Comparison of receptor affinity of Sc-nat-DOTA-TATE versus Ga-nat-DOTA-TATE

BACKGROUND: Sc-44 as a positron emitter can be an interesting alternative to Ga-68 (T-1/2 = 67.71 min) due to its longer half-life (T-1/2 = 3.97 h). Moreover, the beta-emitter 47Sc can be used for therapy when attached to the same biomolecule vectors. DOTA as a chelating agent has been proven suitable for the radiolabelling of peptides recognising tumour cell receptors in vivo with M3+ radiometals. DOTA-derivatized peptides have been successfully labelled with Y-90 and Lu-177 for therapy, and with Ga-68 for PET imaging. However, published data on Sc-44-labelled DOTA-biomolecules as potential PET radiotracers are still very limited. The aim of this study was to compare the affinity of Ga-nat-and Sc-nat-labelled DOTA-TATE to somatostatin receptors subtype 2 expressed in rat pancreatic cancer cell line AR42J. MATERIAL AND METHODS: The cold complexes of DOTA-TATE with Ga-nat and Sc-nat were synthesized and identified by HPLC and MS analysis and evaluated in vitro for competitive binding to cancer cell line AR42J expressing somatostatin receptors subtype 2 (sstr2). RESULTS: The IC50 values calculated from the displacement curve of [125I-Tyr11]-SST-14 were: 0.20 +/- 0.18, 0.70 +/- 0.20, 0.64 +/- 0.22 and 0.67 +/- 0.12 for Ga-nat-DOTA-TATE, Sc-nat-DOTA-TATE, DOTA-TATE, and [Tyr(11)]-SST-14 complexes, respectively, with the affinity lowering in the decreasing order: Ga-nat-DOTA-TATE > DOTA-TATE > Tyr(11)-SST-14 > Sc-nat-DOTA-TATE. CONCLUSIONS: The binding affinity of Ga-nat-DOTA-TATE appeared higher than that of Sc-nat-DOTA-TATE. Further in vitro and in vivo studies are needed to verify the influence of the chelated metal on the affinity and uptake of the respective radiolabelled compounds. This information might be crucial when the in vivo applications of peptides labelled with Ga-68 and Sc-44 for PET, as well as the use of Sc-47 for radiotherapy are considered.