EANM guideline for harmonisation on molar activity or specific activity of radiopharmaceuticals: impact on safety and imaging quality

Abstract

This guideline on molar activity (Am) and specific activity (As) focusses on small molecules, peptides and macromolecules radiolabelled for diagnostic and therapeutic applications. In this guideline we describe the definition of Am and As, and how these measurements must be standardised and harmonised. Selected examples highlighting the importance of Am and As in imaging studies of saturable binding sites will be given, and the necessity of using appropriate materials and equipment will be discussed. Furthermore, common Am pitfalls and remedies are described. Finally, some aspects of Am in relation the emergence of a new generation of highly sensitive PET scanners will be discussed.

Optimization of Precursor Preparation in PSMA-11 Radiolabeling to Obtain a Highly Reproducible Radiochemical Yield

“…Table 3 shows that the % RCY decrease corresponds to an increase in the unspecified impurities into [ 68 Ga]Ga-PSMA-11 preparations (see residual in C18 cartridge), as well as to an increase in gallium-68 in colloidal and ionic forms and, consequently, to a decrease in % RCP close to the lower limit of the pharmacopeia specifications (Method A). Indeed, for radiotracers clinical use, it is mandatory to obtain radiochemical purities ≥ 95% [ 6 ]. This is shown in Figure 3 , where the decrease of blue bars (% RCY) corresponds to a decrease of red bars (% RCP).…”

“…The contamination from starting materials during the radiosynthesis can dilute the radiolabelled compound with its non-labeled analog and cause a decrease of % RCY [ 6 ].…”

“…However, a high molar activity (A m ) or specific activity (A s ) of the radiopharmaceutical is preferred, and it is known that if the precursor (ligand) increases, the molar activity decreases [ 6 ].…”

“…Recent EANM guidelines on harmonization of the molar activity or specific activity of radiopharmaceuticals reported that in the case of radiometallation of peptides the presence in the peptide precursor of metal ion contaminants indirectly affects A m by necessitating higher amounts of peptide precursor to achieving high radionuclide incorporation. For such radiotracers, we are therefore normally referring to the apparent A m , empirically determined by dividing the amount of radioactivity present in an exact volume of the final formulation by the amount of peptide precursor used in the labeling process in mol (or µmol) [ 6 , 7 ].…”

Radiolabeled PSMA Inhibitors

“…This was confirmed in healthy volunteers determining biodistribution and radiation dosimetry data (NCT03995888) and in a larger cohort of patients [ 84 , 195 , 196 , 197 ]. The molar activity of [ 18 F]Ga-rh-PSMA-7.3 had a minor influence on the biodistribution [ 198 , 199 ]. Three clinical trials using [ 18 F]Ga-rh-PSMA-7.3 are either ongoing or will commence in the near future (NCT04978675/NCT04186819/NCT04186845).…”