Comparison of receptor affinity of natSc-DOTA-TATE versus natGa-DOTA-TATE.
BACKGROUND
44Sc as a positron emitter can be an interesting alternative to 68Ga (T½=67.71 min) due to its longer half-life (T½=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.


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.
National Centre for Nuclear Research, Radioisotope Centre POLATOM, Otwock, Poland.
Eftychia
E
Koumarianou
Dariusz
D
Pawlak
Agnieszka
A
Korsak
Renata
R
Mikolajczak
D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics*; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D020128:Inhibitory Concentration 50; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011868:Radioisotopes / Q000493:pharmacokinetics*; D051381:Rats; D017481:Receptors, Somatostatin / Q000187:drug effects*; D012538:Scandium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002614:Chelating Agents; D005710:Gallium Radioisotopes; D011868:Radioisotopes; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2; D012538:Scandium