Table 3.
| Comp. | Sequence | t1/2 [h] b |
Uptake after 4 h [%] c |
KD [nM] d |
|---|---|---|---|---|
| BBN1 a | [177Lu]Lu-DOTA-PEG4-Gln-Trp-Ala-Val-Gly-His-Leu-Nle-NH2 | 5 | 27.7 | 2.0 ± 0.6 |
| BBN2 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-Ala-Val-Gly-His-Leu-NleΨ[Tz]H | 6 | 29.1 | 3.0 ± 0.5 |
| BBN3 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-Ala-Val-Gly-His-LeuΨ[Tz]Nle-NH2 | 60 | 0.2 | n.d. |
| BBN4 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-Ala-Val-Gly-HisΨ[Tz]Leu-Nle-NH2 | >100 | n.o. | n.d. |
| BBN5 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-Ala-Val-GlyΨ[Tz]His-Leu-Nle-NH2 | 17 | 28.3 | 3.1 ± 1.0 |
| BBN6 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-Ala-ValΨ[Tz]Gly-His-Leu-Nle-NH2 | 25 | 8.4 | 48.6 ± 11.5 |
| BBN7 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-AlaΨ[Tz]Val-Gly-His-Leu-Nle-NH2 | 16 | 24.5 | 5.9 ± 1.8 |
| BBN8 | [177Lu]Lu-DOTA-PEG4-Gln-TrpΨ[Tz]Ala-Val-Gly-His-Leu-Nle-NH2 | 8 | n.o. | n.d. |
| BBN9 | [177Lu]Lu-DOTA-PEG4-GlnΨ[Tz]Trp-Ala-Val-Gly-His-Leu-Nle-NH2 | 14 | n.o. | n.d. |
| BBN10 | [177Lu]Lu-DOTA-PEG4Ψ[Tz]Gln-Trp-Ala-Val-Gly-His-Leu-Nle-NH2 | 5 | 0.5 | n.d. |
| BBN11 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-AlaΨ[Tz]Val-GlyΨ[Tz]His-Leu-Nle-NH2 | 27 | 21.7 ± 0.2 | 25.6 ± 6.9 |
| BBN12 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-Ala-ValΨ[Tz]GlyΨ[Tz]His-Leu-Nle-NH2 | 40 | 3.5 ± 0.6 | >1000 |
| BBN13 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-AlaΨ[Tz]ValΨ[Tz]Gly-His-Leu-Nle-NH2 | 66 | 0.1 ± 0.1 | >1000 |
| BBN14 | [177Lu]Lu-DOTA-PEG4-Gln-Trp-AlaΨ[Tz]ValΨ[Tz]GlyΨ[Tz]His-Leu-Nle-NH2 | 61 | 0.3 ± 0.1 | >1000 |
a Reference compound. b Determined in blood serum at 37 °C. c Ratio of specific receptor-bound and cell-internalised compound expressed in % of administered dose. Expressed as the means ± SEM of at least two independent experiments. n.o.: not observed d Determined by receptor saturation binding assay on PC3 cells expressing GRPr. Expressed as the means ± SEM of at least two independent experiments. n.d.: not determined.