with a special view on the need for ISOLDE and other big science facilities Mikael Jensen Professor Applied Nuclear Physics Hevesy Lab Risø Risø DTU Campus Technical University of Denmark ID: 792261
Download The PPT/PDF document "Medical Isotope Production and Use" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Medical Isotope Production and Use-with a special view on the need for ISOLDE and other big science facilities
Mikael JensenProfessor , Applied Nuclear PhysicsHevesy Lab - Risø- Risø-DTU CampusTechnical University of Denmark Presented atISOLDE 50th Anniversary WorkshopCERN- December 2014
DTU-NUTECH
Slide2Center for
Nuclear
Technologies
Radioecology
Isotope researchRadiation physics
RadiopharmaceuticalsRadiobiologyRadiation TherapyTargets
Former Risø-
an ancient National Laboratory for Reactor Research, then ”Sustainable Energy”
Slide3My background:The Hevesy Laboratory-Medical use of accelerators
Isotope productionRadiation therapyGeorge Hevesy 1885-1966
Slide45.5 MeV protons 1938
Early Isotope Separation on Line – 55 years ago
Slide5Isolde – Master of the Isotopes
Slide6Slide7Application of Radioactive Isotopes:MEDICAL !
“I must confess that one reason we have undertaken this biological work is that we thereby have been able to get financial support for all of the work in the laboratory. As you know, it is much easier to get funds for medical research.”
—Lawrence to Niels Bohr, 1935
Slide8Why Radioactive Materialsfor
injection into fellow living beings in 2014 ?
59
years
post Hiroshima,
28 years post Chernoby, …….Fukushima still in clear memory !
Slide9Nuclear Medicinein vivo use
of radioactivityIsotope uptake, dilution, excretion, Whole Body CountingDiagnostic = Gamma camera
, SPECT and PET
Therapeutic
= Radionuclide Therapy”The magic bullet”Non invasiveCheapInternational = Atoms for Peace, IAEA….
Slide10The LegacyTechnology PUSHED from the National Laboratories or Big Science
Cyclotron and artificial radioactivity RadiochemistryScintillation countersAnger CameraMo-99/ Tc-99m generatorPET CameraF-18 FDGIsotopes far from
stability
line
… (no medical pull of technology) !
Slide11Diagnostic Nuclear Medicine
Functional Metabolic MolecularRequiring
higher
s
pecificactivity
O-15 waterF-18 DOPA
Slide12High specific activity
A historical development: from 1913 ”indicators, and 1930 ”tracers”To ligands, radiometals for late stage chelation, radioactive
antibodies
and
antibody fragmentsRequires : transmutation or very effective Slizard-Chalmers or hot atom isotope separatorsTBq / uMol
Slide13Halflife- DiagnosticLong
enough to circulate and localizeShort enough to keep radiation dose low Logistics of production, transport and labelling
The generators:
Mo-99/Tc-99m (Gamma
Camera +SPECT)Rb-81/Kr-81m (Gamma Camera +SPECT)Ge-68/Ga68 (PET)Sr-82/Rb82+ Some more…200 secs-3 days
Mother isotopes must be produced somewhere
Slide14Halflife - Therapeutic
Most of dose to be delivered when optimal
uptake
has
taken placeT½ < Cell cycle life of target tissue
Slide15The clinical problemNuclear
medicine is about routine useOur isotope is part of a pharmaceuticalRequires clinical trials and proof of merritGMP, Safety and
Efficacy
Costly
, slow, highly regulated
Slide16GMP is the
opposite ofResearch
Slide17Preclinical
- or
Small
animal
imaging:Solution or Problem ?
Slide18F-18 Fluoride
F-18
Fluoro
Choline
”fastest growing medical technology ever….”PET-CT, a problem ?
Slide19The problem of economics and scale
Very few (if any) radiopharmaceuticals can carry the full cost of development, registration and post
market
maintenance Many radiopharmaceuticals are orphanA clinical market should be served evenly across nations and territoriesNo gaps in availability But the cost of the radiopharmaceutical is a surprisingly small part of total cost of a given procedure
Slide20Isotopes for nuclear medicine
from where ? (1)
Neutron
rich
: by fission or neutron capture
Present generation of research
reactors
getting
old and
retiring
. Acces to
high
flux
, long time and transport
difficult
.
Access to HEU
getting
difficult
Slide21A Mo-99 supply crisis:
In October 2016 NRU in Chalk River, Canada closesIs it a North American Problem?No realistic replacements still in sight Much talk and many Klondyke efforts
Possible
results:Migration to CT and MRIMigration to PET A role for Ga-68 ?Worldwide loss of Nuclear Medicine infrastructureMay have effects on other isotopes as wellUnderlying cause : Goverment neutrons have been too cheap !
Slide22Isotopes for nuclear medicine
from where ? (2) (p,xn) from Cyclotrons, mostly
About
11
MeV C-11,N-13,O15,F-18 for local use
16-18 MeV F-18 for distribution, all (p,n) products30 MeV (p,2n) products, high yield In-111, Ga-67, I-12370-100 MeV Sr-82, Ge-68 (shortage) Goverment Linacs
Slide23natural decay chains
nuclear fuel / weapons cycle spallation accelerators - (At-211)Perhaps via generators , mother isotope from
natural decay chains
nuclear fuel / weapons cycle
spallation acceleratorsAlpha emitters for nuclear medicine from where ? Fast growing interest beacuse of Ra-223 chloride (Alpharadin
)
Slide24The cottage industry of small cyclotrons
16-18 MeV enough for F18 and the PET radiometals (Cu-64, Ga-68, Zr-89 )Theraputic doses can be
made (Er-165)
Tc-99m is
possible in limited amountsLogistics more simpleCheap infrastructureFlexibleLead time for changes smaller
Slide252013 PT 600 prototype, Hevesy Lab
”Point of demand” produktionA 7.8 MeV cyclotronF-18C-11N-13 perhapsGa-68 YES !
Coffee
makers ?(remember to add 10 t neutron shield)
Slide26α, β- and Auger radiation
26
Slide27Microinjection of cells in culture
27
Slide28Direct injection28
Slide29Slide3030
Claus E. Andersen
Slide31Gamma-H2AX assay
Counting the number of DSB
Slide32Many lanthanides have good therapeutic properties
Tunable half-lifeTunable beta energyOr pure Auger cascadeOr alpha (Tb-149 is example)Same
chelation
chemistryBut- carrier free production needed for mostProduction and chemistry can be difficultMany good isotopes far from stability line
Slide33Isotopes for nuclear medicine
from ISOLDE ?Spallation by itself is dirtyHuman use requires
high
radionuclidic
purityIsotope separation needed , on- or off-lineGBq will be needed at point of useCe-134 , Nd-140 recent examplesClinical trials require year round supply – for long periods !A clinical trial should point to a commercial future
Scalability, ownership
Slide34Help from ISOLDE ?
Rapid Proof-of–principlesUltimate specific activityLabelling stability studies (recoil)Rapid extraction of radioactivity from solid targets (
example
Ga-68)
Selection of single isomer ( example Co-58m)Isotope production at ESS ?No ”ISOL”Thermal and fast neutronsPerhaps parasitic protons ,- but only 100 MeV needed.
For Science, Research and Development in Nuclear Medicine,- we can use ISOLDE
Slide3513-aug-2008Præsentationens titel
35Thank you for your attention,
….. Questions ?