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

Abstract

BACKGROUND: ⁴⁴Sc as a positron emitter can be an interesting alternative to ⁶⁸Ga (T_½ = 67.71 min) due to its longer half-life (T_½ = 3.97 h). Moreover, the b– 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 ⁹⁰Y and ¹⁷⁷Lu for therapy, and with ⁶⁸Ga for PET imaging. However, published data on ⁴⁴Sc-labelled DOTA-biomolecules as potential PET radiotracers are still very limited. The aim of this study was to compare the affinity of ^natGa- and ^natSc-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 ^natGa and ^natSc 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 ^natGa-DOTA-TATE, ^natSc-DOTA-TATE, DOTA-TATE, and {Tyr¹¹}-SST-14 complexes, respectively, with the affinity lowering in the decreasing order: ^natGa-DOTA-TATE > DOTA-TATE > Tyr¹¹-SST-14 > ^natSc-DOTA-TATE.
CONCLUSIONS: The binding affinity of ^natGa-DOTA-TATE appeared higher than that of ^natSc-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 ⁶⁸Ga and ⁴⁴Sc for PET, as well as the use of 47Sc for radiotherapy are considered.
Nuclear Med Rev 2011; 14, 2: 85–89