Table 1.

Advantages and disadvantages of targeting peptides and oligonucleotides or aptamers for PCa imaging

S. No.	Property	Peptides	Oligonucleotides or Aptamers
1.	Ease of synthesis and manufacturing	Peptide analogs are synthesized by established solid‐phase peptide synthesis (SPPS) methods, which produces reproducible constructs with accurate chemical structures. Production cost for bulk manufacturing is considerably lower than for monoclonal antibody and aptamers.133	Easy, reliable, and automated methods for synthesis of aptamers are available, which also easily facilitate chemical modifications like attachment points to tether enzymes. However, manufacturing costs are high as the technology has not yet evolved to generate large amounts within reasonable costs.134
2.	Metabolic or serum stability	Targeting peptides are generally metabolically unstable as they can be easily digested by proteases present in the blood plasma and are prone to fast renal clearance. They are also susceptible to endopeptidases and exopeptidases present in the tissues. This sometimes results in loss of bioactivity even before reaching the intended target.	Aptamers also have low metabolic stability and circulation half‐life (~2 min) due to susceptibility to nuclease degradation.
3.	Target specificity	Peptides have high affinity and specificity to a target protein as they are identified after extensive screening with a library by phage display technology.135	Aptamers also show high target specificity as they are identified by an in vitro selection process, systematic evolution of ligands by exponential enrichment (SELEX), which can be monitored to tailor affinities according to a protein target.
4.	Penetration and uptake in tumor tissues	Its small size in comparison with proteins (<50 amino acids) enables good tissue penetration and uptake in tumors.	Shows good tumor penetration due to its small size (3000‐20 000 Da), but comparably less efficient than small molecule targeting ligands.136