Abstract
Angiogenesis has a pivotal role in tumor growth and the metastatic process. Molecular imaging was shown to be useful for imaging of tumor-induced angiogenesis. A great variety of radiolabeled peptides have been developed to target αvβ3 integrin, a target structure involved in the tumor-induced angiogenic process. The presented study aimed to synthesize deferoxamine (DFO)-based c(RGD) peptide conjugate for radiolabeling with gallium-68 and perform its basic preclinical characterization including testing of its tumor-imaging potential. DFO-c(RGDyK) was labeled with gallium-68 with high radiochemical purity. In vitro characterization including stability, partition coefficient, protein binding determination, tumor cell uptake assays, and ex vivo biodistribution as well as PET/CT imaging was performed. [68Ga]Ga-DFO-c(RGDyK) showed hydrophilic properties, high stability in PBS and human serum, and specific uptake in U-87 MG and M21 tumor cell lines in vitro and in vivo. We have shown here that [68Ga]Ga-DFO-c(RGDyK) can be used for αvβ3 integrin targeting, allowing imaging of tumor-induced angiogenesis by positron emission tomography.
Highlights
Over the last 30 years, many radiolabeled peptides have been evaluated as promising radiotracers for imaging tumors by means of positron emission tomography (PET) or single photon emission computerized tomography (SPECT) [1,2]
To improve the pharmacokinetic profile, especially in vivo stability against enzymatic cleavage of RGD peptides alongside maintenance of high activity and specificity for αvβ3 integrin, several approaches have been developed in the past [18]
We have developed synthetic protocols for simple preparation of RGD peptides conjugated with deferoxamine
Summary
Over the last 30 years, many radiolabeled peptides have been evaluated as promising radiotracers for imaging tumors by means of positron emission tomography (PET) or single photon emission computerized tomography (SPECT) [1,2]. The biological effects of such peptides are mediated via the high affinity targeting of specific receptors. These receptors are often massively overexpressed in numerous cancers, compared to their relatively low density in physiological organs, which is the main principle allowing molecular imaging and therapy of tumors with radiopeptides [3]. Integrins are heterodimeric transmembrane receptors interacting with a diverse groups of extracellular ligands [5] They regulate cellular growth, proliferation, migration, signaling, and cytokine activation and release and thereby play important roles in cell proliferation and migration, apoptosis, tissue repair, as well as in all processes critical to inflammation, infection, and angiogenesis [6]. A large variety of radiotracers based on RGD peptides have been developed and tested for targeting αvβ integrin in both preclinical and clinical settings
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