Endocrine Abstracts

The common perception is that receptor targeting peptide radiopharmaceuticals of high affinity should be prepared and administered in high specific radioactivity and thus low peptide content in order to assure high contrast uptake in the target tissue. However, both pre-clinical and clinical studies have demonstrated complexity of the translation of the observations in vitro to in vivo pharmacokinetics. The investigation of the phenomenon for clinically used radiopharmaceuticals is of outmost importance and is exemplified using clinically established [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-DOTATATE. The affinity and biodistribution of [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-DOTATATE were compared in vitro and in vivo both pre-clinically and clinically. The influence of the injected peptide mass was studied pre-clinically and clinically for [⁶⁸Ga]Ga-DOTATOC. The choice of the specific radioactivity value of the radiopharmaceutical depends on the application. Determination of the affinity in vitro by frozen tissue section autoradiography was possible with [⁶⁸Ga]Ga-DOTATOC only of highest specific radioactivity. On the contrary in vivo in humans the target tissue uptake improved with lower specific radioactivity. The clinical study indicated importance of the optimization of the administered peptide amount in order to assure accurate quantification of the target receptors and subsequent radiotherapy planning. The interpatient variation stressed the importance of the individualized treatment approach. The effect of affinity difference between [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-DOTATATE on the targeting properties could not be detected in vivo in rats and humans. However, there was a slight thought statistically significant difference in some healthy organs, e.g. liver and gallbladder as well as excretion.The pre-clinical and clinical studies demonstrated necessity for the optimization of the specific radioactivity of the radiopharmaceuticals in each particular case and for the personalized patient management. Difference in affinity determined in cell cultures might not be essential in vivo in terms of radiopharmaceutical biodistribution, targeting and imaging properties.