Amal A El-Mabhouh1, John R Mercer. 1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada T6G-2N8.
Abstract
PURPOSE: This study investigated the bone-binding affinity and biodistribution of a (188)Re-labelled gemcitabine/bisphosphonate (Gem/BP) conjugate, a multi-functional drug designed to deliver tumour-specific combined radiotherapy and chemotherapy to the bone using the high bone-binding affinity of the bisphosphonate group. METHODS: The Gem/BP conjugate was labelled at high radiochemical purity with (188)Re. The bone-binding affinity of the (188)Re-Gem/BP was studied in vitro in purified hydroxyapatite emulsion and powdered bovine bone. In vivo biodistribution studies were carried out in normal BALB/c mice. RESULTS: (188)Re-Gem/BP demonstrated strong and stable binding in both in vitro systems. In vivo (188)Re-Gem/BP showed bone uptake, rapid blood clearance and rapid elimination of unbound activity. The bone tissue demonstrated the highest concentration of bound radioactivity exempting the kidneys. Approximately 67% of retained whole-body activity was bound to the bone at 8 h after (188)Re-Gem/BP administration. CONCLUSIONS: (188)Re-Gem/BP demonstrated high, selective and persistent bone binding and can be considered as a model compound for multi-functional bone-specific therapy for bone metastases.
PURPOSE: This study investigated the bone-binding affinity and biodistribution of a (188)Re-labelled gemcitabine/bisphosphonate (Gem/BP) conjugate, a multi-functional drug designed to deliver tumour-specific combined radiotherapy and chemotherapy to the bone using the high bone-binding affinity of the bisphosphonate group. METHODS: The Gem/BP conjugate was labelled at high radiochemical purity with (188)Re. The bone-binding affinity of the (188)Re-Gem/BP was studied in vitro in purified hydroxyapatite emulsion and powdered bovine bone. In vivo biodistribution studies were carried out in normal BALB/c mice. RESULTS: (188)Re-Gem/BP demonstrated strong and stable binding in both in vitro systems. In vivo (188)Re-Gem/BP showed bone uptake, rapid blood clearance and rapid elimination of unbound activity. The bone tissue demonstrated the highest concentration of bound radioactivity exempting the kidneys. Approximately 67% of retained whole-body activity was bound to the bone at 8 h after (188)Re-Gem/BP administration. CONCLUSIONS: (188)Re-Gem/BP demonstrated high, selective and persistent bone binding and can be considered as a model compound for multi-functional bone-specific therapy for bone metastases.
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