Table 2. Visible to Far-Red Fluorescent Imaging Agents for PSMA-Targeted Fluorescence-Guided Surgery.
| compound | receptor affinity (competitor) | tumor uptake (time point, cell line) | kidney uptake (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 | imaging signature(s) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CYUE-Rhodamine B98 | kD = 88 nM (2-PMPA) | No ex vivo quantification, no scale bars | No ex vivo quantification, no scale bars | No in/ex vivo experiments performed | No in/ex vivo experiments performed | No in/ex vivo experiments performed | No in/ex vivo experiments performed | LogP = −0.37a | Data not provided | Yes | Rhodamine-B (427 g/mol) | λabs = 510 nm, λem = 565 nm |
| DUPA-Dylight 68046 | kD = 33 nM (2-PMPA) | No ex vivo quantification, no scale bars | No ex vivo quantification, no scale bars | 10 nmol | No ex vivo quantification, no scale bars | No ex vivo quantification, no scale bars | Data not provided | LogP = 1.38a | Data not provided | Yes | DyLight 680 (790 g/mol) | λabs = 682 nm, λem = 715 nm |
| DUPA-Alexa Fluor 64746 | kD = 4.5 nM (2-PMPA) | No ex vivo quantification, no scale bars | No ex vivo quantification, no scale bars | 10 nmol | No ex vivo quantification, no scale bars | No ex vivo quantification, no scale bars | Data not provided | Fluorophore structure not available | Data not provided | Yes | AlexaFluor 647 (853 g/mol) | λabs = 650 nm, λem = 670 nm |
| PSMA-1-Cy5.599 | IC50 = 2.1 ± 0.1 nM (Glutamate-ureido-cysteine) | 5.08%ID (24 h, PC3-PIP) 2, 3, 7, 17, 18, 16, 51, 51, 50, 43, 41, 41 AUb (at 0.8, 0.17, 0.5, 1, 2, 6, 8, 24, 48, 72, 96, and 120 h PC3-PIP (in vivo)) | 0.025 AUc (120 h, PC3-PIP) | 1 nmol | Qualitative; 0.8, 0.17, 0.5, 1, 2, 4, 6, 8, 24, 48, 72, 96, and 120 h (in vivo); Qualitative; 120 h (ex vivo) | Renal (120 h, kidneys 0.025 AUc, liver 0.01 AUc) | Data not provided | LogP = −1.02 ± 0.23 | Data not provided | Yes | Cy5.5 (567 g/mol) | λabs = 675 nm, λem = 694 nm |
| Cy5.5–1101 | ki = 90 ± 40 pM (NAAG) | 30000 AUc (24 h, PC3-PIP) | 60000 AUc (24 h, PC3-PIP) | 1 nmol | Qualitative; 1, 4, 24 h | Renal (24 h, kidneys 60000 AUc, liver 10000 AUc) | Data not provided | LogP = 0.12a | Data not provided | Yes | Tetrakis sulfonate Cy5.5 (897 g/mol) | λabs = 675 nm, λem = 694 nm |
| Cy5.5–2101 | ki = 50 ± 20 pM (NAAG) | 50000 AUc (24 h, PC3-PIP) | 50000 AUc (24 h, PC3-PIP) | 1 nmol | Qualitative; 1, 4, 24 h | Renal (24 h, kidneys 50000 AUc, liver 10000 AUc) | Data not provided | LogP = −1.08a | Data not provided | Yes | Tetrakis sulfonate Cy5.5 (897 g/mol) | λabs = 675 nm, λem = 694 nm |
| Cy5.5–3101 | ki = 50 ± 2 pM (NAAG) | 70000 AUc (24 h, PC3-PIP) | 50000 AUc (24 h, PC3-PIP) | 1 nmol | Qualitative; 1, 4, 24 h | Renal (24 h, kidneys 50000 AUc, liver 10000 AUc) | Data not provided | LogP = 3.00a | Data not provided | Yes | Tetrakis sulfonate Cy5.5 (897 g/mol) | λabs = 675 nm, λem = 694 nm |
| Cy5.5(SO3–)4-EuK102 | ki = 0.6 ± 0.1 nM (NAAG) | 3700 AUb (24 h, 22Rv1) | 24000 AUc (24 h, 22Rv1) | 10 nmol | Qualitative; 1, 2, 4, 24 h | Renal (24 h, kidneys 24000 AUc, liver 3540 AUc) | Data not provided | LogP = −1.36a | Data not provided | No | Tetrakis sulfonate Cy5.5 (897 g/mol) | λabs = 675 nm, λem = 694 nm |
| Cy5.5(SO3–)4-(EuK)2102 | ki = 0.1 ± 0.0 nM (NAAG) | 5000 AUb (24 h, 22Rv1) | 20000 AUc (24 h, 22Rv1) | 10 nmol | Qualitative; 1, 2, 4, 24 h | Renal (24 h, kidneys 20000 AUc, liver 0 AUc) | Data not provided. | LogP = −0.33a | Data not provided | No | Tetrakis sulfonate Cy5.5 (897 g/mol) | λabs = 675 nm, λem = 694 nm |
| Cy5.5(SO3–)4-4-(aminomethyl)benzoic acid-(EuK)2102 | ki = 0.4 ± 0.1 nM (NAAG) | 5300 AUb (24 h, 22Rv1) | 20000 AUc (24 h, 22Rv1) | 10 nmol | Qualitative; 1, 2, 4, 24 h | Renal (24 h, kidneys 20000 AUc, liver 3540 AUc) | Data not provided | LogP = 1.32ak | Data not provided | No | Tetrakis sulfonate Cy5.5 (897 g/mol) | λabs = 675 nm, λem = 694 nm |
| Cy5.5(SO3–)4-2-nitroimidazole-EuK103 | ki = 0.3 ± 0.0 nM (NAAG) | 18 AUb (24 h, 22Rv1) | 29 AUb (24 h, 22Rv1) | 10 nmol | Qualitative; 1, 2, 4, 24 h | Renal (24 h, kidneys 29 AUb, liver 15 AUb) | Data not provided | LogP = −0.31a | Data not provided | No | Tetrakis sulfonate Cy5.5 (897 g/mol) | λabs = 675 nm, λem = 694 nm |
| Cy5.5(SO3–)4-(2-nitroimidazole)2-EuK103 | ki = 3.0 ± 0.3 nM (NAAG) | 20 AUb (24 h, 22Rv1) | 46 AUb (24 h, 22Rv1) | 10 nmol | Qualitative; 1, 2, 4, 24 h | Renal (24 h, kidneys 46 AUb, liver 13 AUb) | Data not provided | LogP = −2.24a | Data not provided | No | Tetrakis sulfonate Cy5.5 (897 g/mol) | λabs = 675 nm, λem = 694 nm |
| YC-9100 | ki = 0.2 ± 0.05 nM (NAAG) | 15 AUc (24 h, PC3-PIP) | 25 AUc (24 h, PC3-PIP) | 10 nmol | Qualitative; 6 h | Renal (24 h, kidneys 25 AUc, liver 3 AUc) | Data not provided | LogP = −12.72a | Data not provided | Yes | IRDye700DX (1635 g/mol) | λabs = 689 nm, λem = 700 nm |
a
Values were calculated by using ChemAxon’s Chemicalize plugin.
b
Estimated from graph.
c
Estimated from scale bar. AU = arbitrary units.