Mo-99/Tc-99m Generator
The Molybdenum-99/Technetium-99m generator is the “workhorse” of nuclear medicine, providing an on-site source of Tc-99m.
Learning Objectives
- Explain the parent-daughter relationship and transient equilibrium
- Describe the construction and operation of the generator
- Calculate elution efficiency and theoretic yield
- Understand Mo-99 and Alumina breakthrough limits
Principle
The generator relies on Transient Equilibrium, where the parent (Mo-99) half-life is longer than but not significantly greater than the daughter (Tc-99m).
- Parent: Molybdenum-99
- Half-life: 66 hours
- Source: Fission of U-235 (reactor produced)
- Chemically mimics: Sulfate (MoO₄²⁻)
- Daughter: Technetium-99m
- Half-life: 6 hours
- Chemically mimics: Pertechnetate (TcO₄⁻)
Generator Construction
- Column: Contains Alumina (Al₂O₃)
- Loading: Mo-99 (as Molybdate) is adsorbed onto the alumina column.
- Elution: Saline (0.9% NaCl) is passed through the column.
- Mo-99 binds tightly to alumina.
- Tc-99m (as pertechnetate) binds loosely and washes off with saline.
Elution Profile
- Typical elution efficiency is 75-85%.
- Maximum Tc-99m yield occurs roughly every 23-24 hours.
Quality Control (The “Moly Breakthrough” Test)
We must ensure that the eluate contains pure Tc-99m without contaminants from the column.
1. Radionuclidic Purity (Moly Breakthrough)
- Limit: < 0.15 µCi Mo-99 per 1 mCi Tc-99m (at time of administration).
- Test: Comparison shield method (Moly Assay Canister).
- Place eluate in lead shield (blocks 140 keV Tc gammas, allows high energy Mo-99 gammas ~740/780 keV to pass).
- Measure unshielded (total activity) and shielded (Mo-99 only).
2. Chemical Purity (Aluminum Breakthrough)
- Contaminant: Aluminum ion (Al³⁺) from the column.
- Limit: < 10 µg Al³⁺ per mL.
- Test: Colorimetric spot test (Aurintricarboxylic acid).
- Compare color of drop to standard solution. Pink/red indicates excess aluminum.
- Consequence: Excess Al³⁺ causes Tc-99m colloid formation → liver/lung uptake.
| Impurity | Type | Limit | Test |
|---|---|---|---|
| Mo-99 | Radionuclidic | < 0.15 µCi/mCi | Dose Calibrator with Shield |
| Al³⁺ | Chemical | < 10 µg/mL | Colorimetric Paper |
| Pyrogens | Biological | USP limits | LAL Test (Manufacturer) |
Transient Equilibrium: Occurs when T½ parent > T½ daughter (e.g., 66h vs 6h). Activities run parallel.
Secular Equilibrium: Occurs when T½ parent » T½ daughter (e.g., Ra-226 1600y vs Rn-222 3.8d). Activities become equal.