Background: Cancer is the leading cause of death worldwide. Early detection can reduce the disadvantageous
effects of diseases and the mortality in cancer. Nuclear medicine is a powerful tool that has the ability
to diagnose malignancy without harming normal tissues. In recent years, radiolabeled peptides have been
investigated as potent agents for cancer detection. Therefore, it is necessary to modify radiopeptides in order to
achieve more effective agents.
Objective: This review describes modifications in the structure of radioconjugates with spacers who have improved
the specificity and sensitivity of the peptides that are used in oncologic diagnosis and therapy.
Methods: To improve the biological activity, researchers have conjugated these peptide analogs to different
spacers and bifunctional chelators. Many spacers of different kinds, such as hydrocarbon chain, amino acid
sequence, and poly (ethyleneglycol) were introduced in order to modify the pharmacokinetic properties of these
Results: Different spacers have been applied to develop radiolabeled peptides as potential tracers in nuclear
medicine. Spacers with different charge and hydrophilicity affect the characteristics of peptide conjugate. For
example, the complex with uncharged and hydrophobic spacers leads to increased liver uptake, while the composition
with positively charged spacers results in high kidney retention. Therefore, the pharmacokinetics of
radio complexes correlates to the structure and total charge of the conjugates.
Conclusion: Radio imaging technology has been successfully applied to detect a tumor in the earliest stage. For
this purpose, the assessment of useful agents to diagnose the lesion is necessary. Developing peptide radiopharmaceuticals
using spacers can improve in vitro and in vivo behavior of radiotracers leading to better noninvasive
detection and monitoring of tumor growth.