188Re-labelled gemcitabine/bisphosphonate (Gem/BP): a multi-functional, bone-specific agent as a potential treatment for bone metastases.
OBJECTIVE
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.
El-Mabhouh
Amal A
AA
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada T6G-2N8.
Mercer
John R
JR
D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D001842:Bone and Bones / Q000378:metabolism; D002417:Cattle; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004164:Diphosphonates / Q000493:pharmacokinetics / Q000627:therapeutic use; D017886:Durapatite / Q000378:metabolism; D012968:Etidronic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D000093542:Gemcitabine
D004164:Diphosphonates; D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D003841:Deoxycytidine; C101598:rhenium-186 HEDP; D012211:Rhenium; D017886:Durapatite; D012968:Etidronic Acid; D000093542:Gemcitabine