Radiolabeled pansomatostatin-like analogues are expected to enhance the diagnostic sensitivity and to expand the clinical indications of currently applied sst2-specific radioligands. In this study, we present the somatostatin mimic [DOTA]LTT-SS28 {[(DOTA)Ser1,Leu 8,d-Trp22,Tyr25]SS28} and its 111In radioligand. [DOTA]LTT-SS28 exhibited a pansomatostatin-like profile binding with high affinity to all five hsst1-hsst5 subtypes (IC50 values in the lower nanomolar range). Furthermore, [DOTA]LTT-SS28 behaved as an agonist at hsst2, hsst3, and hsst5, efficiently stimulating internalization of the three receptor subtypes. Radioligand [111In-DOTA]LTT-SS28 showed good stability in the mouse bloodstream. It displayed strong and specific uptake in AR42J tumors 4 h postinjection (9.3 ± 1.6% ID/g vs 0.3 ± 0.0% ID/g during sst2 blockade) in mice. Significant and specific uptake was also observed in HEK293-hsst2-, HEK293-hsst3-, and HEK293-hsst5-expressing tumors (4.43 ± 1.5, 4.88 ± 1.1, and <3% ID/g, respectively, with values of <0.5% ID/g during receptor blockade). In conclusion, the somatostatin mimic [111In-DOTA]LTT-SS28 specifically localizes in sst2-, sst3-, and sst 5-expressing xenografts in mice showing promise for multi-sst 1-sst5 targeted tumor imaging.

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Journal Journal of Medicinal Chemistry
Maina, T, Cescato, R, Waser, B, Tatsi, A, Kaloudi, A, Krenning, E.P, … Reubi, J.-C. (2014). LTT-SS28, a first pansomatostatin radioligand for in vivo targeting of somatostatin receptor-positive tumors. Journal of Medicinal Chemistry, 57(15), 6564–6571. doi:10.1021/jm500581d