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BRAIN DEATH: RADIOCHEMICAL PURITY OF THE RADIOPHARMACEUTICAL 99mTc-HMPAO STABILIZED WITH COBALT

European Statement

Patient Safety and Quality Assurance

Author(s)

Diana Monteiro
Luísa Álvares
Sara Brandão Madureira
Patrocínia Rocha

Why was it done?

The confirmation of a clinical diagnosis of brain death requires the demonstration of the cessation of brainstem functions and their irreversibility. Therefore, when this evaluation is incomplete or unreliable, it is necessary to support this diagnosis using diagnostic tests such as brain perfusion SPECT. This is performed after the injection of the radiopharmaceutical technetium-99m hexamethylpropyleneamine oxime (99mTc-HMPAO) and by assessing the obtained images for the lack of cerebral perfusion to confirm the diagnosis.
Given the importance of reliable results, a high radiochemical purity of 99mTc-HMPAO is imperative in quality control to prevent false positives.

What was done?

Selection of a method to evaluate the radiochemical purity of 99mTc-HMPAO.

How was it done?

A literature review was conducted to select the most suitable method for the conditions existing in the institution. The research focused on the Summary of Product Characteristics (SmPC), the European Pharmacopoeia (Ph. Eur. 11.0), the United States Pharmacopeia (USP 42) and several published articles.
After selecting the method, three assays were performed to validate it.

What has been achieved?

For evaluating the radiochemical purity of 99mTc-HMPAO, both the SmPC and Ph.Eur. 11.0 recommend a combination of two thin-layer chromatography (TLC) methods with a high-dimension stationary phase, for which the institution does not have a chromatographic tank.
The USP 42 describes a combination of three TLC methods, using acetonitrile as the mobile phase, which is also unavailable at the institution.
In contrast, the miniaturized method by Fuente et al. uses two TLC methods, with a silica gel stationary phase and sodium chloride (0.9%) and methyl ethyl ketone as mobile phases. This method was selected given that the institution has the required phases, the stationary phase dimensions are suitable for the available chromatography tanks and the execution time for the assay is feasible.
For method validation, three assays were conducted, yielding values exceeding 80% (the reference value).
The selected method represents a rapid, reproducible and reliable alternative for evaluating the radiochemical purity of 99mTc-HMPAO. It was implemented in the institution in October 2022.

What next?

In the future, we aim to develop quality control methods for all radiopharmaceuticals in use at the institution, in order to guaranty the quality of all the exams performed.

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