Specific Labeling With Potent Radiolabels Alters the Uptake of Cell-Penetrating Peptides

Radiolabeled peptides play an important role in radiopharmacy not only as tumor markers but also as transport vectors. Therefore, cell-penetrating peptides (CPP) may serve as very effective delivery tools, as well. Recently, CPP based on the human hormone calcitonin (hCT) have been developed. Especially, branched hCT-peptide sequences turned out to have highly efficient internalization capacities. Labeling these peptides with radionuclides would generate promising new tools for imaging and therapy applications in radiopharmacy. However, the influence of the metal complexation on the internalization capacity of CPP has not been elucidated yet in detail. In this study we quantified the uptake of Ga-DOTA modified hCT-carrier peptides in HeLa cells by using atomic absorption spectroscopy (AAS) and compared the results to the uptake of fluorescently-labeled peptides. Interestingly, we measured different uptake rates depending on the attached label. Unexpectedly, modification with a Ga-DOTA complex can have tremendous effects on the uptake efficiency. The results of these studies support the need of detailed analysis of each carrier peptide/cargo construct, especially in the field of metal complex modified CPR. (C) 2009 Wiley Periodicals, Inc. Biapolymers (Pept Sci) 92: 445-451, 2009.