Medical Radionuclide Production

Common Radionuclides In Medicine

Brachytherapy Sources

Nuclide	Half-life	Photon Energy (MeV)	HVL (mm Lead)	Exposure Rate Constant (R-cm²/mCi-hr)
¹⁹²Ir	73.8 days	0.38 average	2.5	4.69
²²⁶Ra	1,600 years	0.83 average	12.0	8.25
²²²Rn	3.83 days	0.83 average	12.0	10.15
⁶⁰Co	5.26 years	1.17, 1.33	11.0	13.07
¹³⁷Cs	30.0 years	0.662	5.5	3.26
¹⁹⁸Au	2.7 days	0.412	2.5	2.38
¹²⁵I	59.4 days	0.028 average	0.025	1.46
¹⁰³Pd	17.0 days	0.021 average	0.008	1.48

PET Nuclides

Nuclide	Half-life (minutes)	Positron Maximum Energy (MeV)	Dose rate constant (μSv m²/MBq)
¹⁸F	109.8	0.63	0.143
¹¹C	20.4	0.96	0.148
¹³N	10.0	1.19	0.148
¹⁵O	2.0	1.72	0.148
⁶⁴Cu	762	0.65	0.029
⁶⁸Ga	68.3	1.9	0.134
⁸²Rb	1.27	3.35	0.159
¹²⁴I	6048	1.54, 2.17	0.185

Data taken from AAPM TG-108

A Closer Look At Medical Nuclides

Iridium-192

Ir-192

Iridium-192 (¹⁹²Ir) is the most common isotope used in high dose rate (HDR) brachytherapy. It is a man-made isotope produced by neutron bombardment of Iridium-191. (¹⁹²Ir) decays primarily through β^- decay to an excited state of Platinum-192 which is stable. Approximately 5% of decays occur via electron capture yielding an excited state of Osmium-192 which is also stable. It is regarded as superior to cobalt-60 and cesium-137 due to its higher specific activity which allows for smaller source sizes. One disadvantage to (¹⁹²Ir) is its short half life (73.83 days) which results in a loss of activity of approximately 1% per day. This necessitates source changes every 3-4 months.

Half-life: 73.83 days
Activity loss per day (quick estimate): 1%/day
Decay modes
- 95.6% β^- decay to excited state of ¹⁹²Pt
- 4.4% Electron capture to excited states of ¹⁹²Os
Exposure rate constant
Air kerma rate constant
Photon energy
- 0.136-1.06 (0.38 average) MeV
Half-value layer (mm lead): 2.5mm

IR-192 decay scheme

Cesium-137

Encapsulated Cs-137 check source

Cesium-137 (¹³⁷Cs) is a radioisotope that has been used in both interstitial and intracavitary brachytherapy. Although Cs-137 decays via beta-decay, it is the daughter nuclide's subsequent gamma emissions that are responsible for most dose when used as an enclosed source in cancer treatment. Elemental Cesium has a low melting point (28.5°C, 83.3°F) and so is most commonly supplied in the form of insoluble powders or ceramic microspheres doubly encapsulated in stainless steel tubes or needles.

Half life: 30.07 years
- Activity loss per year: ~2%
- Clinical Source Life: ~7 years
Decay mode: β^-
γ Energy: 0.662MeV
Exposure rate constant
Lead HVL: 5.5mm

Cobalt-60

Cobalt 60

Cobalt-60 (⁶⁰Co) is a synthetic radioisotope that has been used in both external beam radiation therapy and brachytherapy. ⁶⁰Co decays via β^- decay to an excited state of Nickel-60 which then emits two high energy (1.17MeV and 1.33MeV) gamma rays. It is these energetic gamma rays which are primarily important for use in radiation therapy. The β particle emitted is absorbed by the cobalt metal and the source's encapsulation such that it doesn't contribute meaningfully to the dose distribution. Cobalt-60 has been largely replaced by Iridium-192 in high dose rate brachytherapy and by linear accelerators in external beam radiation therapy. Because of its high activity and simple gamma spectrum, it is used in the calibration of radiation detectors. Today it is also used in some MRI-guided external beam therapy systems because Cobalt-60 is able to generate an MV beam without strongly influencing a magnetic field.

Half-life: 5.2714 years
Decay mode: β^-
Mean gamma energy: 1.25MeV (1.17MeV and 1.33MeV)
- ~10% of the beam is resultant of scattered photons.
Lead HVL: 11.0mm
Exposure rate constant
External beam source size: 1-2cm²
- This increases beam penumbra.

Cobalt-60 decay scheme

Use in Brachytherapy

Cobalt-60 was used in brachytherapy in the past but is rarely used today. Compared with Iridium-192, Cobalt-60 is more expensive and requires a larger source size for the same dose rate but has the advantage of a longer half-life. The dose distribution is more dominated by inverse square law than Iridium-192, leading to a slightly shallower dose fall-off.

Co-60 vs Ir-192 radial dose distribution.

Use in External Beam Therapy

Cobalt-60 is the radionuclide of choice for nuclide-based external beam radiation therapy. Compared to other radionuclides used for this purpose (Radium-226 and Cesium-137), ⁶⁰Co has a greater specific activity and a higher energy. Greater specific activity allows for smaller source size and higher energy allows for a more penetrating and more skin sparing field. Cobalt-60 external beam therapy has recently been incorporated in online MR guided radiation therapy programs where it's ability to generate an MV beam without significantly perturbing the MRI's magnetic field is a great advantage.

Iodine-125

Iodine-125 (¹²⁵I) is used primarily as a low dose rate (LDR) brachytherapy source. It's half-life (59.4 days) and low photon energy (28keV) allows for medium term storage with minimal shielding. ¹²⁵I decays solely via electron capture to an excited state of tellurium-125 (¹²⁵Te). This excited state of ¹²⁵Te is not a metastable state and it decays to a ground state via internal conversion or gamma emission. Because of the low energy and the presence of end welds on the source's encapsulation, ¹²⁵I seeds are often highly anisotropic. Significant differences exist in the published exposure rate constant and mean photon energy of Iodine-125 which are largely the result of differences in handling the low energy photon spectrum.

Half-life
- 59.4 days
Decay modes
- Electron Capture to first excited state of ¹²⁵Te (100%)
- ¹²⁵Te decays to ground state of ¹²⁵Te via
  - Internal conversion (93%)
    - Characteristic x-ray energies of 27 to 35keV
  - γ-emission (7%)
    - 35.5keV
Exposure rate constant
Air kerma rate constant
Average photon energy
- 28 keV
Average photons per decay
- 1.4
Half-value layer (mm lead)
- 0.008

Palladium-103

Radium-226

Radium-226 decay scheme

Discovered in 1898, Radium-226 (²²⁶Ra) was the first common radionuclide used in brachytherapy. With a half-life of 1600 years, Radium-226 is the most stable form of Radium. Radium undergoes alpha decay to Radon-226. The decay chain of Radium-226 ends in stable lead (Pb-206). Approximately 49 gamma rays with energies ranging from 0.184 to 2.45 MeV are released during the decay from Radium to Lead.

Because Radium-226 has a significantly longer half life than its daughter products, it will exist in secular equilibrium with its daughter products. The time to reach equilibrium for a new source is approximately 1 month. Finally, the decay process of Radium-226 results in a build-up of Radon gas. This can be an important consideration in the design of an encapsulated Radium brachytherapy needle.

Half-life: 1,600 years
Decay mode: Alpha, Beta
Average photon energy: 0.83 MeV (approximately 49 photons released per decay with an energy range of 0.047 - 2.45 MeV)
Exposure rate constant:

Ytterbium-169

Sample or Ytterbium-169

Ytterbium-169 (¹⁶⁹Yb) was explored as a potential radioisotope for LDR and HDR applications due to its low average energy (93keV). The lower energy allows for reduced shielding and opens the potential for small directionally shielded sources or applicators.

Half-life: 32.03 days
Average energy: 93keV (Excluding <10keV photons)
Exposure rate constant
Air kerma rate constant
Roentgen-to-rad conversion factors (f_med)
Lead attenuation
- First HVL = 0.2mm
- First TVL = 1.6mm
Decay Mode: Electron Capture

Ytterbium-169 decay scheme

Yttrium-90

Yttrium-90 (⁹⁰Y) is a beta (electron) emitter with an average energy of 0.9267 MeV and a half-life of 2.67 days. Over 90% of emitted energy is absorbed within 5.3mm and the maximum range of emitted electons is 11mm. Y-90 is most commonly used in radiation therapy as the source in microsphere liver treatments.

Half life: 2.67 days
- Decays approximately 1% per hour
Decay mode: β^–
Beta energy: 0.9267 MeV (mean)

Y-90 Decay Scheme

Methods of Radionuclide Production

Radionuclides used in nuclear medicine have a short half-life which allows for faster treatments, faster imaging, and lower public exposure. As a result of the need for such short half-lives, most radiopharmaceuticals in use today must use artificially generated radionuclides. The vast majority of these nuclides are produced in cyclotrons, nuclear reactors, and radionuclide generators.

Nuclear Transformation Notation

Nuclear transformations are denoted T(P, E)R where T is the target material, P is the accelerated particle type, E is the number and type of emitted particles during transformation, and R is the resulting radionuclide.

For example, the notation for Gallium-67 production is ⁶⁸Zn (p, 2n) ⁶⁷Ga which indicates that a proton (p) was accelerated into ⁶⁸Zn which produced ⁶⁷Ga by the emission of two neutrons (2n).

Often, the desired radionuclide is produced after decay of a bombardment produced radionuclide.

For example, Iodine-123 is produced via the (p, 5n) transformation to Xe-123 which then undergoes electron capture (EC) to yield I-123.

Nuclear fission resultant of neutron absorption is indicated as in the below example. The creation of Mo-99 (a parent of Tc-99m) via thermal neutron bombardment and subsequent decay of U-235. Note that in addition to Mo-99 and Sn-134, three neutrons and additional gamma photons are produced with a net energy release of about 200 MeV.

Cyclotrons

A cyclotron is a charged particle accelerator consisting of an evacuated cylinder divided into two sections referred to as "Dees" (because they look like a capital D).The evacuated cylinder is placed between two large magnets producing a constant magnetic field. Charged particles are injected into the center of the cylinder and an oscillating electric field is applied to the Dees. The electric field causes the charged particles to accelerate and the constant magnetic field causes that acceleration to have a circular trajectory. The energy and velocity of the particles increase as they pass from one Dee to the other.

Radionuclides are produced by colliding these high energy-charged particles into target nuclei. The accelerated particle type, its energy, and the target material all impact what nuclides will be produced. Cyclotron-produced nuclei will be created in an excited state and will decay either by particle (protons and neutrons) or electromagnetic (photon) emissions. Most cyclotron-produced radionuclides are neutron deficient and decay via either electron capture (EC) or positron emission (β⁺).

Key Point: Most Positron Emission Tomography (PET) radionuclides are produced in cyclotrons.

Cyclotron accelerator used to create radionuclides and radiopharmaceuticals.

Nuclear Reactors

Nuclear reactors are commonly used to produce radionuclides via nuclear fission or nuclear activation.

Nuclear Fission

Nuclear fission is the splitting of a heavy atom into multiple smaller nuclei. Nuclear fission is induced in a nuclear reactor by the absorption of thermal (low energy) neutrons. Medical radionuclides may be produced as a decay product of these nuclear fusions.

Nuclear Activation

Neutrons produced in a nuclear reactor may also be used to bombard stable nuclei in a process known as nuclear activation. When the stable nucleus absorbs a neutron, it produces an isotope with a moderate half-life.

The most common neutron activation methods are the (n, γ) reaction, in which neutron capture is immediately followed by emission of a gamma photon, and the (n, p) or (n, α) reactions in which a proton or alpha particle is emitted immediately after neutron absorption.

Radionuclide Generators

Radionuclide generators produce a short-lived medical radionuclide by decay of a longer-lived radionuclide. The most common example of a clinically useful radionuclide generator is the Molybdenum-99/Technitium-99m generator often referred to as Moly Cows.

Moly Cows (Tc-99m Generators)

In a Moly Generator, a sample of Mo-99 (in the form of ammonium molybdenate) is loaded into a porous column containing aluminum oxide resin. The ammonium molybdenite becomes attached to the surface of the resin, greatly increasing its surface area. When the Mo-99 decays to Tc-99m, the Tc-99m is less tightly bound to the resin than its parent, Mo-99. This allows the Tc-99m to be washed from the resin and collected while leaving the Mo-99 behind. This washing process is referred to as “milking” and gives rise to the name Moly Cow (i.e. “milking the cow”).