Quality Control in the Hot Lab

Nuclear Medicine 2nd Edition Chapter 30

Jim Velez Director, Nuclear Pharmacy
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Agenda

Mo99/Tc99m Generator Quality Control Radiopharmaceutical QC testing:

TLC Sep Pak Misc.

Dose Calibrator QC
Accuracy Constancy Linearity Geometry

NaI detector QC FWHM value

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Quality Control
Radiopharmaceuticals and the equipment used to calibrate them require mandatory QC testing QC Federal and State Mandated

10 CFR Part 35

WAC 246-240

The primary rationale for performing QC test is patient and Nuclear Medicine personnel safety
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Mo99/Tc99m Generator Quality Control

Radionuclidic Purity

Mo-99 Breakthrough
Al3+ Breakthrough

Chemical Purity

Radiochemical Purity

Radionuclidic Purity

Mo-99 is the most common radionuclidic contaminant in an elution Tc-99 (decayed Tc-99m) is problematic Tc-99 half-life is 2.1 x 105 years virtually stable Increases patient radiation dose Decreases image quality Analyzed by gamma ray spectroscopy (MCA) or differential absorptiometry (Dose Calibrator) Performed on each generator elution The limit is 0.15 uCi Mo-99 per mCi of Tc-99m
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Chemical Purity

The presence of Alumina in the eluate (from column) Presence of Alumina:

alters normal radiopharmaceutical distribution Increases patient radiation dose Degrades image quality

Performed on each generator elution Maximum allowable alumina concentration is 10g/ml Spectrophotometric or colorimetric test
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Radiochemical Purity

Reduced hydrolyzed Pertechnetate TcO4- Pertechnetate valence is +7 USP standard is 95% Tc-99m Reduced valences +6, +5, +4 are impurities Are detected by TLC Radiochemical impurities will: cause poor kit tagging alter normal radiopharmaceutical distribution Increase patient radiation dose Degrade image quality Determined by TLC, Sep-Pak or Gel chromatography
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Mo-99 Breakthrough Test

Mo-99 breakthrough is determined using a direct assay of a generator elution via a specially designed Moly shield Moly shield design allows assay of uCi amounts of Mo-99 in the presence of Ci amounts of Tc-99m

Differential Absorptiometry

Assay elution to determine Tc-99m activity Divide total Mo-99 activity (uCi) by the total Tc99m activity (mCi) to obtain the ratio:
uCi Mo-99/mCi Tc-99m
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Aluminum Ion (Al3+) Breakthrough

Colorimetric test kit for Al3+ commercially available A drop of a standard solution containing 10 g/ml aluminum ion is placed on an indicator strip provided in the kit A drop of eluate is placed on the indicator strip next to the standard solution spot Color intensity of the two spots are compared The eluate spot color must be less intense (lighter) than the standard (the aluminum is not in excess) If more intense (darker) the eluate must be discarded Record results as positive or negative.
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Radiopharmaceutical QC
With few exceptions only Free Tc-99m and hydrolyzed reduced Tc-99m are routinely tested

Exception: Ceretec stereoisomeric dimer Usual QC methodology is TLC or Sep-Pak (MAG-3) More advanced QC can include HPLC, & GC (PET)

Common TLC Pitfalls

Inadvertently immersion of the sample spot spots are not allowed to dry when using organic solvents excessive delay in starting the TLC Table 30-5 (pg. 426) is an excellent reference of TLC criteria

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Dose Calibrator QA
Accuracy

Test designed to prove accurate reading across the devices entire energy spectrum Assessed using NIST traceable reference standard sources Several different sources are used

Usually: Co-57, Ba-133, Cs-137 and Co-60

The measured activity from the standard cannot vary more than 10% If greater or less than 10% device must be recalibrated The test is performed annually

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Dose Calibrator QA
Constancy

Test is designed to measure the ability of the dose calibrator to repeatedly measure the same specimen over time Readings are taken on ALL settings including Standard setting A long-lived standard is used Barium-133 (356 keV, Tl/2 10.7 years Cesium-137 (662 keV, Tl/2 30 years* Cobalt-57 (122 kev, T1/2 271 days The test is performed daily Observed values should be within 10% of the value for the reference standard This test performed daily
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Dose Calibrator QA
Linearity

Test designed to prove that the calibrator readout is linear over the full range from uCi to mCi activities Assessed by measuring the highest Tc-99m sample sequentially during radioactive decay Any deviation in assay value indicates equipment malfunction and nonlinearity Alternate method uses pre-calibrated lead attenuators with sequential measurements This test is performed quarterly
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Dose Calibrator QA Geometry

Assesses the calibrators ability to read the same amount of radioactivity contained in different volumes of sample Readings varying more than 10% from one volume to another, require correction factors to be calculated Factors are based on the most commonly measured volume of material determined from day-to-day clinical use (syringe, vial, etc.) This test is performed during acceptance testing of the dose calibrator, or after repair
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NaI Detector QC
Full width at half maximum (FWHM) An expression of the extent of a function, given by the difference between the two extreme values of the independent variable at which the dependent variable is equal to half of its maximum value It is an excellent indicator that the NaI , or other, detector is functioning optimally The FWHM measurement is a value only of the crystals energy-resolving ability

NOT a measurement of sensitivity

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Full width at half maximum (FWHM)

For the gamma ray spectrum of a desired isotope:

Where:
The width of the peak at half the maximum height is

divided by the photopeak energy See graph and example on pg. 431

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