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