500 [keV]

511

124I

Pt-disc with 124TeO2 after irradiation

100 500 1000 1500 [keV]

511

124I

Pt-disc with 124TeO2 after irradiation

100 500 1000 1500 [keV]

511

124I124Iirradiation time: 1 h, 10 µA, protons

15 13 MeV 124I : (p,n) 250 150 MBq123I: (p,2n) 680 75 MBq

15 13 MeV 124I : (p,n) 250 150 MBq123I: (p,2n) 680 75 MBq

After 2 d: 178 / 51 MBq

86Sr (p,n) 86Y enriched 86SrO target, Pt-backing, ~15 MeV pelectrochemical separation technologyYield: 3.2 mCi/µAh with 13 MeV, [Rösch, 1990 ZfK-728]10 – 50 GBq possible

511 keV

Isotope Production with Cyclotrons

The (p,4n) process• 82Sr: 85Rb (p,4n) 82Sr

82Sr generates the short-lived 82Rb (80 sec), which is an positron emitter. This generator nuclide is used for PET in nuclear cardiology. The low availability and the still relatively high price hampered a larger distribution so far. Produced at TRIUMF(Ca), Protvino (Ru), South Africa and LosAlamos. Liquid Rb-metal sealed in silver bodies is used as target. High beam intensity is used.

• 52Fe: 55Mn (p,4n) 52Fe 52Fe is an interesting radionuclide for PET, it

generates the 20 min 52Mn daughter nuclide that can be used in PET.

• 149Tb: 152Gd (p,4n) 149Tb149Tb has shown its potential in TAT (targeted alpha therapy) as it is a partial alpha emitting nuclide and any bio-conjugate (monoclonal antibodies or peptides) can be easily labeled with this interesting nuclide

0 200 400 600 800 1000energy in keV

% b

etas

per

1 k

eV c

hann

el

2.0

1.5

1.0

0.5

0

52Mn

52Fe

ß+ from 52Fe - 52Mn55.0% 29.6%

0 200 400 600 800 1000energy in keV

% b

etas

per

1 k

eV c

hann

el

2.0

1.5

1.0

0.5

0

52Mn

52Fe

ß+ from 52Fe - 52Mn55.0% 29.6%

0 200 400 600 800 1000energy in keV

% b

etas

per

1 k

eV c

hann

el

2.0

1.5

1.0

0.5

0

52Mn

52Fe

ß+ from 52Fe - 52Mn55.0% 29.6%

52Fe 52Mn 52Crß+,EC ß+,EC8.3 h 21 m

52Fe 52Mn 52Crß+,EC ß+,EC8.3 h 21 m

Isotope Production with Cyclotrons

The (α,2n) process

• 211At: 209Bi(α,2n) 211At Among the very few suitable alpha emitting radionuclides for the 211At turns out to be the most suitable candidate for the medical application (targeted alpha therapy) presently a subject of intense international research activity.

The 211At can be produced by irradiating of natural Bi targets with 28 MeV alpha particles. Newly developed targets allow a production on large scale:

Production yield is ~ 40 MBq/Ah, production batches of 10 GBq are technically possible. A typical patient dose for therapy will range between 0.4 and 2 GBq.

0 1000 2000 30004000

Channel number

106

105

104

103

102

101

100

Cou

nts

per c

hann

el

211At (7.2h)207Bi (α,2n) 211At

28 MeV, ~20 MBq/µAh

indirect production routes

direct production routes

Segment of the decay chain A = 149Segment of the decay chain A = 149

ß+ ~ 7 %EC+ß+=

83 %

1

10

100

1000

10000

20 40 60 80 100 120

Incident particle energy (MeV)

Satu

rate

d yi

eld

(MB

q/ µA

)

Indirect production routesIndirect production routes 138138Ce(Ce(1616O,5n)O,5n)149149DyDy

136136Ce(Ce(1616O,3n)O,3n)149149DyDy

144144Sm(Sm(99Be,4n)Be,4n)149149DyDy152152GdGd ((αα,,77n)n) 149149DyDy

152152GdGd (p,(p, 4n)4n) 149149TbTb

16O

12C

142142Nd(Nd(1212C,5n)C,5n)149149DyDy

143143Nd(Nd(1212C,6n)C,6n)149149DyDy

9Be

4Hep

Higher Quality is requiredHigher Quality is required

Why is high specific activity that important?

• The receptor density is low for peptide ligands

• The infusion speed is limited for certain therapeutical approaches

• We do not wont to delute our biospecific ligands with inactive atoms

Influence of production mode for Influence of production mode for 177177Lu Lu 176176LuLu--route versus route versus 176176YbYb--routeroute

200 MBq 177Lu of NRG vs Nordion

0

25

50

75

100

0 0,5 1 1,5 2 2,5 3

nmol peptide

% in

corp

orat

ion

176Lu

176Yb

Factor of 4

Wouter A.P. BreemanErasmus MC Rotterdam

The Netherlands

200 MBq 177Luincubation:pH = 4.5

T = 80 oCT = 20 min

Peptide variation

Low carrier Low carrier –– shorter infusion timeshorter infusion time

• R&D needed for development of alternative technologies producing carrierfree radioisotope preparations for therapy.

• Reactor versus cyclotron production routes:185Re (n,γ)186Re // 186W (p,n) 186Re

67Cuothers

• Other alternatives:spallation reaction (CERN)isotope separation (of radioactive preparations)

mass number148 149 150 151 152

Surface IonizationTarget Ion Source

Plasma Ion Source

Radiolanthanides at

spallation or fission1 or 1.4 GeV protons

pulsed beam, 3 1013 p/pulse (~1µA)Ta-foil- or U-carbide target

Surface ionization ion source122 g/cm2 Ta (rolls of 25 µm foils)

at 2400 oCW-tube as ionizer at 2800oCRadioactive Ion Beams of

40 elements possible today

Alterantive Production Route:

high energy proton inducedSpallation Reaction

1 MW target for 1015 fissions per s

Hg-jet p-converter target

The SNS neutron source target station under construction

• Operating pressure 100 Bar• Flow rate 2 t/m• Jet speed 30 m/s• Jet diameter 10 mm• Temperature

- Inlet to target30° C

- Exit from target 100° C• Power absorbed in Hg-jet 1

MW• Total Hg inventory 10 t• Pump power 50 kW

The MEGAPIE 1MW molten PbBitarget under construction at PSI

Operation scheduled for 2006

What can nuclear centers do?

• Own specific medical isotope programs• Keep existing classical facilities running (211At)• Alternative ways for isotope production• High-tech radiochemistry• Integrate physical methods into the isotope

programs (mass separation for example)• Collaboration with bio-chemistry and medicine

(oncology, radiology, nuclear med.)• International collaboration and integration into

existing research network

G.Beyer, PLSRNC-1, Varna (Bulgaria) 21-27 Sept. 2003