An Optimized Integrin α6-Targeted Magnetic Resonance Probe for Molecular Imaging of Hepatocellular Carcinoma in Mice

Abstract

Introduction: Integrin α6 is an attractive diagnostic biomarker for molecular imaging of hepatocellular carcinoma (HCC) as it has an extremely high positive rate (approximately 94%) in clinical early-stage HCC. In this study, based on our previously identified integrin α6-targeted peptide, we developed an optimized integrin α6-targeted magnetic resonance (MR) probe dubbed DOTA(Gd)-ANADYWR for MR imaging of HCC in mice. Materials and Methods: The longitudinal (R 1 ) relaxivity of DOTA(Gd)-ANADYWR was measured on a 3.0 T MR system . The specific tumor enhancement of the agent was investigated in four distinct mouse models, including subcutaneous, orthotopic, genetically engineered and chemically induced HCC mice. Results: The R 1 relaxivity value of DOTA(Gd)-ANADYWR is 5.11 mM −1 s −1 at 3.0 T, which is similar to that of the nonspecific clinical agent Gadoteridol. DOTA(Gd)-ANADYWR generated superior enhanced MR signal in HCC lesions and provided complementary enhancement MR signals to the clinically available hepatobiliary MR contrast agent gadoxetate disodium (Gd-EOB-DTPA). Importantly, DOTA(Gd)-ANADYWR could efficiently visualize small HCC lesion (approximately 1 mm) which was hardly detected by the clinical Gd-EOB-DTPA. Conclusion:These findings suggest the potential application of this integrin α6-targeted MR probe for the detection of HCC, particularly for small HCC.

Identification of an IGF2BP2-Targeted Peptide for Near-Infrared Imaging of Esophageal Squamous Cell Carcinoma

“…With the development of molecular biology, the diagnosis and treatment of tumors has been transformed from the traditional macroscopic level to another battlefield tailored to tumor microscopic molecules, which undoubtedly provides tremendous prospects for our screened peptide to make a grand entrance in ESCC diagnosis and treatment. The property of peptides to easily couple with other chelating groups allows them to be readily designed as agents for other imaging modalities, such as positron emission computed tomography (PET) imaging [ 24 ] or magnetic resonance imaging (MRI) [ 26 ]. Considering that IGF2BP2 is expressed in the cytoplasm, we conjugated an arginine-penetrating amino acid sequence to the peptide, which will endow the peptide with the potential to reach the interior of the cell.…”

Integrin α6 targeted cancer imaging and therapy

“…In addition, integrin a6 was present abundantly in lung-tropic exosomes and mediate exosomes homing to the lung [47]. The abnormally high expression of integrin a6 has been correlated with cancer progression and poor prognosis of multiple tumor types [48]. This resulted in integrin a6 being an attractive target for cancer imaging and therapy.…”

“…The S5 peptide with higher affinity provides a critical raw material for the development of the second-generation integrin a6-targeted MR probe. The optimized integrin a6-targeted peptide S5 was further conjugated with Gd(III) chelates to develop integrin a6-targeted MR contrast agent DOTA(Gd)-ANADYWR (abbreviated as Gd-S5) [48]. The chemical structure of Gd-S5 is shown in Figure 2B.…”

Integrin α6-Targeted Molecular Imaging of Central Nervous System Leukemia in Mice

“…We further translated the RWY peptide into an integrin α6-targeted PET probe and MRI probe that have been successfully applied for tumor imaging of the integrin α6 expression ( Feng GK et al, 2019 ; Xiao et al, 2019 ; Zhang Y et al, 2020 ; Gao et al, 2020 ). Recently, our group improved the characteristics of the peptide by alanine scanning and obtained a novel integrin α6-targeting peptide CRWYDANAC (dubbed S5) which exhibited a higher specificity and affinity to integrin α6 ( Mei et al, 2020 ; Lin et al, 2021 ). On these bases, we further developed the targeted molecular imaging probes for near-infrared fluorescence (NIRF) imaging, MRI, and PET based on the S5 peptide, which is called Cy5-S5, Gd-S5, and 18 F-S5 in short.…”