Radiopharmaceuticals and the Institute for Radiochemical Engineering (IRE) John Webb, Murdoch University

Aspects of the Biophysical Behaviour of 153 Sm-EDTMP Danielle Meyrick Division of Science and Engineering, Murdoch University

Bisphosphonates (BPs)  Class of compounds characterised by a P- C-P bond or two P-C bonds.  General structure  Analogues of pyrophosphate.   Bisphosphonates 153 SmEDTMP Novel Ligands What have we learned?

 In vivo: Inhibit soft tissue calcification and bone resorption.  In vitro: Inhibit dissolution of hydroxyapatite [Ca 10 (PO 4 ) 6 (OH) 2 ] crystals.  Management of osteoporosis.  Treatment of osteolytic bone disease.  Bone targeting and chelating agents.  Inhibition of tumour invasion and tumoural bone resorption. tumoural bone resorption.  Activity is strongly dependent upon structure. Applications of Bisphosphonates Bisphosphonates 153 SmEDTMP Novel Ligands What have we learned?

Biophysical Behaviour of 153 Sm-EDTMP  Quadramet ® : 153 Sm ethylenediaminetetramethylene phosphonate (EDTMP). 153 Sm ethylenediaminetetramethylene phosphonate (EDTMP).  153 Sm is used for the palliation of bone cancer pain.  Introduced in vivo as a complex of EDTMP.  Subject of phase I/II clinical trials at RBH investigating use as a bone marrow ablation agent. Bisphosphonates 153 SmEDTMP Novel Ligands What have we learned?

Phosphonate/carboxylate compounds  Newly synthesised semi-rigid ligands. AL245 CDTMP Bisphosphonates 153 SmEDTMP Novel Ligands What have we learned?

Gamma camera image showing tissue distribution of 153 SmCDTMP six hours post injection. Good bone localisation and minimal kidney and liver accumulation is evident. Bisphosphonates 153 SmEDTMP Novel Ligands What have we learned?

Radiopharmaceuticals  Radioactivity (    + )  Metals Ga-67, Tc-99m, In-111, Re-188, Cu-64, Y-90, Sm-153, Lu-177 and others  Metal complex  M-complex conjugated to monoclonal antibody (Mab)

Radiopharmaceuticals  Diagnostic uses ( detection)  Therapeutic uses ( treatment)  Imaging technologies of increasing sensitivity and range of applications

Radiopharmaceuticals  REACTOR PRODUCED: replacement reactor under construction for the Australian Nuclear Science and Technology Organisation (ANSTO)at Lucas Heights, Sydney  HOSPITAL BASED CYCLOTRONS: new cyclotron, a WA State facility, at Sir Charles Gairdner Hospital, Perth ( short-lived positron-emitting isotopes: PET scanning)

Institute of Radiochemical Engineering (IRE)  An incorporated association (1987 Act) formed by the 4 W.A. public universities ( UWA, CUT, MU and ECU) with the Australian Nuclear Science and Technology Organisation  Launched, August 8, 2003 by Dr. Bruce Hobbs, Chief Scientist W.A.

Institute of Radiochemical Engineering (IRE)  Key goal is to gain local, national and international recognition as a leader for research into improving radiochemical outcomes  Production and assessment of new radiopharmaceuticals  Fund raising

Institute of Radiochemical Engineering (IRE)  Develop training and qualifications awarded by the 4 Universities together  Collaborative and multi- disciplinary approach  Develop strong links to Asia