AUTHOR=Lu Xia , Zhu Meilin , Zhao Lingzhou , Qi Feiran , Zou Heng , He Peng , Zhou Haizhong , Shi Kuangyu , Du Jie 

TITLE=68Ga-labeled WVP peptide as a novel PET probe for molecular biological diagnosis of unstable thoracic aortic aneurysm and early dissection: an animal study

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1048927

DOI=10.3389/fcvm.2023.1048927

ISSN=2297-055X

ABSTRACT=<sec><title>Objective</title><p>Type IV collagen (Col-IV) is a prospective biomarker for diagnosing and treating of unstable thoracic aortic aneurysm and dissection (TAAD). This study aims to evaluate the feasibility of <sup>68</sup>Ga-labeled WVP peptide (<sup>68</sup>Ga-DOTA-WVP) as a novel Col-IV-targeted probe for TAAD biological diagnosis using PET/CT.</p></sec><sec><title>Methods</title><p>WVP peptide was modified with bifunctional chelator DOTA for <sup>68</sup>Ga radiolabeling. Immunohistochemical staining was used to evaluate the expression and location of Col-IV and elastin in aortas treated with 3-aminopropionitrile fumarate (BAPN) at different time points (0, 2, and 4 weeks). The imaging performance of <sup>68</sup>Ga-DOTA-WVP was investigated using Micro-PET/CT in a BAPN-induced TAAD mouse model. The relationship between <sup>68</sup>Ga-DOTA-WVP uptake in aortic lesions and the serum levels of TAAD-related biomarkers including D-dimer, C-reactive protein (CRP), and serum soluble suppression of tumorigenicity−2 (sST2) was also analyzed.</p></sec><sec><title>Results</title><p><sup>68</sup>Ga-DOTA-WVP was readily prepared with high radiochemical purity and stability <italic>in vitro</italic>. <sup>68</sup>Ga-DOTA-WVP Micro-PET/CT could detect Col-IV exposure of unstable aneurysms and early dissection in BAPN-induced TAAD mice, but little <sup>68</sup>Ga-DOTA-WVP uptake was shown in the control group at each imaging time point. The differences of Col-IV expression and distribution of <sup>68</sup>Ga-DOTA-WVP both in TAAD and control groups further verified the imaging efficiency of <sup>68</sup>Ga-DOTA-WVP PET/CT. Additionally, a higher sST2 level was found in the imaging positive (<italic>n</italic> = 14) than the negative (<italic>n</italic> = 8) group (9.60 ± 1.14 vs. 8.44 ± 0.52, <italic>P</italic> = 0.014).</p></sec><sec><title>Conclusion</title><p><sup>68</sup>Ga-DOTA-WVP could trace the exposure and abnormal deposition of Col-IV in enlarged and early injured aortas, showing a potential for biological diagnosis, whole-body screening, and progression monitoring of TAAD.</p></sec>