TABLE 2.

Summary of Potential Targets Molecular Imaging Purposes for PDAC With Main Advantages and Disadvantages

Target	Type	Localization	Main Advantage	Main Disadvantage	References
ALCAM (CD166)	Glycoprotein in immunoglobulin family	Cell membrane	Expression in PDAC 2.5x higher compared to normal pancreatic tissue.	Expression on activated immune cells and the expression of ALCAM in pancreatitis is unknown.	^100,101
α_vβ₆	Integrin	Cell membrane	Diffuse, strong expression in PDAC.	Mild expression on normal ductal tissue.	^75,150
CA 19-9	Glycosylation product presented on cell surface proteins	Cell membrane	Expressed in up to 90% of all pancreatic cancers.	Expression on pancreatitis and normal ductal tissue.	^87,88,90,151
Cath E	Proteolytic enzyme	Intracellular	Ideal for imaging purposes due to potential use of activatable probes and differentiation between PDAC, normal pancreatic tissue, and pancreatitis.	Intracellular location of target makes internalization of probe required.	^53,115,152
Claudin 4	Integral membrane protein	Tight junctions	Upregulation in metastasis and expression in PanIN 3.	Ability to discriminate between PDAC and pancreatitis is unknown. Overexpression in PanIN 1 and 2.	^58,153
EGFR	Receptor tyrosine kinase	Cell membrane	EGFR-mediated cellular internalization of targeted particles.	EGFR is expressed in pancreatitis and on duodenal tissue, which could potentially interfere with the surgical field.	^75,81,154
Endoglin (CD105)	Type 1 membrane glycoprotein	Cell membrane	Expression levels vary throughout tumor growth, and overexpression is related to poor prognosis.	Expression is restricted to vascular endothelial cells undergoing active angiogenesis. Expression in pancreatitis is unknown.	^77,155
Mesothelin	GPI-anchored glycoprotein	Cell membrane	Expressed in PDAC and not in normal pancreatic tissue or in pancreatitis.	Mesothelin is released into the bloodstream what could reduce the signal at tumor site.	^156,157
Mucin-1	O-glycosylated proteins	Cell membrane	Expression on apical surface in normal tissue. Expression is correlated with more aggressive biological behavior.	Possible downregulation of expression after neoadjuvant therapy. Present in the RNA of pancreatitis patients.	^85,158,159
NGAL	Secreted protein	Extracellular	Potential biomarker for early detection, can also differentiate between PDAC and pancreatitis in urine and bile.	Not bound on tumor cell membrane, which could complicate imaging specificity.	^160,161
PCSA	GPI-anchored glycoprotein	Cell membrane	Upregulation in PDAC compared to pancreatitis and normal pancreatic tissue.	Overexpressed in only 60% of pancreatic cancers.	^56,162
Plectin-1	Protein for linkage in cytoskeleton	Cytoplasm	Overexpressed in PDAC compared to normal pancreatic tissue and pancreatitis. Also expressed in PanIN 3 and is therefore a potential marker for early detection.	Target is expressed in the cytoplasm as opposed to on the cell membrane.	⁸²
TF	Glycoprotein	Cell membrane	TF is used in staging and is correlated with incidence of metastases and with overall survival.	The expression of TF in pancreatitis in humans in unknown.	^98,163
TfR	Glycoprotein	Cell membrane	Upregulation is induced by hypoxia, a known feature of PDAC.	Receptors are highly expressed in the liver. Expression of TfR in pancreatitis is unknown.	^102,103,164
Thy1	GPI-anchored glycoprotein	Cell membrane	Marker for cancer-associated fibroblasts; also expressed on tumor vasculature but not in pancreatitis.	Thy1 is present on stromal cells, which is also upregulated in pancreatitis.	^79,165
uPAR	GPI-anchored glycoprotein	Cell membrane	Expression on both tumor cells and stromal cells in the tumor microenvironment.	High uPAR staining in negative lymph nodes due to staining of tumor microenvironment.	^75,166,167
VEGFR2	Receptor tyrosine kinase	Cell membrane	Upregulated in 72% of all PDAC cases.	Restricted to vascular endothelium. VEGFR2 expression is increased in pancreatitis.	^{75,154,168,169}