The Influence of Different Spacers on Biological Profile of Peptide Radiopharmaceuticals for Diagnosis and Therapy of Human Cancers

Abstract

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 biomolecules. 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.

Preparation and evaluation of 99mTc‐HYNIC‐D(TPPE) as a new targeted imaging probe for detection of colon cancer: Preclinical comparison with 99mTc‐HYNIC‐EPPT

“…Direct labeling is a simple procedure, but some drawbacks regarding lack of specificity and poor in vivo stability have limited its applicability, whereas indirect labeling with bifunctional chelating agents overcomes these difficulties in the preparation of the 99m Tc‐labeled peptides (Rezazadeh & Sadeghzadeh, 2019). Since adding a chelating moiety and a radionuclide may affect receptor‐binding affinity of the peptide, a spacer is used to keep the chelator away from the bioactive domain (Farahani, Maleki, & Sadeghzadeh, 2019). In 2004, Okarvi examined a N 3 S chelate system for labeling an analog of αM2 peptide with 99m Tc through a triproline (Pro 3 ) residue as a spacer for detection of breast carcinoma.…”