Safety and Tolerability of Topotecan-Eluting Radiopaque Microspheres for Hepatic Chemoembolization in a Rabbit Preclinical Model
| Autor: | Ayele H. Negussie, Filip Banovac, J. Esparza-Trujillo, Sean L. Willis, Bradford J. Wood, Alexander Henman, Yiqing Tang, Andrew S. Mikhail, John W. Karanian, Venkatesh Krishnasamy, Ivane Bakhutashvili, Elliot Levy, Andrew L. Lewis, William F. Pritchard, Paul Wakim, David L. Woods |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Carcinoma Hepatocellular endocrine system diseases medicine.medical_treatment Urology Irinotecan Article 030218 nuclear medicine & medical imaging Microsphere 03 medical and health sciences 0302 clinical medicine Liver Neoplasms Experimental medicine Animals Humans Radiology Nuclear Medicine and imaging Embolization Alanine aminotransferase Chemoembolization Therapeutic medicine.diagnostic_test business.industry Liver Neoplasms Microspheres Tolerability Toxicity Topotecan Rabbits Topoisomerase I Inhibitors Cardiology and Cardiovascular Medicine Liver function tests business medicine.drug |
| Zdroj: | Cardiovasc Intervent Radiol |
| ISSN: | 1432-086X |
| Popis: | PURPOSE: Topotecan is a camptothecin analogue with potential advantages over irinotecan for transarterial chemoembolization (TACE) of hepatic colorectal metastases including greater anti-neoplastic activity without enzymatic activation. The purpose of this study was to assess safety and tolerability of topotecan-loaded radiopaque microspheres (ROMTOP) administered by TACE in a rabbit model, and to compare the in vitro elution of topotecan from microspheres to irinotecan. MATERIALS AND METHODS: Topotecan was loaded into radiopaque microspheres (70–150 μm, DC Bead LUMI™, Biocompatibles UK Ltd – Boston Scientific Corporation) to the maximum capacity of 80 mg/mL of microspheres. Six healthy New Zealand White rabbits underwent hepatic TACE with ROMTOP under fluoroscopic guidance until angiographic stasis. Assessment of toxicities included regular liver function tests and complete blood counts until euthanasia 28 days post TACE. In vitro topotecan elution from the microspheres was assessed using an open-loop flow-through system and compared to irinotecan. RESULTS: The mean bead volume and topotecan dose delivered were 0.086 mL (0.076–0.105 mL) and 1.99 mg/kg (1.51–2.55 mg/kg), respectively. Aspartate aminotransferase and alanine aminotransferase were elevated post-embolization but resolved within two weeks. One rabbit died two days after TACE with pyloric duodenal perforation observed at necropsy, potentially due to non-target embolization. In vitro elution of topotecan from ROMTOP was complete in 10 h compared to 3 h for irinotecan-loaded microspheres. CONCLUSION: Selective embolization with ROMTOP was tolerated at a dose of 2 mg/kg (24 mg/m(2)) in rabbits. In vitro topotecan elution from microspheres was more prolonged compared to irinotecan. |
| Databáze: | OpenAIRE |
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