Table 1.
Overview of therapies for colorectal cancer and potential optical molecular imaging targets for assessing their efficacy
| Drug | Molecular Targets | Putative Mechanism | Potential Molecular Imaging Targets (molecular probe) |
|---|---|---|---|
| Clinically Approved Therapies | |||
| 5-FU + leukovorin | ∙ Thymidylate synthase | ∙ Inhibition of thymidylate synthase disrupts DNA replication and repair (71) | ∙ Phosphotidylserine (labeled annexin) (101) |
| ∙ DNA and RNA | ∙ Misincorporation into DNA and RNA disrupts function (71) | ∙ Caspase-1 (activatable probe) (79) | |
| ∙ MMP-2 (activatable probe) (12) | |||
| ∙ Reduced folate receptor (labeled folic acid) (83) | |||
| Oxaliplatin | DNA | DNA alkylation causes cross-linking and induces apoptosis (80) | ∙ Phosphotidylserine (labeled annexin) (101) |
| ∙ Caspase-1 (activatable probe) (79) | |||
| Irinotecan | Topoisomerase I | Stabilization of single-stranded DNA breaks induces apoptosis (80) | ∙ Phosphotidylserine (labeled annexin) (101) |
| ∙ Caspase-1 (activatable probe) (79) | |||
| Cetuximab, panitumumab | EGFR | Monoclonal antibody against EGFR leads to tumor regression (20) | ∙ EGFR (labeled antibody) (44) |
| ∙ PI3K (labeled wortmannin) (7, 42) | |||
| ∙ Phosphotidylserine (labeled annexin) (101) | |||
| Bevacizumab | VEGF | Monoclonal antibody against VEGF leads to tumor regression (20) | ∙ VEGFR (labeled antibody) (6, 19) |
| ∙ αvβ3 (labeled targeted peptide, labeled nanoparticle) (82, 123) | |||
| ∙ VCAM-1 (64) | |||
| ∙ Vascular volume fraction (blood pool agent) (81) | |||
| ∙ uPA (activatable probe) (52) | |||
| Experimental Therapies | |||
| Celecoxib | COX-2 | Inhibition of COX-2 decreases tumor growth rates and formation of polyps (56) | ∙ MMP-2 and −9 (activatable probe) (12) |
| ∙ Phosphotidylserine (labeled annexin) (101) | |||
| Trastuzumab | HER-2/neu | Monoclonal antibody against HER-2/neu reduces tumor growth rates (73) | ∙ HER-2/neu (labeled antibody) |
| ∙ Phosphotidylserine (labeled annexin) (101) | |||
| Statins | HMG-CoA reductase | HMG-CoA reductase inhibition reduces inflammation and angiogenesis (25, 48) | ∙ Vascular volume fraction (blood pool agent) |
| ∙ MMP-2 (activatable probe) (12) | |||
| ∙ Phosphotidylserine (labeled annexin) (101) | |||
Numerous cytotoxic and molecular drugs for colorectal cancer are currently being developed and actively being used in clinical practice. This table summarizes these therapies and provides the molecular targets affected by these therapies that have already been imaged in human and/or animal studies using optical molecular imaging. COX-2, cyclooxygenase-2; EGFR, epidermal growth factor receptor; 5-FU, 5-fluorouracil; HMG-CoA, 3-hydroxy-3-methylglutaryl CoA; MMP-2, matrix metalloproteinase-2; PI3K, phosphatidylinositol 3-kinase; VEGFR, vascular endothelial growth factor receptor.