Table 2.
Internalization and externalization characteristics of [177Lu]PentixaTher and selected linker-modified analogs. Total cellular uptake of the respective radioligands (1 nM) and the percentage of internalized ligand were determined using hCXCR4 expressing Chem-1 cells (100,000 cells/well, 60 min at 37°C). Ligand release and recycling within 60 min at 37°C (following internalization for 120 min at 37°C) was determined in the same cell line under conditions allowing (medium only) and inhibiting ligand recycling (10 µM AMD3100).
| Peptide | Cellular uptake | Cellular retention | ||
|---|---|---|---|---|
| Total uptake [% of applied activity] |
Internalized [% of total uptake] |
Recycling inhibited [% of cellular activity at t=0] |
Recycling allowed [% of cellular activity at t=0] |
|
| [177Lu]PentixaTher (entry 2) | 10.0 ± 1.3 | 47 ± 16 | 21.8 ± 0.8 | 41.0 ± 1.0 |
| [177Lu]DOTA-ABA-iodoCPCR4 (entry 3) | 17.4 ± 1.9 | 78 ± 11 | 25.1 ± 0.4 | 41.3 ± 0.6 |
| [177Lu]DOTA-r-G-ABA-CPCR4 (entry 11) | 26.4 ± 1.6 | 51 ± 6 | 21.8 ± 0.4 | 82.3 ± 0.8 |
| [177Lu]DOTA-r-G-ABA-iodoCPCR4 (entry 12) | 38.3 ± 2.0 | 90 ± 8 | 21.8 ± 0.8 | 80.5 ± 2.2 |
| [177Lu]DOTA-r-a-ABA-CPCR4 (entry 13) | 43.1 ± 1.1 | 65 ± 6 | 14.9 ± 1.1 | 93.1 ± 6.3 |
| [177Lu]DOTA-r-a-ABA-iodoCPCR4 (entry 14) | 40.4 ± 1.5 | 91 ± 4 | 27.6 ± 1.0 | 85.8 ± 1.0 |
All data are corrected for non-specific binding/internalization in the presence of 100 μM AMD3100 and are expressed as mean ± SD (n = 3).