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Evaluation of a New$ ^{177}$Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5
| Content Provider | MDPI |
|---|---|
| Author | Mansi, Rosalba Nicolas, Guillaume Pozzo, Luigi Del Abid, Karim Grouzmann, Eric Fani, Melpomeni |
| Copyright Year | 2020 |
| Description | Targeted radionuclide therapy of somatostatin receptor (SST)-expressing tumors is only partially addressed by the established somatostatin analogs having an affinity for the SST subtype 2 (SST2). Aiming to target a broader spectrum of tumors, we evaluated the bis-iodo-substituted somatostatin analog ST8950 ((4-amino-3-iodo)-d-Phe-c[Cys-(3-iodo)-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2), having subnanomolar affinity for SST2 and SST5, labeled with [177Lu]Lu3+ via the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Human Embryonic Kidney (HEK) cells stably transfected with the human SST2 (HEK-SST2) and SST5 (HEK-SST5) were used for in vitro and in vivo evaluation on a dual SST2- and SST5-expressing xenografted mouse model. natLu-DOTA-ST8950 showed nanomolar affinity for both subtypes (IC50 (95% confidence interval): 0.37 (0.22–0.65) nM for SST2 and 3.4 (2.3–5.2) for SST5). The biodistribution of [177Lu]Lu-DOTA-ST8950 was influenced by the injected mass, with 100 pmol demonstrating lower background activity than 10 pmol. [177Lu]Lu-DOTA-ST8950 reached its maximal uptake on SST2- and SST5-tumors at 1 h p.i. (14.17 ± 1.78 and 1.78 ± 0.35%IA/g, respectively), remaining unchanged 4 h p.i., with a mean residence time of 8.6 and 0.79 h, respectively. Overall, [177Lu]Lu-DOTA-ST8950 targets SST2-, SST5-expressing tumors in vivo to a lower extent, and has an effective dose similar to clinically used radiolabeled somatostatin analogs. Its main drawbacks are the low uptake in SST5-tumors and the persistent kidney uptake. |
| Starting Page | 4155 |
| e-ISSN | 14203049 |
| DOI | 10.3390/molecules25184155 |
| Journal | Molecules |
| Issue Number | 18 |
| Volume Number | 25 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-09-11 |
| Access Restriction | Open |
| Subject Keyword | Molecules Oncology Radiolabeled Somatostatin Analogs Sst2 Sst5 Lu-177 Targeted Radionuclide Therapy Neuroendocrine Tumors Dual-tumor Mouse Model |
| Content Type | Text |
| Resource Type | Article |
