Detailed analysis concerning the biodistribution and metabolism of human calcitonin-derived cell-penetrating peptides

The interest in using small peptides for therapeutic and diagnostic in vivo applications is based on several advantageous features such as good penetration into tissues and rapid clearance from the body. Because of their size, they can easily be synthesized chemically. The recently discovered cell-penetrating peptides (CPP) and among them CPP derived from the native peptide hormone human calcitonin (hCT) could meet these requirements. Therefore, they are nowadays widely used as delivery vectors for a variety of bioactive molecules. However, the knowledge about the distribution and metabolism of CPP in vivo is very limited. Hence, evaluation of the pharmacological features of any promising peptide is a crucial challenge in its development process. Herein, we studied the in vivo radiopharmacology of Ga-68 radiolabeled DOTA-modified, hCT-derived CPP in rats using small animal PET. Furthermore, the arterial blood at different time points and urine were analyzed for radiometabolites. It was shown that D-amino acid modifications of the sequence hCT(9-32) resulted in an increased in vivo stability and lower retention in the kidney cortex of this peptide.