Table 4. PSMA-Targeted Hybrid Tracers for Image-Guided Surgery.
| compound | receptor affinity (competitor) | tumor-to-background (time point, cell line, background tissue) | kidney-to-tumor (time point, cell line) | injected dose | biodistribution; time point | clearance pathway (time point, uptake clearance organs) | half-life | lipophilicity | plasma protein binding | optimized for entrance funnel? | imaging label (molecular weight) | imaging signature(s) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IRDye800CW-Lys-DOTA-Gly-urea-Lys111 | Ki = 1.2 ± 0.1 (Not described) | 11.58, 19.00, 18.22, 36.50 (1, 2, 5, 24 h, PC3-PIP, muscle) | 7.48, 7.29, 7.38, 3.29 (1, 2, 5, 24 h, PC3-PIP) | 0.1 nmol (370 MBq/nmol) | Yes; 1, 2, 5, 24 h | Renal (1 h, kidneys 104 ± 9.4%ID/g; liver 2.4 ± 0.1%ID/g, 2 h, kidneys 97.1 ± 13.0%ID/g, liver 2.2 ± 0.0%ID/g, 5 h, kidneys 121.7 ± 21.6%ID/g, liver 3.2 ± 1.2%ID/g, 24 h, kidneys 48.1 ± 17.7%ID/g, liver 3.1 ± 0.4%ID/g) | t1/2, rad = 67 h | LogP = 0.12a | Data not provided | Yes | DOTAGA, 111In (387 g/mol); IRDye800CW (983 g/mol) | γ (Eγ = 171.3, 245.4 keV); λabs = 774 nm, λex = 789 nm |
| 68Ga-PSMA I&F75 | IC50 = 10.5 ± 2.7 nM ((I-BA)-KuE) | 9.00 (1 h, LNCaP, muscle) | 23.56 (1 h, LNCaP) | 0.2 nmol (66 MBq/nmol) (2.0 nmol fluorescence imaging) | Yes; 1 h | Renal (1 h, kidneys 105.8 ± 22.7%ID/g, liver 0.9 ± 0.1%ID/g) | t1/2, rad = 1.1 h | LogP = −3.40 | 94% | Yes | DOTAGA, 68Ga (459 g/mol); Cy5 (625 g/mol) | γ (Eγ = 511 keV); λabs = 648 nm, λex = 664 nm |
| 68Ga-Glu-urea-Lys-HBED-CC-FITC113 | IC50 = 11.14 ± 1.16 nM (68Ga-EuK[(Ahx)]2-HBED-CC) | 1.06 (1 h, PC3-PIP, muscle) | 104 (1 h, PC3-PIP) | 60 pmol (17–33 MBq/nmol) 0.5 nmol (fluorescence imaging) | Yes; 1 h | Renal (1 h, kidneys 138 ± 39%ID/g, liver 1.7 ± 0.5%ID/g) | t1/2, rad = 1.1 h | logD = −2.98 ± 0.09 | Data not provided | Yesd | HBED-CC, 68Ga (499 g/mol); Fluorescein (346 g/mol) | γ (Eγ = 511 keV) λabs = 494 nm, λex = 512 nm |
| 68Ga-Glu-urea-Lys-HBED-CC-AlexaFluor488113 | IC50 = 13.32 ± 0.83 nM (68Ga-EuK[(Ahx)]2-HBED-CC) | 1.35 (1 h, PC3-PIP, muscle) | 69 (1 h, PC3-PIP) | 60 pmol (17–33 MBq/nmol) 0.5 nmol (fluorescence imaging) | Yes; 1 h | Renal (1 h, kidneys 125 ± 32%ID/g, liver 1.0 ± 0.3%ID/g) | t1/2, rad = 1.1 h | logD = −2.01 ± 0.39 | Data not provided | Yesd | HBED-CC, 68Ga (499 g/mol); AlexaFluor488 (505 g/mol) | γ (Eγ = 511 keV) λabs = 490 nm, λex = 525 nm |
| 68Ga-Glu-urea-Lys-HBED-CC-IRDye800CW113 | IC50 = 24.54 ± 5.70 nM (68Ga-EuK[(Ahx)]2-HBED-CC) | 1.15, 4.05, 12.88 (1, 2, 6 h, PC3-PIP, muscle) | 63.78, 15.11, 24.35 (1, 2, 6 h, PC3-PIP) | 60 pmol (17–33 MBq/nmol) 0.5 nmol (fluorescence imaging) | Yes; 1, 2, 6 h | Renal (1 h, kidneys 205 ± 56%ID/g, liver 2.8 ± 0.5%ID/g, 2 h, kidneys 120 ± 5.1%ID/g, liver 1.2 ± 0.1, 6 h, kidneys 160 ± 28%ID/g, liver 1.0 ± 0.2) | t1/2, rad = 1.1 h | logD = −2.21 ± 0.36 | Data not provided | Yesd | HBED-CC, 68Ga (499 g/mol); IRDye800CW (983 g/mol) | γ (Eγ = 511 keV) λabs = 774 nm, λex = 789 nm |
| 68Ga-Glu-urea-Lys-HBED-CC-DyLight800113 | IC50 = 21.41 ± 1.90 nM (68Ga-EuK[(Ahx)]2-HBED-CC) | 1.46 (1 h, PC3-PIP, muscle) | 52.11 (1 h, PC3-PIP) | 60 pmol (17–33 MBq/nmol) 0.5 nmol (fluorescence imaging) | Yes; 1 h | Renal (1 h, kidneys 221 ± 24%ID/g, liver 6.2 ± 1.1%ID/g) | t1/2, rad = 1.1 h | logD = −2.95 ± 0.03 | Data not provided | Yesd | HBED-CC, 68Ga (499 g/mol); DyLight800 (unknown) | γ (Eγ = 511 keV) λabs = 770 nm, λex = 794 nm |
| 99mTc-EuK-Cy5-mas3114 | IC50 = 175.3 ± 61.6 nM ((I-BA)-KuE) | 18.95 ± 14.66 (2 h, LNCaP, muscle) | 2.99 (2 h, LNCaP) | 1 nmol (40 MBq/nmol) | Yes; 2 h | Renal (2 h, kidneys 9.0 ± 5.6%ID/g, liver 1.8 ± 0.8%ID/g) | t1/2, rad = 6.5 h | LogP = −2.13 ± 0.10 | 88% | Yes | mas3, 99mTc (408 g/mol); Cy5 (523 g/mol) | γ (Eγ = 140.5 keV); λabs = 648 nm, λex = 664 nm |
| 99mTc-EuK-(SO3)Cy5-mas3114 | IC50 = 19.2 ± 5.8 nM ((I-BA)-KuE) | 5157 ± 949 (2 h, LNCaP, muscle) | 1.20 (2 h, LNCaP) | 1 nmol (40 MBq/nmol) | Yes; 2 h | Renal (2 h kidneys 18.4 ± 8.5%ID/g, liver 0.6 ± 0.5%ID/g) | t1/2, rad = 6.5 h | LogP = −2.86 ± 0.05 | 85% | Yes | mas3, 99mTc (408 g/mol); Cy5 (602 g/mol) | γ (Eγ = 140.5 keV); λabs = 648 nm, λex = 664 nm |
| 99mTc-EuK-Cy5(SO3)-mas3114 | IC50 = 118.8 ± 117.4 nM ((I-BA)-KuE) | 0.46 ± 0.28 (2 h, LNCaP, muscle) | 0.00 (2 h, LNCaP) | 1 nmol (40 MBq/nmol) | Yes; 2 h | Renal (2h kidneys 10.5 ± 12.8%ID/g, liver 0.5 ± 0.1%ID/g) | t1/2, rad = 6.5 h | LogP = −2.70 ± 0.01 | 87% | Yes | mas3, 99mTc (408 g/mol); Cy5 (602 g/mol) | γ (Eγ = 140.5 keV); λabs = 648 nm, λex = 664 nm |
| 99mTc-EuK-(Ar)Cy5-mas3114 | IC50 = 113.1 ± 35.9 nM ((I-BA)-KuE) | 172 ± 84.95 (2 h, LNCaP, muscle) | 4.51 (2 h, LNCaP) | 1 nmol (40 MBq/nmol) | Yes; 2 h | Renal (2 h, kidneys 15.6 ± 20.0%ID/g, liver 3.3 ± 2.2%ID/g) | t1/2, rad = 6.5 h | LogP = −1.75 ± 0.10 | 91% | Yes | mas3, 99mTc (408 g/mol); Cy5 (612 g/mol) | γ (Eγ = 140.5 keV); λabs = 648 nm, λex = 664 nm |
| 99mTc-EuK-Cy5(Ar)-mas3114 | IC50 = 164.4 ± 76.9 nM ((I-BA)-KuE) | 5.79 ± 0.86 (2 h, LNCaP, muscle) | 2.87 (2 h, LNCaP) | 1 nmol (40 MBq/nmol) | Yes; 2 h | Renal (2 h, kidneys 11.9 ± 12.3%ID/g, liver 9.6 ± 6.8%ID/g) | t1/2, rad = 6.5 h | LogP = −1.84 ± 0.06 | 89% | Yes | mas3, 99mTc (408 g/mol); Cy5 (612 g/mol) | γ (Eγ = 140.5 keV); λabs = 648 nm, λex = 664 nm |
| 18F-(SO3)Cy3(SO3)-EuK115 | EC50 = 10.3 ± 0.7 nM (Unlabeled(SO3)Cy3(SO3)-EuK) | 128 (2 h, PC3-PIP, blood) | 0.06 (2 h, PC3-PIP) | 2.5 nmol (7.0 ± 1.9 MBq/nmol) | Yes; 2 h | Renal (2 h, kidneys 1.0 ± 0.5%ID/g, liver 0.1 ± 0.0%ID/g) | t1/2, rad = 1.8 h | LogP = 1.02a | Data not provided | No | 18F (278 g/mol); Cy3 (682 g/mol) | β (Emaxβ+ = 634 keV) λabs = 550 nm, λex = 570 nm |
a
Values were calculated by using ChemAxon’s Chemicalize plugin.
b
Estimated from graph.
c
Estimated from scale bar. AU = arbitrary units.
d
No spacer as opposed to parental compound PSMA-11.78