Radiolabeling of DOTATOC with the long-lived positron emitter 44Sc

The positron-emitting radionuclide 44Sc with a half-life of 3.97 h and a β+ branching of 94.3% is of potential interest for clinical PET. As so far it is available from a 44Ti/44Sc generator in Mainz, where long-lived 44Ti decays to no-carrier-added (nca) 44Sc. The 44Sc is a trivalent metal cation and should be suitable for complexation with many well established bifunctional chelators conjugated to peptides or other molecular targeting vectors. Thus, the aim of this work was to investigate the potential of 44Sc for labeling of DOTA-conjugated peptides. DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) was used as a model molecule to study and optimize labeling procedure. Reaction parameters such as buffer conditions, concentration of peptide, pH range, reaction temperature and time were optimized. Addition of 21 nmol of DOTATOC to 44Sc in ammonium acetate buffer pH 4.0 provided labeling yields >98% within 25 min of heating in an oil-bath at 95 °C. This time can be reduced to 3 min only by applying microwave supported heating. 44Sc-DOTATOC was found to be stable in 0.9% NaCl, PBS pH 7.4, fetal calf and human serums, and also in the presence of competing metal cations (Fe3+, Ca2+, Cu2+, Mg2+), as well as other ligand competitors, like EDTA and DTPA, even after almost 25 h incubation at 37 °C. Present study shows that nca 44Sc forms stable complexes with the macrocyclic ligand DOTA and that 44Sc-DOTATOC and analog targeting vectors may be synthesized for further preclinical and clinical investigations.

► Labeling of somatostatin analouges with positron emitter 44Sc was tested. ► DOTATOC was labeled with 44Sc isotope. ► Optimal conditions for 44Sc-DOTATOC synthesis were found. ► Stability of 44Sc-DOTATOC was investigated in details in different solutions.