Evaluation of a New 177Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5.
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11 septembre 2020
- doi: 10.3390/molecules25184155
- issn: 1420-3049
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Growth hormone release inhibiting factor SRIH (Hormone) Thyrotropin release inhibiting factor Somatotropin release inhibiting hormone Follicle stimulating hormone release inhibiting factor Growth hormone inhibitory hormoneCiter ce document
R. Mansi et al., « Evaluation of a New 177Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5. », Serveur académique Lausannois, ID : 10.3390/molecules25184155
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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-NH 2 ), having subnanomolar affinity for SST2 and SST5, labeled with [ 177 Lu]Lu 3+ 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. nat Lu-DOTA-ST8950 showed nanomolar affinity for both subtypes (IC 50 (95% confidence interval): 0.37 (0.22-0.65) nM for SST2 and 3.4 (2.3-5.2) for SST5). The biodistribution of [ 177 Lu]Lu-DOTA-ST8950 was influenced by the injected mass, with 100 pmol demonstrating lower background activity than 10 pmol. [ 177 Lu]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, [ 177 Lu]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.