文摘
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)Serp>1p>,Leup>8p>,pan class="smallcaps">dpan>-Trpp>22p>,Tyrp>25p>]SS28} and its p>111p>In radioligand. [DOTA]LTT-SS28 exhibited a pansomatostatin-like profile binding with high affinity to all five hsst1鈥揾sst5 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 [p>111p>In-DOTA]LTT-SS28 showed good stability in the mouse bloodstream. It displayed strong and specific uptake in AR42J tumors 4 h postinjection (9.3 卤 1.6% ID/g vs 0.3 卤 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 卤 1.5, 4.88 卤 1.1, and <3% ID/g, respectively, with values of <0.5% ID/g during receptor blockade). In conclusion, the somatostatin mimic [p>111p>In-DOTA]LTT-SS28 specifically localizes in sst2-, sst3-, and sst5-expressing xenografts in mice showing promise for multi-sst1鈥搒st5 targeted tumor imaging.