A Tutorial by Stephen M. Karesh, PhD

Adapted for the Web by Stephen M. Karesh, PhD & Marsha Lipps CNMT



a. Types of equilibriu
Secular equilibrium: a condition reached when the tphys of the parent is many times greater than the tphys of the daughter, e.g., 100-1000 times greater. To keep things in perspective, during 10 half-lives of the daughter, decay of the parent is negligible. Decay of the parent is represented by the flat line in the diagram below.

Transient equilibrium : a condition reached when the tphys of the parent is approximately 10 times greater than the
tphys of the daughter. A classical example is the Mo-99/Tc-99m Generator. During the 67 hr period representing 11 half-lives of Tc-99m, 50% of the Mo-99 has disappeared, as noted in the following diagram. In both transient and secular equilibrium, apparent half-life of the daughter = physical half-life of the parent

b. Characteristics of ideal generator system
A generator is a self-contained system housing a parent/daughter mixture in equilibrium, which is designed to yield the daughter for some purpose usually separate from the parent. The principal utility is to produce certain radioisotopes on-site which, because of their short half-lives, cannot be shipped by commercial sources. To be useful, the parent's half-life must be long compared to the travel time required to transport the generator to the recipient.

1. If intended for clinical use, the output of the generator must be sterile and pyrogen-free.
2. The chemical properties of the daughter must be different than those of the parent to permit separation of daughter from parent. Most often, separations are performed chromatographically.
3. Generator should be eluted with 0.9% saline solution and should involve no violent chemical reactions. Human
intervention should be minimal to minimize radiation dose.
4. Daughter isotope should be short-lived gamma-emitting nuclide (physical half-life = hrs-days)
5. Physical half-life of parent should be short enough so daughter regrowth after elution is rapid, but long enough
for practicality.
6. Daughter chemistry should be suitable for preparation of a wide variety of compounds, especially those in kit form.
7. Very long-lived or stable granddaughter so no radiation dose is conferred to patient by decay of subsequent

8. Inexpensive, effective shielding of generator, minimizing radiation dose to those using it.
9. Easily recharged (we do NOT recharge Mo/Tc generators, but store them in decay areas after their useful life
is over).

Clinically useful, commercially available radionuclide generators are listed below: All of these generators are
examples of secular equilibrium, except for the Mo/Tc generator, which is transient equilibrium.

Answer: elution profile of a generator for first five days of the week. Slope of the line represents the decay rate of
the parent nuclide.

c. Principles of operation of a Mo/Tc generator
1. Prior to shipping the generator to the Nuclear Medicine Department, Mo-99 sodium molybdate is immobilized on a column of alumina (Al2O3; aluminum oxide) due to its very high affinity for alumina.

2. 0.9% saline solution (the eluant) is passed through the column and sodium pertechnetate, the daughter of Mo-99 decay, is eluted from the column due to its almost total lack of affinity for alumina.
3. The pertechnetate is collected in a shielded, evacuated sterile vial and calibrated prior to use. It is referred to as the eluate.

4. Quantitative removal of pertechnetate is attributed to the lack of affinity of pertechnetate for alumina, whereas molybdate is essentially completely and irreversibly bound to the alumina.
5. When eluting the generator, the elution volume should be carefully controlled so a relatively constant radioconcentration is obtained every day.

d. Quality control of Mo/Tc generator

Radionuclidic impurity is Mo-99; results in Increased Radiation Dose, poor image quality
Radiochemical HRTc-reults in Poor Image Quality; Increased Radiation Dose
Chemical impurity- Al
3+ results in Poor Image Quality due to labeling problems

Mo Breakthrough, Every Elution- specification: <0.15 μCi Mo/mCi Tc at time of injection
3+ Ion Breakthrough, Every Elution- specification: <10 ppm of Al3+; may be expressed as μg/ml

Hydrolyzed Reduced Tc- Every Elution, specification: < 2% (Reasonable Limit, presently no legal limit)

1. Mo-99 Breakthrough: Mo-99 is assayed directly in the special lead pig supplied by the manufacturer of your dose calibrator. Tc-99m is then assayed directly in the plastic sleeve in your dose calibrator. Activity (uCi) of Mo-99is divided by activity (mCi) of Tc-99m to obtain a ratio. If this ratio is <0.15 μCi Mo-99 per mCi of Tc-99m at time of injection, the generator
eluate has passed the Mo-99 Breakthrough Test. As a rule of thumb, if the ratio is <0.038 at time of elution, the material will be suitable for injection for at least 12 hours.
2. Aluminum Ion Breakthrough: Al3+ ion is measured colorimetrically. A drop of the eluate is placed on one end of a special test paper; a drop of a standard solution of Al
3+, concentration 10 ppm, is placed on the other end of the test strip. If the color at the center of the drop of eluate is less red than that of the standard solution, the eluate has passed the Aluminum Ion Breakthrough Test. Units may be expressed as ug/ml.






April 5, 2010