Synthesis of Novel, Dual-Targeting 68Ga-NODAGA-LacN-E[c(RGDfK)]2 Glycopeptide as a PET Imaging Agent for Cancer Diagnosis.

Barbara Gyuricza,Dezső Szikra,Dániel Szücs,Viktória Arató,Adrienn Vágner,Judit P Szabó,Anikó Fekete

doi:10.3390/pharmaceutics13060796

Barbara Gyuricza, Dezső Szikra + Show 5 more

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https://doi.org/10.3390/pharmaceutics13060796

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Journal: Pharmaceutics	Publication Date: May 26, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: University of Debrecen

Abstract

Radiolabeled peptides possessing an Arg-Gly-Asp (RGD) motif are widely used radiopharmaceuticals for PET imaging of tumor angiogenesis due to their high affinity and selectivity to αvβ3 integrin. This receptor is overexpressed in tumor and tumor endothelial cells in the case of numerous cancer cell lines, therefore, it is an excellent biomarker for cancer diagnosis. The galectin-3 protein is also highly expressed in tumor cells and N-acetyllactosamine is a well-established ligand of this receptor. We have developed a synthetic method to prepare a lactosamine-containing radiotracer, namely 68Ga-NODAGA-LacN-E[c(RGDfK)]2, for cancer diagnosis. First, a lactosamine derivative with azido-propyl aglycone was synthetized. Then, NODAGA-NHS was attached to the amino group of this lactosamine derivative. The obtained compound was conjugated to an E[c(RGDfK)]2 peptide with a strain-promoted click reaction. We have accomplished the radiolabeling of the synthetized NODAGA-LacN-E[c(RGDfK)]2 precursor with a positron-emitting 68Ga isotope (radiochemical yield of >95%). The purification of the labeled compound with solid-phase extraction resulted in a radiochemical purity of >99%. Subsequently, the octanol–water partition coefficient (log P) of the labeled complex was determined to be −2.58. In addition, the in vitro stability of 68Ga-NODAGA-LacN-E[c(RGDfK)]2 was investigated and it was found that it was stable under the examined conditions.

Highlights

IntroductionPositron emission tomography (PET) is a non-invasive, functional imaging technique that allows the visualization of physiological and pathological processes in the human body with a high sensitivity and selectivity
The cRGDfK dimer peptide (9, E[c(RGDfK)]2 ) was chosen as vector molecule for tumor angiogenesis imaging, since the cyclic RGD analogs have shown a higher affinity to αv β3 integrin than linear peptides [25] and, in addition, the multimerization approach can lead to enhanced tumor uptake [26]
The cRGDfK dimer peptide (9, E[c(RGDfK)]2) was chosen as vector molecule for tumor angiogenesis imaging, since the cyclic RGD analogs have shown a higher affinity to αvβ3 integrin than linear peptides [25] and, in addition, the multimerization approach can lead to enhanced tumor uptake [26]

Summary

Introduction

Positron emission tomography (PET) is a non-invasive, functional imaging technique that allows the visualization of physiological and pathological processes in the human body with a high sensitivity and selectivity. This imaging method requires a radiopharmaceutical that possess a positron emitter isotope attached to the targeting molecule. This vector molecule is responsible for the delivery of the radiation to a disease site. PET is capable of diagnosing diseases, monitoring disease progression, and detecting treatment response

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Conclusion