Succinate influences angiogenesis and neovascularization via a hormonelike effect on G-protein-coupled receptor 91 (GPR91). This effect has been demonstrated in the pathophysiology of diabetic retinopathy and rheumatoid arthritis. To evaluate whether succinate can play a role in acute peripheral ischemia, a preclinical study was conducted with ischemic mice treated with succinate or PBS and evaluated by imaging. Acute ischemia was followed by an increased in GPR91 expression in the ischemic muscle. As assessed with LASER-Doppler, succinate treatment resulted in an earlier and more intense reperfusion of the ischemic hindlimb compared to the control group (* p = 0.0189). A microPET study using a radiolabeled integrin ligand ([⁶⁸Ga]Ga-RGD₂) showed an earlier angiogenic activation in the succinate arm compared to control mice (* p = 0.020) with a prolonged effect. Additionally, clinical recovery following ischemia was better in the succinate group. In conclusion, succinate injection promotes earlier angiogenesis after ischemia, resulting in a more effective revascularization and subsequently a better functional recovery.

Microvesicles, so-called endothelial large extracellular vesicles (LEVs), are of great interest as biological markers and cell-free biotherapies in cardiovascular and oncologic diseases. However, their therapeutic perspectives remain limited due to the lack of reliable data regarding their systemic biodistribution after intravenous administration. Methods: Applied to a mouse model of peripheral ischemia, radiolabeled endothelial LEVs were tracked and their in vivo whole-body distribution was quantified by microSPECT/CT imaging. Hindlimb perfusion was followed by LASER Doppler and motility impairment function was evaluated up to day 28 post-ischemia. Results: Early and specific homing of LEVs to ischemic hind limbs was quantified on the day of ischemia and positively correlated with reperfusion intensity at a later stage on day 28 after ischemia, associated with an improved motility function. Conclusions: This concept is a major asset for investigating the biodistribution of LEVs issued from other cell types, including cancer, thus partly contributing to better knowledge and understanding of their fate after injection.

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.

This study aimed to develop a PET imaging agent of angiomotin (AMOT) expression, a potential biomarker of functional tissue regeneration in post-ischaemic conditions.

Many nuclear medicine departments have equipped themselves with automated dispensing systems (ADS) for PET radiopharmaceuticals, in both the operators’ and the patients’ interests. Whether partially or fully automated, to date there is no marketed ADS representing a true “closed-system”. Despite the sterile, injectable nature of ready-to-use radiopharmaceutical drug solutions manipulated by these systems, neither manufacturer’s recommendation nor literature report was found about specific qualification of the process’ sterility, or about operators’ qualification on these dispensing systems. We set up a master plan validation in a radiopharmacy equipped with Trasis Unidose®, including: 1) monthly process-simulating media-fill tests and microbiological contamination assessments of the ADS surfaces; 2) initial and periodic qualification of the operators. The microbiological qualification consisted in surface biocontamination assessment on critical zones with Tryptic-Soy agar. The operator qualification consisted in the evaluation of the operators’ knowledge and skills for using the ADS. This study highlighted a minor, handborne microbiological contamination on our first assessment, that corrective actions solved. We therefore decided to brief our operators once a month on microbiological control results, hygiene and good practices, with the support of the present case illustrating the biodecontamination efficiency. As the automation of PET monodose conditioning process still implies human intervention for material preparation and manual biodecontamination, this study illustrates that initial and periodic qualification of the environment and the conditioning process of ADS, including microbiological qualification and operators’ qualification, are needed to meet specifications.