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

  1. Column: Contains Alumina (Al₂O₃)
  2. Loading: Mo-99 (as Molybdate) is adsorbed onto the alumina column.
  3. 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.
ImpurityTypeLimitTest
Mo-99Radionuclidic< 0.15 µCi/mCiDose Calibrator with Shield
Al³⁺Chemical< 10 µg/mLColorimetric Paper
PyrogensBiologicalUSP limitsLAL 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.