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 αvβ3-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.

RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin–RGD interactions

“…[142][143][144][145] Utilizing imaging techniques like PET or MRI in conjunction with RGD-based probes for visualizing changes in integrin expression during therapy allows early identification of responders and facilitates timely adjustments to the treatment plan if necessary. 53,[146][147][148] By employing these strategies individually or in combination, it is possible to overcome challenges posed by heterogeneous integrin expression when using | 9 of 44 RGD peptides for targeted therapies while maximizing their clinical potential. 8 | SOME AVAILABLE RGD -BASED DRUGS RGD peptides are short peptide fragments derived from the amino acid sequence of several extracellular matrix proteins, such as fibrinogen, fibronectin, vitronectin, collagen, and laminin.…”

“…RGD peptide-conjugated medicines can preferentially target angiogenesis-related integrins, resulting in more effective anti-angiogenic therapy. [43][44][45][46] RGD peptides, RGD peptide-conjugated medicines, and RGD peptide-conjugated nanoparticles/nanocarriers have considerable potential for targeted drug delivery and imaging. Their capacity to selectively target integrin-expressing cells may result in better treatment results, fewer side effects, and enhanced disease identification and monitoring.…”

“…To observe integrin expression in animal models, RGD peptides can be tagged with imaging agents like fluorescent dyes or radiotracers. [35][36][37] This can aid in identifying and monitoring illnesses caused by aberrant integrin expressions, such as 44 cancer and cardiovascular disease. Furthermore, RGD peptides can be combined with imaging agents to allow for real-time monitoring of drug distribution and treatment response.…”

Signaling Pathways and Potential Therapeutic Strategies in Cardiac Fibrosis

“…Of importance, identifying new molecular markers specific of cardiac fibrosis will enhance radio-labeled based imaging techniques as well as target the delivery of therapeutic agents toward fibrotic lesions. To date, several targets have been explored in animal models of pulmonary or myocardial fibrosis to detect selectively activated fibroblasts, MMPs, collagen, or LOX [ 103 , 105 , 106 ].…”

Recent Advances in Cardiovascular Diseases Research Using Animal Models and PET Radioisotope Tracers

“…A novel marker targeting AMOT [ 68 Ga]-sCD146 has been proposed to monitor angiogenetic progress in the regeneration of myocardial tissue [61]. The group observed a significant correlation between the increasing uptake of the [ 18 F]-FDG metabolic marker due to the recovery of residual perfusion, and the intensity of the [ 68 Ga]-sCD146 signal.…”