ABSTRACT
In vivo instability of radiolabelled NPs, which may result in detachment of the radionuclide, can have a significant impact on the interpretation and conclusions of imaging studies. Evaluation of the in vivo stability of radiolabelled NPs is therefore a critical step in radiopharmaceutical development. When dealing with small molecules, assessment of stability usually requires blood sampling and processing. Sample processing involves the isolation of the plasma component of blood by centrifugation and subsequent analysis using instrumental analytical techniques such as high performance liquid chromatography (HPLC) with radiometric detection or (instant) thin layer chromatography (TLC/ITLC). When dealing with macromolecules such as proteins or antibodies, size exclusion chromatography (SEC) or gel electrophoresis are often used. Although the identification of the radioactive metabolites or detached radiolabelled species is often very challenging, the percentage of radioactivity present as the parent compound can usually be determined. In principle, blood sampling followed by plasma isolation and further analysis can be regarded as a suitable strategy for the assessment of the stability of radiolabelled NPs. However, three main drawbacks to this approach require careful consideration: (i) NPs are not easily isolated from blood samples; (ii) NPs usually have long residence times in the body, and when used with radioisotopes with appropriate half-lives, imaging studies can extend over days or even weeks; in this scenario, radiochemical stability must at least be assessed after a time gap equivalent to the duration of the proposed imaging studies; and (iii) the stability of the NPs themselves is very difficult to determine.
