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Comparison of a New ⁶⁸Ga-Radiolabelled PET Imaging Agent sCD146 and RGD Peptide for In Vivo Evaluation of Angiogenesis in Mouse Model of Myocardial Infarction.

ABSTRACT: Ischemic vascular diseases are associated with elevated tissue expression of angiomotin (AMOT), a promising molecular target for PET imaging. On that basis, we developed an AMOT-targeting radiotracer, ⁶⁸Ga-sCD146 and performed the first in vivo evaluation on a myocardial infarction mice model and then, compared AMOT expression and α_vβ₃-integrin expression with ⁶⁸Ga-sCD146 and ⁶⁸Ga-RGD₂ imaging. After myocardial infarction (MI) induced by permanent ligation of the left anterior descending coronary artery, myocardial perfusion was evaluated by Doppler ultrasound and by ¹⁸F-FDG PET imaging. ⁶⁸Ga-sCD146 and ⁶⁸Ga-RGD₂ PET imaging were performed. In myocardial infarction model, heart-to-muscle ratio of ⁶⁸Ga-sCD146 imaging showed a significantly higher radiotracer uptake in the infarcted area of MI animals than in sham (* p = 0.04). Interestingly, we also observed significant correlations between ⁶⁸Ga-sCD146 imaging and delayed residual perfusion assessed by ¹⁸F-FDG (* p = 0.04), with lowest tissue fibrosis assessed by histological staining (* p = 0.04) and with functional recovery assessed by ultrasound imaging (** p = 0.01). ⁶⁸Ga-sCD146 demonstrated an increase in AMOT expression after MI. Altogether, significant correlations of early post-ischemic ⁶⁸Ga-sCD146 uptake with late heart perfusion, lower tissue fibrosis and better functional recovery, make ⁶⁸Ga-sCD146 a promising radiotracer for tissue angiogenesis assessment after MI.

SUBMITTER: Moyon A

PROVIDER: S-EPMC8466330 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Tracers triggering ?v?3 integrins, such as certain RGD-containing peptides, were found promising in previous pilot studies characterizing high-grade gliomas. However, only limited comparisons have been performed with current PET tracers. This study aimed at comparing the biodistribution of 18F-fluorodeoxyglucose (18F-FDG) with that of 68Ga-NODAGA-RGD, an easily synthesized monomeric RGD compound with rapid kinetics, in two different rodent models of engrafted human glioblastoma.Nude rodents bearing human U87-MG glioblastoma tumor xenografts in the flank (34 tumors in mice) or in the brain (5 tumors in rats) were analyzed. Kinetics of 68Ga-NODAGA-RGD and of 18F-FDG were compared with PET imaging in the same animals, along with additional autohistoradiographic analyses and blocking tests for 68Ga-NODAGA-RGD.Both tracers showed a primary renal route of clearance, although with faster clearance for 68Ga-NODAGA-RGD resulting in higher activities in the kidneys and bladder. The tumor activity from 68Ga-NODAGA-RGD, likely corresponding to true integrin binding (i.e., suppressed by co-injection of a saturating excess of unlabeled RGD), was found relatively high, but only at the 2nd hour following injection, corresponding on average to 53% of total tumor activity. Tumor uptake of 68Ga-NODAGA-RGD decreased progressively with time, contrary to that of 18F-FDG, although 68Ga-NODAGA-RGD exhibited 3.4 and 3.7-fold higher tumor-to-normal brain ratios on average compared to 18F-FDG in mice and rat models, respectively. Finally, ex-vivo analyses revealed that the tumor areas with high 68Ga-NODAGA-RGD uptake also exhibited the highest rates of cell proliferation and ?v integrin expression, irrespective of cell density.68Ga-NODAGA-RGD has a high potential for PET imaging of glioblastomas, especially for areas with high integrin expression and cell proliferation, although PET recording needs to be delayed until the 2nd hour following injection in order to provide sufficiently high integrin specificity.

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Comparison of a New 68Ga-Radiolabelled PET Imaging Agent sCD146 and RGD Peptide for In Vivo Evaluation of Angiogenesis in Mouse Model of Myocardial Infarction.

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Comparison of a New ⁶⁸Ga-Radiolabelled PET Imaging Agent sCD146 and RGD Peptide for In Vivo Evaluation of Angiogenesis in Mouse Model of Myocardial Infarction.