TABLE 1.

Chemical Structure and IC50 Values of sst2 Antagonists Based on JR10, JR11, and LM3 Family and Their Metallated Conjugates

IC50 (nM)
Code numberChemical structuresst1sst2sst3sst4sst5
DOTA-JR11*DOTA-Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0000.72 ± 0.12>1,000>1,000>1,000
Ga-DOTA-JR11[natGa]-DOTA-Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,00029 ± 2.7>1,000>1,000>1,000
Y-DOTA-JR11[natY]-DOTA-Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0000.47 ± 0.05>1,000>1,000>1,000
Lu-DOTA-JR11[natLu]-DOTA-Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0000.73 ± 0.15>1,000>1,000>1,000
Cu-DOTA-JR11[natCu]-DOTA-Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,00016 ± 1.2>1,000>1,000>1,000
In-DOTA-JR11[natIn]-DOTA-Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0003.8 ± 0.7>1,000>1,000>1,000
NODAGA-JR11NODAGA-Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0004.1 ± 0.2>1,000>1,000>1,000
Ga-NODAGA-JR11[natGa]-NODAGA-Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0001.2 ± 0.2>1,000>1,000>1,000
DOTA-JR10†DOTA-p-NO2-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0000.62 ± 0.21>1,000>1,000>1,000
Ga-DOTA-JR10[natGa]-DOTA-p-NO2-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0008.9 ± 2.2>1,000>1,000>1,000
In-DOTA-JR10[natIn]-DOTA-p-NO2-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0002.3 ± 0.5>1,000>1,000>1,000
Lu-DOTA-JR10[natLu]-DOTA-p-NO2-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0001.2 ± 0.2>1,000>1,000>1,000
NODAGA-JR10NODAGA-p-NO2-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,00023.0 ± 1.5>1,000>1,000>1,000
Ga-NODAGA-JR10[natGa]-NODAGA-p-NO2-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0006.5 ± 0.5>1,000>1,000>1,000
DOTA-LM3DOTA-p-Cl-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0000.39 ± 0.05>1,000>1,000>1,000
Ga-DOTA-LM3‡[natGa]-DOTA-p-Cl-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,00012.5 ± 4.3>1,000>1,000>1,000
In-DOTA-LM3[natIn]-DOTA-p-Cl-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0001.3 ± 0.1>1,000>1,000>1,000
Ga-NODAGA-LM3‡[natGa]-NODAGA-p-Cl-Phe-c[d-Cys-Tyr-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH2>1,0001.3 ± 0.2>1,000>1,000>1,000
Reference agonist, Ga-DOTATATE§[natGa]-DOTA-d-Phe-c[Cys-Tyr-d-Trp-Lys-Thr-Cys]-Thr>1,0000.2 ± 0.04>1,000300 ± 140377 ± 18

  • ↵* Corresponds to peptide 31 in Cescato et al. (11).

  • ↵† Corresponds to peptide 3 in Cescato et al. (11).

  • ↵‡ Described in Fani et al. (13).

  • ↵§ Described in Reubi et al. (1).

  • Data are expressed in nmol/L (mean ± SEM; n ≥ 3).