Artificial WHY?? Revision What’s a radionuclide? Principle of nuclear medicine Medical Radionuclides: Naturally occurring??? Man made?? Artificial?? Artificial WHY?? 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Dr. Mohammed Alnafea alnafea@ksu.edu.sa

RADIONUCLIDE PRODUCTION 1. From stable isotopes a. Charged particle irradiation b. Neutron irradiation 2. From radionuclides (unstable) a. Spontaneous fission b. Radionuclide generator 4th lecture RAD 311 15/03/2010

Charged Particle Irradiation 4th lecture RAD 311 15/03/2010

Charged particle accelerators Cyclotron linear accelerator accelerate charged subatomic particles (p, d, ) to high energy (10 - 30 MeV) This is necessary to overcome Coulombic energy barrier to insertion into nucleus 4th lecture RAD 311 15/03/2010

1. Cyclotron 4th lecture RAD 311 15/03/2010

CTI RDS-111 Cyclotron 4th lecture RAD 311 15/03/2010

CTI RDS-111 Cyclotron Self-shielded design - no need for vault shielding for attenuation of both  and n radiation only 2 shields to move for accelerator access safety-interlocked 4th lecture RAD 311 15/03/2010

Cyclotron Targetry target material 1. internal targets Deposition vs. thin-walled target tubes 50-1000mg material in target tube; 10-50mg in solid target 1. internal targets may reach temperatures near 1000°C - water cooling required 2. external beam targets beam currents reduced due to inefficiency of beam extraction reduced product yields vs. reduced cooling requirements thermal power in target is product of beam current and projectile energy e.g. 20 MeV protons and beam current of 20µA = 4kW of power at target target backplate made of good conductor for heat dissipation copper, silver, aluminium - usually water cooled 4th lecture RAD 311 15/03/2010

CTI RDS-111 Cyclotron Targetry 4th lecture RAD 311 15/03/2010

GENERAL CHARACTERISTICS OF CYCLOTRON addition of +ve charge to nucleus leads to: tendency to decay by + or E.C. Z changes  allows separation of target and product atoms product has high specific activity )carrier free) low beam intensity of cyclotron smaller quantities of product made than in other modalities e.g. reactors expensive 4th lecture RAD 311 15/03/2010

CYCLOTRON PRODUCED RADIONUCLIDES PRODUCT DECAY MODE PRODUCTION REACTION 11C β+ 10B(d,n)11C 13N 12C(d,n)13N 15O 14N(d,n)15O 18F β+, EC 20Ne(d,α)18F 67Ga EC, γ 68Zn(p,2n)67Ga 111In 109Ag(α,2n)111In 123I 122Te(d,n)123I 201Tl 201Hg(d,2n)201Tl 15/03/2010 4th lecture RAD 311

2. Linear Accelerators 4th lecture RAD 311 15/03/2010

Linear Accelerators ION SOURCE RADIO FREQUENCY OSCILLATORS ION BEAM DRIFT TUBES TARGET acceleration occurs along linear rather than circular path rarely used for production specific applications due to high beam currents obtainable 89Sr, 125I + other brachytherapy sources 4th lecture RAD 311 15/03/2010

Educational Video 4th lecture RAD 311 15/03/2010

1.b Neutron irradiation 4th lecture RAD 311 15/03/2010

Nuclear Reactor 4th lecture RAD 311 15/03/2010

Nuclear Reactors two production processes - neutron bombardment fission reactors serve as a source of neutrons produced as a result of nuclear fission reactors serve as a source of fission fragments 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Neutron bombardment resistance to insertion of neutron into nucleus less than for proton neutron capture by stable nucleus - (n,) reaction produces neutron rich radionuclides 4th lecture RAD 311 15/03/2010

NUCLEAR REACTOR Schematic Representation 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Thermal neutron induced fission 235U is most commonly used fissionable material 235U + n  unstable nucleus  fission fragments + n + E average number of neutrons per fission = 2.4 self-irradiation of 235U - self sustaining chain reaction moderators included to slow neutrons to thermal energies - deuterium oxide, graphite 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Thermal neutron induced fission 235U fission  > 370 nuclides observed mass range : 72 - 161 distribution as indicated 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Thermal neutron induced fission radionuclides extracted when fuel elements replaced chemical separation techniques used precipitation, solvent extraction, chromatography products usually (carrier free), high specific activity fission produced radionuclides usually neutron rich decay by - emission relatively cheap - not major function of reactor 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Reactor Targetry irradiation positions mobile : short irradiation times (minutes - 1 week) fixed : long irradiation times (one or more reactor fuel cycles : 2 - 4 weeks) accessible only during reactor shutdown both positions water cooled reactor temperature  100°C, sample temperature > 1000°C ( heating) target design pure element often best choice – high melting point and density prevention of target rupture primary safety consideration use of mercury and cadmium prohibited reactivity of mercury with aluminium (fuel cans) high neutron absorption of cadmium (reactor operation) 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Neutron bombardment Activity of a radionuclide produced by particle bombardment is given by A = N (1 - e-t) where: A = activity  = particle flux (number/cm2/s) N = number of target atoms  = absorption cross section in barns (10-24 cm2/atom)  = decay constant of product radionuclide t = duration of irradiation (in seconds) when t > 4 x T½ , (1 - e-t) approaches 1 saturation activity : A = N no gain from irradiating beyond 3 - 4 x T½ 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Preparation of I-131 (carrier) Starting material : 2.5g 93+% 235U flux: 2 x 1014n/cm2/sec, 28d target stored for 7d following irradiation dissolved in 4.5M NaOH + heating 133Xe released - trapped (charcoal, liquid N2) Al2O3.2H2O + NaI + H2SO4 + H2O2 - distilled  7500 GBq 131I (+ 127I + 124I) i.e. carrier iodine 235U recovered for reuse 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Preparation of I-131 (carrier free) target : 2.5g 99+% 130Te Neutron flux: 2 x 1014n/cm2/sec, 21d 130Te (n,) 131Te  131I  65 GBq 131I obtained by distillation, as before 130Te recovered for reuse 4th lecture RAD 311 15/03/2010

RADIONUCLIDE PRODUCTION Preparation of Mo-99 (non-fission + fission) target : natural MoO3 - 23.78% 98Mo flux: 2 x 1014n/cm2/sec, 7d 98Mo (n,) 99Mo  37 GBq 99Mo from 1g MoO3 natural MoO3  185W (T½ = 74d) - absent when enriched 98Mo used Starting material : 2.5g 93+% 235U 99Mo extracted from acidified solution of fission products produced in 1000 GBq quantities high specific activity for generators may contain some 131I and 103Ru 4th lecture RAD 311 15/03/2010

REACTOR PRODUCED RADIONUCLIDES PRODUCT DECAY MODE PRODUCTION REACTION 14C β- 14N(n,p)14C 32P 31P(n,γ)32P 51Cr EC, γ 50Cr(n,γ)51Cr 59Fe β-, γ 58Fe(n,γ)59Fe 125I 124Xe(n,γ)125Xe EC 125I 131I 130Te(n,γ)131Te β- 131I 15/03/2010 4th lecture RAD 311

Do we have to have a cyclotron or an accelerator in each hospital ???????

Generator TC99m- Generator 15/03/2010 4th lecture RAD 311

2 Compounds Parent Daughter Long half life Short half life Equilibrium

RADIONUCLIDE PRODUCTION Radionuclide Generators allows distribution of short lived nuclides to centres remote from production site long(er) lived parent nuclide decays to daughter nuclide allows separation of daughter from parent separation achieved by difference in chemical properties e.g. charge - ion exchange chromatography 4th lecture RAD 311 15/03/2010

RADIONUCLIDE GENERATORS Cross-section of a typical radionuclide generator 4th lecture RAD 311 15/03/2010

RADIONUCLIDE GENERATORS Radioactive Decay Laws common simplifications T½ parent  10 x T½ daughter transient equilibrium e.g. 99Mo / 99Tcm generator 66h 6.02h 4th lecture RAD 311 15/03/2010

RADIONUCLIDE GENERATORS Radioactive Decay Laws common simplifications T½ parent >> T½ daughter (p >> d) secular equilibrium e.g. 68Ge / 68Ga generator 270d 68m 4th lecture RAD 311 15/03/2010

RADIONUCLIDE GENERATORS Desirable Properties ease of operation daughter should have high chemical and radionuclidic purity daughter should be a different chemical element to parent should remain sterile and pyrogen free daughter should be in a form suitable for preparation of radiopharmaceuticals 4th lecture RAD 311 15/03/2010

Technetium Generator Elution WARNING - PLEASE NOTE: If using a laptop and projector to display this presentation, the movie MAY not project correctly. It will, however, run OK on the laptop. This problem may be overcome, somewhat inelegantly, by temporarily disabling the display on the laptop display. If this is done (using the keystroke combination applicable for your particular laptop) the movie will then project OK. Simply toggle through the keystroke to display the presentation on both the laptop display and the projector when moving onto the next slide. The movie is not quite shown in real time. There is about a 1 minute segment removed from the middle of the movie, when the saline is filling the elution vial – rather boring to watch once you’ve grasped what is happening. The entire elution process takes about 3 or 4 minutes in reality. This would normally be done behind thick lead shielding, often in a sterile glove box. However, for the sake of clarity, this elution of an expired generator has been done on a laboratory bench. 15/03/2010 4th lecture RAD 311

RADIONUCLIDE GENERATORS Yield Problems yield is always < 100% caused by reduced access of eluant to support bed due to - poor quality ion exchange material channelling in column during transportation improper initial packing of column terminal sterilisation procedures pseudochannelling - dry vs. wet generators 4th lecture RAD 311 15/03/2010

Commonly Used Radionuclides Characteristics Production Method Decay Mode  Emissions (keV) Half-life IMAGING 18F Cyclotron Positron 511 108 min 67Ga EC 92, 182, 300, 390 78 hr 81Krm Generator IT 191 13 s 99Tcm 140 6 hr 111In 173, 247 67 hr 123I 160 13 hr 131I Reactor Beta 280, 360, 640 8 d 201Tl 68-80 73.5 hr THERAPY 90Y - 64 hr 186Re 137 90 hr In Vitro 14C 5760 yr 51Cr 323 27.8 d 125I 27-35 60d 4th lecture RAD 311 15/03/2010

Educational Video

Assignment A Mo99m/Tc99m Generator is in transient equilibrium. If the radioactivity of Mo99m at that time is 16 GBq, how much radioactivity of Tc99m will be available 134 hours later if no milking took place during this interval? Mo99m T1/2= 67 hrs Tc99m T1/2= 6 hours 4th lecture RAD 311 15/03/2010

Thank you hnalahamad@ksu.edu.sa 4th lecture RAD 311 15/03/2010