[(111)]n-DOTA]LTT-SS28, a First Pansomatostatin Radioligand for in Vivo Targeting of Somatostatin Receptor-Positive Tumors

Radio labeled pansomatostatin-like analogues are expected to enhance the diagnostic sensitivity and to expand the clinical indications of currently applied sst(2)-specific radioligands. In this study, we present the somatostatin mimic [DOTA]LTT-SS28 {[(DOTA)-Ser(1),Leu(8),D-Trp(22),Tyr(25)]SS28} and its In-111 radioligand. [DOTA]LTT-SS28 exhibited a pansomatostatin-like profile binding with high affinity to all five hsst(1)-hsst(5) subtypes (IC50 values in the lower nanomolar range). Furthermore, [DOTA]LTT-SS28 behaved as an agonist at hsst(upsilon), hsst(3), and hsst(5), efficiently stimulating internalization of the three receptor subtypes. Radioligand [In-111-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% 1D/g during sst(2) blockade) in mice. Significant and specific uptake was also observed in HEK293-hsst(2)-, HEK293-hsst(3)-, and HEK293-hsst(5)-expressing tumors (4.43 +/- 1.5, 4.88 +/- 1.1, and <3% ID/g, respectively, with values of <0.596 1D/g during receptor blockade). In conclusion, the somatostatin mimic [In-111-DOTA]LTT-SS28 specifically localizes in sst(2)-, sst(3)-, and sst(5)-expressing xenografts in mice showing promise for multi-sst(1)-sst(5) targeted tumor imaging.