Radiolabeling of DOTATOC with 44T/44Sc generator-derived 44Sc

Objectives The radionuclide 44Sc with 3.97 h half-life and 94.3% positron branching is of potential interest for clinical PET. It is available from a 44Ti/44Sc generator. 44Sc(III) may be used to synthesize radiopharmaceuticals analogously to currently used radionuclides such as 68Ga, 111In, 90Y or 177Lu. A key question was whether the coordination chemistry of Sc(III) is equivalent to established tetraaza- or triaza-based macrocyclic ligands. The aim of this work was to investigate, as a proof-of-principle, 44Sc-labeling of DOTA-conjugated peptides.

Methods 21 nmol of DOTATOC in 2 mL of a processed 44Sc eluate in ammonium acetate buffer pH = 4.0 were used. Reaction buffer conditions, pH range, temperature and time were optimized. Stability of 44Sc-DOTATOC was analyzed in challenge assays using excess of other metals (Fe3+, Ca2+, Cu2+, Mg2+) or other ligands like EDTA and DTPA.

Results Labeling was >98% within 25 minutes of heating in an oil-bath at 95°C or within 3 min only by applying microwave-supported heating. Isolation of the pure 44Sc-labeled product is performed on C-18 mini-cartridges (Strata-X) and results in radiochemically pure 44Sc-DOTATOC in 400 µL of pure ethanol. 44Sc-DOTATOC at 130 MBq activity is stable in ethanolic solution, 0.9% NaCl, phosphate buffer with sodium chloride (PBS pH = 7.4), and also in the presence of metal cations as well as other ligands.

Conclusions Incorporation of 44Sc(III) into DOTATOC is almost quantitative at pH 4.0. This radiochemically pure and chemically stable 44Sc-DOTATOC may allow follow-up research on PET/CT imaging making advantage of the 3.97 h half-life of this positron emitter. A specific field may be the application of 44Sc tracers matching therapeutic applications of analogue compounds labeled with e.g. 90Y or 177Lu, but also with the β- emitter 47Sc