TRIUMF-MDS-Nordion Radiopharmaceutical R&D Collaboration TRIUMF and MDSN signed MOU Both agreed to invest $250K each into a new radiochem lab in the MHESA basement Possible matching funds from NSERC of another $250K. Expected to Grow much larger and is expected to be modeled after MDSN-Ottawa Heart Collab.

MDSN-TRIUMF Collaboration Why Now MDSN mandate for more R&D Peter Covitz as Senior VP Innovation Dennis Wester Vancouver Ops. Director of Applied Research Cara Ferreira (PhD, TRIUMF/UBC) Vancouver Ops. Applied R&D TRIUMF’s new Nuclear Medicine Division

TRIUMF/MDS-Nordion Collaboration (NSERC-CRD) Enabling Technologies for Metallic Radioisotopes in Nuclear Medicine

Team Michael Adam-PI (TRIUMF) Chris Orvig-Co-applicant (UBC Chem) Dennis Wester-Collaborator (MDSN) Cara Ferreira-Collaborator (MDSN) Eric Price (Graduate Student, May 1/09) Eszter Boros (PhD Student) Jacqueline Cawthray, PDF

Medicinal Inorganic Chemistry Group Chris Orvig and Michael J. Adam Medicinal Inorganic Chemistry Group and TRIUMF University of British Columbia Vancouver BC, Canada Carbohydrate Conjugates for SPECT Medicinal Inorganic Chemistry

Medicinal Inorganic Chemistry Group Increase availability of FDG-like imaging Generator produced isotopes Isotopes with longer half-lives Develop an FDG-like radiotherapeutic  -emitting isotopes Research Goals Medicinal Inorganic Chemistry

Medicinal Inorganic Chemistry Group FDG M = 99m Tc, 186 Re … 64 Cu, 68 Ga - an inexpensive, more available way to use the powerful tool of glucose imaging - a glucose analogue that can be used for radiotherapy FDG and PET vs.  -Emission and SPECT Medicinal Inorganic Chemistry

Medicinal Inorganic Chemistry Group Y. Mikata et al. J. Org. Chem. 2001, 66, 3783 T. Storr et al. Chem. Eur. J. 2005, 11, 195 1,3-Diaminocarbohydrate Ligands Medicinal Inorganic Chemistry

Medicinal Inorganic Chemistry Group - increasing evidence that N-functionalized glucosamines show activity with GLUT and hexokinase - recent work with ECDG has shown that molecule uses a hexosamine transporter to gain cell access (D. J. Yang et al. Radiology, 2003, 226, 465) - high yield radiolabelling - HPLC concordance - stable 24 hr. vs. 1 mM His/Cys (100x xs) T. Storr et al. Dalton Trans. 2005, 654 Tripodal Glucosamine Conjugate Medicinal Inorganic Chemistry

Medicinal Inorganic Chemistry Group Tridentate Ligands Medicinal Inorganic Chemistry N. C. Lim et al. Inorg. Chem. 2008, 47, 1337

Medicinal Inorganic Chemistry Group Procedure for radiolabeling (TRIUMF) 99m Tc (as 99m TcO 4 - ) added to kit containing boranocarbonate K 2 [H 3 BCO 2 ] to produce the [ 99m Tc(H 2 O) 3 (CO) 3 ] + precursor Excess ligand (10 -3 M) added to the kit solution to ensure complete complexation R. Alberto et al. J. Am. Chem. Soc. 2001, 123, m Tc Chemistry Medicinal Inorganic Chemistry

Medicinal Inorganic Chemistry Group the glucose analogue: T. Storr et al. Inorg. Chem. 2005, 44, 2698 Medicinal Inorganic Chemistry

Medicinal Inorganic Chemistry Group Tumour to blood ratio increases over time for the glucose and thioglucose complexes, and remains constant for the glucosamine complex. All compounds had high tumour to muscle ratios. Biodistribution Ratios Medicinal Inorganic Chemistry

Co-workers:Cheri Barta (Ph.D. 2007, UGF) Meryn Bowen Chuck Ewart (M.Sc. 2006) Cara Ferreira (Ph.D. 2006, NSERC) Dr. Neil Lim Tim Storr (Ph.D. 2005, NSERC) Funding:Natural Sciences and Engineering Research Council (Strategic) Canada Foundation for Innovation (C-HORSE) MDS Nordion TRIUMF Collaborators:Dr. Anna Celler, Medical Imaging Research group, VGH Fabio Marques, Univ. São Paulo Dr. Thomas J. Ruth, TRIUMF Profs. Shigenobu Yano and Yuji Mikata, Nara Women’s University Dr. Don Yapp, BC Cancer Agency Thanks Medicinal Inorganic Chemistry Medicinal Inorganic Chemistry Group

NSERC-CRD Project Focuses on the chemistry of 68 Ga and 111 In complexes  Ga and In have similar chemistry  The company has targeted these two radiometals as having significant potential while being largely underutilized in the radiopharmaceutical field  Funding = $600K over 3 years (NSERC-CRD)

New Bifunctional Chelators Greater stability Milder conditions for chelations Better clearance properties of complexes Higher radiochemical yields Less purification Reduce loss of In to Transferin Try to make agents to compete with 99m Tc

68 Ga and 111 In Chemistry Similar Chemistry Largely underutilized in Radiopharmaceutical field 68 Ga, t 1/2 =68 min from Ge generator 111 In, t 1/2 =67h, can be used for imaging up to a week, has 171 and 245 gammas and an Auger emission for therapy.

Other Ligands

New Ligands

Fatty Acid Complexes