Table 2.
Approaches to delivery of in-situ tumor-specific fluorescence for FGS
| Technique | Probe | Mechanism & clinical application | Clinical Trial | References |
|---|---|---|---|---|
|
| ||||
| Activatable probes | γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) | Fluorophore quenched by spirocyclic caging is released after proteolysis by γ –glutamyltransferase. Evaluated clinically for fluorescent in ex-vivo specimen of hepatobiliary and pancreatic cancers. | UMIN000003655 | [91,93] |
|
| ||||
| Ratiometric activatable cell penetrating peptides (RACPP’s) | Cleavable linker undergoes proteolysis by matrix metalloprotease followed by polycationic peptide linked to fluorophore uptake into cells. Evaluated clinically for FGS in breast cancers. | NCT02391194, NCT03113825 | [89,94,95] | |
|
| ||||
| Small molecule/Peptide binding | Folate-FITC | Folate conjugated with fluorescein isothiocyanate (FITC) binds to folate receptor overexpressing cells. Evaluated clinically for FGS in ovarian cancers. | EudraCT 2009-010559-29 | [96,97] |
|
| ||||
| Cyclic arginine-glycine-aspartic acid (cRGD) peptides | Peptide binds to integrins overexpressed in a number of malignancies. Evaluated clinically in immunoimaging of GI, lung, and gyn malignancies. | NCT03384511* | [98] | |
|
| ||||
| Cystiene knot peptide | Peptide binds to integrin overexpressing tumors. Evaluated clinically in immunoimaging of pancreatic cancers. | NCT02683824* | [99] | |
|
| ||||
| Urokinase-plasminogen activator (uPA) | Fragment of uPA binds to uPA receptor overexpressed in malignancies. Evaluated clinically in immunoimaging of brain, head and neck, neuroendocrine, breast, prostate, bladder, and lung cancers. | NCT02945826* | [100] | |
| NCT02965001* | ||||
| NCT03278275* | ||||
| NCT02681640* | ||||
| NCT02964988* | ||||
| NCT02805608* | ||||
| NCT02755675* | ||||
|
| ||||
| Fluorescent antibodies | Epidermal growth factor receptor (EGFR) antibodies Cetuximab, Panitumamab | Antibodies target EGFR overexpressing tumors. Evaluated clinically for FGS in head and neck, brain and pancreatic cancers. | NCT01987375 | [86,88] |
| NCT03405142 | ||||
| NCT03384238 | ||||
| NCT01987375 | ||||
| NCT02855086 | ||||
| NCT02415881 | ||||
| NCT03510208 | ||||
| NCT02736578 | ||||
|
| ||||
| Vascular endothelial growth factor receptor (VEGFR) antibodies Bevacizumab | Antibodies target VEGFR overexpressing tumors. Evaluated clinically for FGS in esophageal, breast, and pancreatic cancer. | NTR4632, NCT02743975 | [101–103] | |
| NCT02583568 | ||||
| NCT01508572 | ||||
| NCT03205501 | ||||
|
| ||||
| Carcino-embryonic antigen (CEA) antibodies | Antibodies target CEA overexpressing tumors. Evaluated clinically for FGS in colon and pancreatic cancers. | NCT02784028, NCT02973672 | [81] | |
|
| ||||
| Sialyl-Lewis antigen A also known as cancer antigen 19-1 (CA19-9) antibodies | Antibodies target CA19-9 overexpressing tumors. Evaluated clinically for immunoimaging in pancreatic cancers and other CA19-9 expressing tumors. | NCT02687230 | [82] | |
|
| ||||
| Cell surface associated mucin 1 (MUC1) antibodies | Antibodies target MUC1 overexpressing tumors. Not yet evaluated for clinical FGS. | [104,105,106] | ||
|
| ||||
| Viral reporters | OBP-401 | Selectively-replicative oncolytic adenovirus virus carrying a GFP transgene under the control of CMV promoter. Not yet evaluated for clinical FGS. | ||
|
| ||||
| NV1066 | Selectively-replicative herpes virus carrying an eGFP transgene under the control of a CMV promoter. Evaluated clinically for fluorescent detection of pancreatic cancer in peritoneal cytology. | [73–75,107] | ||