TABLE 1.

Comparison between antibody and affibody as a targeting ligand

	Antibody	Affibody
Structure	Intact IgG monoclonal antibody	Small peptide chain
Size	Large size around 150 kDa	Small size around 6.5 kDa [43]
Affinity & specificity	Strong	Strong [43]
Heat stability	Poor	Stable
Manufacturing process	Difficult process	Easy process
Production	In vivo depending on the immune system	In vitro by chemical synthesis or by inexpensive bacterial production [44] (Originally IgG-binding, Z domain derived from staphylococcal surface protein A).
Cost	Costly	Not costly
Immunogenicity	The early produced murine antibodies generated human anti-mouse antibody (HAMA) response. After which the production of humanized monoclonal antibodies has been significantly decreasing the immunogenic reactions such as anaphylactic shock. However, some humanized antibodies still carry immunological risk [45]	Non-immunogenic [46]
Clearance	Long circularity time	Rapid clearance of unbound trace due to its small size [47]
Imaging properties	- Acceptable imaging contrast - Analysis few days after injection - Acceptable tumor penetration - Compatible with variable detection method.	- Strong imaging contrast - Analysis few hours after injection - Better tumor penetration due to small size and enhanced EPR effect. - Minimal background and interference. - Compatible with variable detection method [47]
Examples	- Pertuzumab: anti HER2+ antibody - Ofatumumab: anti-CD20	- ABY-035: anti-IL-17 - HEHEHE-Z08698-NOTA: anti-HER3 affibody