8.2 Radiochemical Purity & Dose Calibrator Quality Control

Radiochemical Purity & Dose Calibrator QC

Ensuring that the correct dose of the correct pharmaceutical is administered to the patient is the most fundamental responsibility in the nuclear pharmacy. This is achieved through rigorous Quality Control (QC) of both the radiopharmaceutical itself (Radiochemical Purity) and the equipment used to measure it (Dose Calibrator QC).

Radiochemical Purity

Radiochemical Purity is defined as the proportion of the total radioactivity in the sample that is present in the desired chemical form. For example, in a vial of Tc-99m MDP, we want to know what percentage of the Tc-99m is actually bound to the MDP ligand. The United States Pharmacopeia (USP) sets strict limits; for most Tc-99m radiopharmaceuticals, the purity must be greater than 90% or 95% before it can be administered to a patient.

Types of Impurities

In Tc-99m radiopharmaceutical preparations, there are three possible chemical forms of technetium:

1. Bound Tc-99m: This is the desired product (e.g., Tc-99m bound to MDP).
2. Free Pertechnetate (NaTcO4): This is the unreduced Tc-99m (Tc7+) that failed to bind to the ligand. It localizes in the thyroid gland, salivary glands, and stomach. High levels of free pertechnetate severely degrade image quality, especially in bone scans.
3. Hydrolyzed-Reduced Tc-99m (HR-Tc): This is Tc-99m that was reduced by the stannous ion but reacted with water instead of the ligand, forming an insoluble colloid (TcO2). This impurity gets phagocytized by the reticuloendothelial system, improperly localizing in the liver and spleen.

Thin Layer Chromatography (TLC / ITLC)

The standard method for separating and quantifying these components is Instant Thin Layer Chromatography on Silica Gel paper (ITLC-SG). Chromatography separates chemical compounds based on their differential affinities for a stationary phase (the paper strip) and a mobile phase (the solvent).

The Process:

1. A tiny drop of the radiopharmaceutical is placed at the bottom (origin) of an ITLC strip.
2. The strip is placed in a small vial containing a specific solvent (mobile phase).
3. The solvent creeps up the paper via capillary action, dragging certain chemical forms with it to the solvent front, while leaving others at the origin.
4. The strip is cut in half, and the radioactivity of the top half and bottom half is counted in a well counter or dose calibrator.

Common Solvent Systems: Testing often requires a two-strip system because no single solvent separates all three forms.

• Solvent 1 (e.g., Acetone or MEK): In acetone, Free Pertechnetate moves to the top (solvent front), while Bound Tc-99m and HR-Tc stay at the bottom (origin). This isolates the percentage of Free Pertechnetate.
• Solvent 2 (e.g., Saline or Distilled Water): In saline, Bound Tc-99m and Free Pertechnetate move to the top, while the heavy, insoluble HR-Tc stays at the bottom (origin). This isolates the percentage of HR-Tc.

Calculating % Purity

To calculate purity, you first calculate the percentage of each impurity, then subtract them from 100%.

% Free Pertechnetate: = (Counts at Top in Acetone) / (Total Counts on Acetone Strip) x 100 % HR-Tc: = (Counts at Bottom in Saline) / (Total Counts on Saline Strip) x 100

% Radiochemical Purity = 100% - (% Free Pertechnetate + % HR-Tc)

If the purity is 96%, the preparation passes and can be dispensed. If it is 85%, the entire vial must be discarded.

Dose Calibrator Quality Control

The dose calibrator is an ionization chamber used to measure the activity of radionuclides before administration. Regulatory agencies mandate four specific QC tests to ensure the dose calibrator is functioning correctly across different isotopes, activities, and volumes. These are remembered by the acronym CLAG.

1. Constancy (Daily)

• Frequency: Daily, before the calibrator is used.
• Purpose: To verify that the dose calibrator's reading is consistent day after day.
• Procedure: A long-lived reference source, typically Cesium-137 (Cs-137) or Cobalt-57 (Co-57), is measured on multiple isotope settings (e.g., Tc-99m, I-131, Tl-201). The measured activity is compared to the expected decayed activity for that day.
• Tolerance: Readings must be within +/- 10% of the expected value. If it fails, the unit cannot be used.

2. Linearity (Quarterly)

• Frequency: Quarterly (every 3 months).
• Purpose: To prove the calibrator can accurately measure activity across a wide range, from the highest dose administered (e.g., 200 mCi) down to very small amounts (e.g., 10 or 30 uCi).
• Procedure: A high-activity source of Tc-99m is measured. It is then repeatedly measured over several days as it decays (decay method), or measured using calibrated lead shields of varying thickness to simulate decay (sleeve/shield method, like Calicheck).
• Tolerance: Readings must be within +/- 10% of the calculated expected decay values across the entire range.

3. Accuracy (Annually)

• Frequency: Annually (at least once a year) and at installation.
• Purpose: To ensure the calibrator is providing a truly accurate reading, traceable to national standards.
• Procedure: Measurements are taken using at least two different certified reference sources with known, calibrated activities and different photon energies (e.g., Cs-137 for high energy, Co-57 for low energy).
• Tolerance: Readings must be within +/- 5% of the certified calibrated activity (after correcting for decay).

4. Geometry (At Installation / Repair)

• Frequency: At installation, and if the instrument is moved or repaired.
• Purpose: To verify that the calibrator reads the same activity regardless of the volume of liquid or the type of container (syringe vs. vial).
• Procedure: A small volume (e.g., 1 mL) of activity is measured in a vial. Saline is progressively added to increase the volume (to 2 mL, 4 mL, 8 mL, etc.), and the vial is measured at each step. The same procedure is done with syringes of different sizes.
• Tolerance: All readings must remain within +/- 10% of the initial reading. Correction factors must be calculated if variations exceed this limit.

Strict documentation of all these tests is required by the NRC and agreement states, as errors in the dose calibrator result in direct radiation misadministrations to patients.