Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

• Published in: European journal of radiology Vol. 82; no. 12; pp. e823 - e828
• Main Authors: Dallaudière, Benjamin, Lempicki, Marta, Pesquer, Lionel, Louedec, Liliane, Preux, Pierre Marie, Meyer, Philippe, Hess, Agathe, Durieux, Marie Hèlène Moreau, Hummel, Vincent, Larbi, Ahmed, Deschamps, Lydia, Benayoun, Yohan, Journe, Clement, Perozziello, Anne, Schouman-Claeys, Elisabeth, Michel, Jean Baptiste, Serfaty, Jean Michel
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01-12-2013
• Subjects: Angiogenesis Inhibitors - administration & dosage; Animals; Anti-angiogenic; Antibodies, Monoclonal, Humanized - administration & dosage; Bevacizumab; Collagenases; Disease Models, Animal; Humans; Injections, Intralesional; Male; Pilot Projects; Radiology; Rat; Rats; Rats, Sprague-Dawley; Recovery of Function - drug effects; Tendinopathy - chemically induced; Tendinopathy - diagnostic imaging; Tendinopathy - drug therapy; Tendinosis; Tendon; Treatment Outcome; Ultrasonography, Interventional - methods; Wound Healing - drug effects; Tendinosis; Rat; Anti-angiogenic; US; Tendon
• ISSN: 0720-048X; 1872-7727
• DOI: 10.1016/j.ejrad.2013.06.012

Abstract Purpose Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity. Materials and method Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1® (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−). Results All AAT+ showed a better joint mobilization compared to PST+ at D6 ( p = 0.004) with thinner US tendon diameters ( p < 0.004), and less disorganized collagen fibers and neovessels on histology ( p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology ( p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon ( p = 0.18). Conclusion Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity.