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TRIUMF-MDS-Nordion Radiopharmaceutical R&D Collaboration

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.

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TRIUMF-MDS-Nordion Radiopharmaceutical R&D Collaboration

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  1. 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.

  2. MDSN-TRIUMF CollaborationWhy 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

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

  4. 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

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

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

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

  8. 1,3-Diaminocarbohydrate Ligands Y. Mikata et al. J. Org. Chem.2001, 66, 3783 T. Storr et al. Chem. Eur. J. 2005, 11, 195 Medicinal Inorganic Chemistry Group Medicinal Inorganic Chemistry

  9. Tripodal Glucosamine Conjugate • - 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 Medicinal Inorganic Chemistry Group Medicinal Inorganic Chemistry

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

  11. 99mTc Chemistry • Procedure for radiolabeling (TRIUMF) • 99mTc (as 99mTcO4-) added to kit containing boranocarbonate K2[H3BCO2] to produce the [99mTc(H2O)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, 3135 Medicinal Inorganic Chemistry Group Medicinal Inorganic Chemistry

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

  13. Biodistribution Ratios • 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. Medicinal Inorganic Chemistry Group Medicinal Inorganic Chemistry

  14. Thanks 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 Medicinal Inorganic Chemistry Group Medicinal Inorganic Chemistry

  15. NSERC-CRD Project Focuses on the chemistry of 68Ga and 111In 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)

  16. 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 99mTc

  17. 68Ga and 111In Chemistry • Similar Chemistry • Largely underutilized in Radiopharmaceutical field • 68Ga, t1/2=68 min from Ge generator • 111In, t1/2=67h, can be used for imaging up to a week, has 171 and 245 gammas and an Auger emission for therapy.

  18. Other Ligands

  19. New Ligands

  20. Fatty Acid Complexes

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