Background
Nuclide | Half-life | Radiation energy | Ligand | Chelator | Application | Refs. |
---|---|---|---|---|---|---|
44Sc | 4.04 h | Eβ+
av = 632 keV Eγ = 1157 keV* | PSMA-617 | DOTA | PET (β+-radiation) | Evaluated in this study |
177Lu | 6.65 days | Eβ−
av = 134 keV Eγ = 113 keV, 208 keV | PSMA-617 | DOTA | Therapy/SPECT (β−/γ-radiation) | |
68Ga | 68 min | Eβ+
av = 830 keV Eγ = 1077 keV** | PSMA-617 PSMA-11 | DOTA HBED-CC | PET (β+-radiation) | [21] |
Methods
PSMA-ligands and radionuclides
Radiolabeling of PSMA-617 and PSMA-11
Determination of n-octanol/PBS distribution coefficients
Cell culture
Cell experiments
Tumor mouse model
Biodistribution studies
Imaging studies
Results
Radiolabeling and in vitro evaluation of PSMA-targeted radioligands
Radioligand | LogD valuesa
| Relative PSMA-binding affinityb
|
---|---|---|
44Sc-PSMA-617 | −4.21 ± 0.04 | 1.2 |
177Lu-PSMA-617 | −4.18 ± 0.06 | 1.0 |
68Ga-PSMA-617 | −4.30 ± 0.10 | 0.5 |
68Ga-PSMA-11 | −4.82 ± 0.07 | 0.4 |
Cell internalization studies of PSMA radioligands
Biodistribution studies in tumor-bearing mice
15 min after injection | ||||
PSMA-ligand |
44Sc-PSMA-617 |
177Lu-PSMA-617 |
68Ga-PSMA-617 |
68Ga-PSMA-11 |
Tumor-to-blood | 5.38 ± 0.90 | 4.45 ± 0.66 | 4.15 ± 0.24 | 6.10 ± 1.84 |
Tumor-to-liver | 18.8 ± 5.02 | 20.4 ± 5.48 | 6.02 ± 0.59 | 15.3 ± 3.96 |
Tumor-to-kidney | 0.97 ± 0.21 | 1.06 ± 0.14 | 1.26 ± 0.25 | 0.41 ± 0.14 |
30 min after injection | ||||
44Sc-PSMA-617 |
177Lu-PSMA-617 |
68Ga-PSMA-617 |
68Ga-PSMA-11 | |
Tumor-to-blood | 17.6 ± 1.23 | 16.0 ± 3.52 | 16.9 ± 4.22 | 20.5 ± 6.40 |
Tumor-to-liver | 55.6 ± 7.36 | 53.1 ± 6.68 | 19.0 ± 2.32 | 31.7 ± 2.48 |
Tumor-to-kidney | 1.60 ± 0.22 | 2.09 ± 0.24 | 3.62 ± 0.81 | 0.58 ± 0.10 |
2 h after injection | ||||
44Sc-PSMA-617 |
177Lu-PSMA-617 |
68Ga-PSMA-617 |
68Ga-PSMA-11 | |
Tumor-to-blood | >200 | >200 | >200 | >200 |
Tumor-to-liver | >200 | >200 | 35.2 ± 9.94 | 71.3 ± 7.48 |
Tumor-to-kidney | 7.98 ± 1.71 | 11.6 ± 0.87 | 15.9 ± 3.26 | 0.69 ± 0.12 |