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

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• 作者：Theodosia Maina ; Renzo Cescato ; Beatrice Waser ; Aikaterini Tatsi ; Aikaterini Kaloudi ; Eric P. Krenning ; Marion de Jong ; Berthold A. Nock ; Jean Claude Reubi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：August 14, 2014
• 年：2014
• 卷：57
• 期：15
• 页码：6564-6571
• 全文大小：307K
• ISSN：1520-4804

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)Ser¹,Leu⁸,d-Trp²²,Tyr²⁵]SS28} and its ¹¹¹In 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 [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 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 [¹¹¹In-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.