Ophtalmic Artery Microcatheterization for Research Purposes in Pigs. A Technical Note

Requejo, Flavio; Sierre, Sergio; Marelli, Juan; Schaiquevich, Paula; Chantada, Guillermo; Asprea, Marcelo; Lipsich, José; Schumacher, Martin

doi:10.3109/08941939.2014.894599

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…Our data have some limitations related to the model used. First, the pig is a suitable animal model for performing OAC and pharmacokinetic studies due to its size that allows for feasible catheterization of the ophthalmic artery [ 16 , 21 ]. The porcine vascular anatomy has been well characterized for its intended use of this model for conducting research and in interventional radiology training [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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Topotecan Delivery to the Optic Nerve after Ophthalmic Artery Chemosurgery

et al. 2016

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Extraocular retinoblastoma is a major challenge worldwide, especially in developing countries. Current treatment involves the administration of systemic chemotherapy combined with radiation, but there is a clear need for improvement of chemotherapy bioavailability in the optic nerve. Our aim was to study the ophthalmic artery chemosurgery (OAC) local route for drug delivery assessing ocular and optic nerve exposure to chemotherapy and to compare it to exposure after intravenous infusion (IV) of the same dose in an animal model. Topotecan was used as a prototype drug that is active in retinoblastoma and based on the extensive knowledge of its pharmacokinetics in preclinical and clinical settings. Five Landrace pigs received 4mg of topotecan via OAC as performed in retinoblastoma patients. At the end of the infusion, the eyes were enucleated, the optic nerve and retina were dissected, and the vitreous and plasma were separated. After recovery and a wash-out period, the animals received a 30-min IV infusion of topotecan (4 mg). The remaining eye was enucleated and tissues and fluids were separated. All samples were stored until quantitation using HPLC. A significantly higher concentration of topotecan in the optic nerve, vitreous, and retina was obtained in eyes after OAC compared to IV infusion (p<0.05). The median (range) ratio between topotecan concentration attained after OAC to IV infusion in the optic nerve, retina and vitreous was 84(54–668), 143(49–200) and 246(56–687), respectively. However, topotecan systemic exposure after OAC and IV infusion remained comparable (p>0.05). The median optic nerve-to-plasma ratio after OAC and IV was 44 and 0.35, respectively. Topotecan OAC delivery attained an 80-fold higher concentration in the optic nerve compared to the systemic infusion of the same dose with similar plasma concentrations in a swine model. Patients with retinoblastoma extension into the optic nerve may benefit from OAC for tumor burden by increased chemotherapy bioavailability in the optic nerve without increasing systemic exposure or toxicity.

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Section: Discussionmentioning

confidence: 99%

“…In the present study we used five pigs (Landrace, Sus scrofa domestica ) weighing 25–30 kg. The animals were sedated and maintained under mechanical ventilation [ 16 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

Topotecan Delivery to the Optic Nerve after Ophthalmic Artery Chemosurgery

et al. 2016

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“…More recently, melphalan ocular pharmacology was fully characterized [64]; however, most of the studies were done after it was introduced for patient use. For IAC, the pharmacokinetic assessment of the ocular and systemic disposition of intraarterial melphalan and topotecan was carried out in nontumor-bearing swine [114] and primate [115,116] models due to the size of the animal and the size of the ophthalmic artery that technically allowed for catheterization. Despite being the best possible animal models to perform the studies on, the anatomical and physiological differences between the species only provide estimative data.…”

Section: Investigational Therapiesmentioning

confidence: 99%

Management of Retinoblastoma in Children: Current Status

Chantada

Schaiquevich

2015

Pediatr Drugs

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In recent years, there have been dramatic changes in the management of intraocular retinoblastoma. Intraocular retinoblastoma is a highly curable malignancy and current treatments are aimed to preserve vision while reducing the late effects such as treatment-induced secondary malignancies. The advent of intra-arterial chemotherapy changed the treatment paradigm from systemic treatment with chemotherapy to local treatment, and new questions emerged. While intra-arterial chemotherapy achieved encouraging results, only experience from major referral centers is reported, so its indications, advantages and risks are still to be elucidated. Many factors should be considered when choosing the appropriate conservative therapy. When the disease has extended outside the eye, the chances of cure are significantly lower and treatment should be tailored by the presence of pathology risk factors such as invasion of the choroid, the optic nerve, and the sclera. Adjuvant therapy is decided upon this information. Children with overt extraocular disease are treated with higher dose neoadjuvant therapy followed by delayed enucleation and adjuvant therapy.

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