In the intricate world of nuclear medicine, a tiny impurity can make the difference between a clear diagnosis and a misleading image.
When you hear the term "medical imaging," you might think of X-rays or MRIs. But behind the scenes, a more dynamic process is at work. Every day, in hospitals worldwide, pharmacists prepare special compounds called radiopharmaceuticals—drugs carrying a tiny amount of radioactive material that helps doctors see inside our bodies. The most common workhorse is Technetium-99m (99mTc), used in millions of procedures each year to diagnose conditions from heart disease to cancer. But these drugs have a shelf life of mere hours. Before administration, a critical question must be answered: is the product pure enough to be both safe and effective? This is the crucial role of radiochemical purity testing.
Radiochemical purity (RCP) is defined as the proportion of the total radioactivity present in the desired chemical form. In simpler terms, it answers the question: "Is all the radiation coming from the drug we intended to make, or are there unwanted radioactive impurities?"
The primary impurity, free pertechnetate ([99mTc]TcO4−), behaves like iodide in the body and is taken up by the thyroid, stomach, and salivary glands. This can lead to unwanted radiation exposure to these organs 2 .
Impurities can compromise image quality, potentially obscuring the area of clinical interest and leading to misdiagnosis 2 .
International pharmacopoeias and manufacturers set strict RCP limits, usually ≥90% to ≥95%, depending on the specific radiopharmaceutical. But performing these tests takes time, resources, and specialized staff. In a field where every minute counts, finding the optimal balance between rigorous testing and practical efficiency is a constant challenge for nuclear medicine departments.
To understand the real-world need for purity testing, a research team conducted a comprehensive study at a single institution over three years. They tracked and analyzed 2,280 separate preparations of eight different 99mTc-radiopharmaceuticals, all prepared by four experienced technologists following strict, ISO9001-certified procedures 1 .
Separate Preparations
Study Duration
Radiopharmaceuticals
Every preparation and quality control test was performed according to the manufacturer's Summary of Product Characteristics (SPC) 1 .
The study included a wide range of common agents, such as 99mTc-tetrofosmin (for heart imaging), 99mTc-oxidronate (for bone scans), and 99mTc-albumin colloid (for lymph node mapping) 1 .
Volumes were measured with validated precision pipettes, and radioactivity was counted using a standardized "cut and count" technique with a dose calibrator to ensure accuracy 1 .
All quality controls were performed before administering the radiopharmaceutical to the patient, acting as a final safety gate 1 .
After three years and thousands of tests, the results were telling. Out of 2,280 preparations, only six (0.26%) failed to meet the RCP limits required for clinical use 1 .
A deeper dive into these six failures was even more instructive. Five were due to gross technical errors in measurements and manual procedures. Because testing was done pre-administration, these batches were immediately identified and repeated, successfully producing pure products. The sixth failure was attributed to an incubation time that, while compliant with the manufacturer's instructions, was still insufficient 1 .
This study powerfully demonstrates that in a well-controlled system, the failure rate is exceptionally low. The vast majority of impurities arise not from the kits themselves, but from human error in the preparation process.
| Radiopharmaceutical | Use Case | Minimum RCP Limit |
|---|---|---|
| 99mTc-Tetrofosmin | Myocardial Perfusion Imaging | ≥ 90% |
| 99mTc-Oxidronate (HDP) | Bone Scintigraphy | ≥ 95% |
| 99mTc-Albumin Colloid | Lymphoscintigraphy | ≥ 95% |
| 99mTc-Exametazime | Cerebral Blood Flow | ≥ 80% |
So, how is this vital purity check actually performed? The toolkit for testing radiochemical purity is specialized but straightforward.
The workhorse method. A strip of paper or glass coated with silica gel is used to separate different chemical species based on how far they travel with a solvent 2 6 .
Example: A drop of the 99mTc-radiopharmaceutical is spotted on the strip, which is placed in a jar with a small amount of solvent. The solvent moves up the strip, carrying impurities at different speeds.
The surface on which the separation occurs. Different materials separate impurities differently.
Example: iTLC-SG (silica gel) and iTLC-SA (silica gel with an inorganic binder) are common types. The choice depends on the radiopharmaceutical being tested 2 .
An alternative to TLC. The sample is passed through a cartridge that traps some components while letting others pass through 6 .
Example: Used for 99mTc-MAG3 (a kidney agent). The cartridge is pre-treated, and the radiopharmaceutical is added. Different solutions are passed through to elute impurities and the pure product into separate vials.
Measures the radioactivity in the separated components to calculate the purity percentage.
Example: This can be a dedicated dose calibrator (activimeter) or, as recent research shows, even a properly calibrated Geiger-Müller counter, offering a robust and portable alternative 5 .
The evidence suggests that "how much is enough" is not a one-size-fits-all answer. The three-year study concluded that the quality of the final product hinges on a controlled production system built on specific standard operating procedures and strict adherence to guidelines 1 . In such a controlled environment, the failure rate is so low that one could question the need for exhaustive testing of every single batch.
However, the research also highlights that testing is indispensable for catching unpredictable human errors. The key is intelligent, risk-based testing. For instance, testing is considered mandatory in specific situations 1 :
Furthermore, scientists are continuously working on simplifying and improving testing methods. For example, one study developed a streamlined quality control method for 99mTc-MAG3 that provided results comparable to official methods but was faster, used less solvent, and was less prone to operator error 6 .
This kind of innovation makes it easier for busy departments to maintain high safety standards without compromising efficiency.
| Total Preparations | Number of Failures | Failure Rate | Primary Causes of Failure |
|---|---|---|---|
| 2,280 | 6 | 0.26% | Gross technical/manual error (5), Insufficient incubation time (1) |
The quest to determine the right amount of radiochemical purity testing is a perfect example of science meeting practical reality. While advanced testing methods continue to evolve, the core principle remains unchanged: every patient deserves a diagnostic agent that is both safe and effective.
The extensive data shows that in a well-managed system, the inherent failure rate of the kits is negligible. The primary risk comes from the human element in the preparation process. Therefore, rigorous testing serves as the essential final check, a guardian at the gate ensuring that only the purest products reach patients.
As the field moves forward, the strategy will likely involve a combination of robust training, standardized procedures, and smarter, more efficient testing protocols—all in pursuit of the clearest images and the most accurate diagnoses.
This article was based on scientific studies published in journals including Acta Biomedica and the Journal of Nuclear Medicine Technology.