Radiolabelled Peptides: Optimal Candidates for Theranostic Application in Oncology

Abstract

Theranostics are drugs suitable for use in both diagnostic and therapeutic applications, and have played an important role in the advancement of modern nuclear medicine. This review explains key elements that are common to successful theranostics and highlights significant developments in the field, including our own. Specific focus is given to peptides and those features that make them most suitable for theranostic application, as well as some key radioisotopes owing to their favourable properties and high clinical utility. This report provides an overview of the techniques at the researcher’s disposal, how they have been applied to current clinically significant targets, and how they might be used and improved upon for future targets.

A Historical Review of Brain Drug Delivery

“…No imaging of the tumor was possible following the IV injection of the [ 111 In-DTPA, PEG 3400 -biotinyl]-EGF not bound to the OX26 TfRMAb [804]. Recent reviews have discussed the use of peptide radiopharmaceuticals for either therapeutic [807] or diagnostic [808] agents for brain disease. Peptides have the potential for many medical applications in the CNS as there are >100 peptide systems in the brain [801,809].…”

Synthesis of a Bifunctional Cross‐Bridged Chelating Agent, Peptide Conjugation, and Comparison of 68Ga Labeling and Complex Stability Characteristics with Established Chelators

“…NODA‐GA ((1,4,7‐triazacyclononane‐1‐glutaric acid‐4,7‐diacetic acid) is also often applied and both DOTA and NODA‐GA are used in human radiotracer applications, forming very stable complexes with [ 68 Ga]Ga 3+ [1,4] . Other options are DOTA‐GA (1,4,7,10‐tetraazacyclododececane‐1‐glutaric acid‐4,7,10‐triacetic acid) and NOTA (1,4,7‐triazacyclononane‐1,4,7‐triacetic acid), which have also shown their suitability for stable 68 Ga‐introduction and tumor PET imaging applications [2,5,6] . All complexes formed by the different chelators with [ 68 Ga]Ga 3+ differ in their charge and the number of carboxylates being not involved in complex formation (Figure 1).…”

“…68 Ga‐radiolabeled peptides have emerged as important and powerful tools for the specific and sensitive visualization of malignancies of various origin by Positron Emission Tomography (PET) in routine clinical practice. [ 1 , 2 , 3 ]…”

“…[ 1 , 4 ] Other options are DOTA‐GA (1,4,7,10‐tetraazacyclododececane‐1‐glutaric acid‐4,7,10‐triacetic acid) and NOTA (1,4,7‐triazacyclononane‐1,4,7‐triacetic acid), which have also shown their suitability for stable 68 Ga‐introduction and tumor PET imaging applications. [ 2 , 5 , 6 ] All complexes formed by the different chelators with [ 68 Ga]Ga 3+ differ in their charge and the number of carboxylates being not involved in complex formation (Figure 1 ). These two parameters can considerably influence the in vivo pharmacokinetics of the corresponding radiopeptides, as has been shown recently in several very interesting comparative studies on different chelators for 68 Ga‐peptide‐labeling, where the influence of the specific chelating agent used for [ 68 Ga]Ga 3+ introduction on the pharmacokinetic profile of the respective carrier peptide was determined.…”

“…Introduction 68 Ga-radiolabeled peptides have emerged as important and powerful tools for the specific and sensitive visualization of malignancies of various origin by Positron Emission Tomography (PET) in routine clinical practice. [1][2][3] For labeling purposes, the [ 68 Ga]Ga 3 + ion is introduced into the peptide carriers by means of complexation by a peptideconjugated chelating agent. Here, several different chelators can be employed, but the most commonly used chelating agent for 68 Ga-introduction into peptides is DOTA (1,4,7,10tetraazacyclododecane-1,4,7,10-tetraacetic acid).…”