SFI/MMI Technology Platform Workshop (3 rd June 2010)

Transcription

1 SFI/MMI Technology Platform Workshop (3 rd June 2010) How Preclinical Molecular Imaging Can Advance the Drug Development Process: Case Studies in the Oncology Domain Prof. William Gallagher Vice Principal for Research and Innovation, UCD College of Life Sciences Associate Professor of Cancer Biology, School of Biomolecular & Biomedical Science Conway Fellow, UCD Conway Institute Co Founder, OncoMark Limited

2 Brief Description of Technology Platform

3 In Vivo Imaging (of Molecular Events) Multiple imaging modalities available (optical, PET/CT, SPECT, MRI, ultrasound) Becoming an essential tool for translational research and new drug development Holds significant potential across multiple therapeutic areas (oncology, neurology, infectious disease etc.) Rapid emergence of imaging based biomarkers van der Meel R et al. Drug Discovery Today (2010)

4 Multi Modality Molecular Imaging Platform: Current Infrastructure in Place Optical Imaging Intravital Imaging SOPF/Xenograft Facilities Ultrasound Imaging PET/CT and SPECT/CT Imaging Suite

5 IVIS Spectrum (Caliper Life Sciences) Imaging of novel fluorophore in nude mouse, of 10mg/kg compound I.V (10min post-injection) MDA-MB-231 GFP (SQ xenograft) Bioluminescent imaging Fluorescent imaging Partial 3D tomographic capabilities HeLa-Luc (SQ xenograft).after 150mg/kg luciferin substrate. I.P.)

6 Radionuclide Imaging (GE Healthcare Systems) Explore SpecZT CT120 Triumph PET/CT (LabPet 4, X O CT) 1 st Scans Planned for Q2 2010

7 Molecular Imaging Suite

8 In Vivo Imaging: Preclinical Evaluation & Bridge to Clinical Translation Drug Efficacy [Optical Imaging] Optical Imaging Can Provide Rapid, Facile Measurements Radionuclide Imaging Provides Clear Bridge to Clinical Translation 10 Days Posttreatment Pre Treatment 4h posttreatment MDA MB 231 Luc 24h posttreatment 48h posttreatment >2.0 million Euro in Infrastructural Support from SFI/UCD Positron Emission Tomography [18F FDG] Control tumour Treated tumour Radionuclide Imaging Reagents Supported by Erigal Pre treatment 30min post PDT 24h post PDT 48h post PDT Rat mammary tumours (MAT B III) Byrne AT et al. Brit J Cancer (2009) 3Rs [Replacement, Reduction Refinement]

9 What is the Platform Trying to Achieve? Provide cutting edge in vivo imaging platform to: Examine key pathophysiological events, particularly in cancer and inflammatory disease areas Evaluate drug efficacy in these therapeutic domains Input into ongoing development of novel imaging agents (optical, radionuclide)

10 Access Principles Currently accessed via a collaborative model, given requirement for on site animal model work Open to all researchers, both academic and industrial Staff supports available for in vivo work, albeit some part financing will be required Contact point: emer.conroy@ucd.ie Considering move to service based function in the medium term (via OncoMark)

11 How does the Platform fit into the Innovation and Commercialisation Agenda? Assist academic and industrial groups, particularly SMEs, in further validation of therapeutic target/agents at the preclinical level Particularly in respect to adding value to core intellectual property Facilitate collaborative engagement with large pharma/biotech partners to advance drug development pipelines (e.g. MTCI) Provide expanded opportunities for spin off in respect to provision of service based activities

12 Case Studies in the Oncology Domain

13 Rapid Clearance In Vivo of ADMP06: A Novel Photosensitising Agent SFI RFP ( ) Pre-treatment 15 min post-pdt 24 hr post-pdt Byrne AT et al. (2009). A multi modality molecular imaging approach to therapeutic assessment. British Journal of Cancer, 101(9), Issued US Pat. 7,220,732 B2 Patent pending in the EU

14 Bioluminescence Imaging Showing Efficacy of PDT with ADPM06 Pre-treatment 6 hr post-pdt 96 hr post-pdt MDA MB 231 Luciferase cells injected SQ (5 x 10 6 ); 10 days post SQ, animals treated with 2mg/kg ADPM J/cm 2 light Animals injected with 150mg/kg Luciferin intraperitonally (I.P.) Images acquired using IVIS min post injection

15 Bolus PET and MRI Following PDT with ADPM06 Control tumour Treated tumour Pre-treatment 30 min post-pdt 24 hr post-pdt 48 hr post-pdt Control Treated tumour tumour 3 hrs post -PDT 24 hr post-pdt 48 hr post-pdt

16 SFI Strategic Research Cluster Molecular Therapeutics for Cancer Industry partners Amgen, GSK, Pfizer, Merck, Roche, Novartis AntiCancer Inc, Caliper, Erigal 5.6 million euro/5 yrs (plus overhead) Monitoring response to therapy Target Identification Molecularly Targeted Agents In Vitro Evaluation In Vivo Evaluation Translational Clinical Trials Lead PI: Prof. John Crown Co PIs: Prof. Joe Duffy Prof. William Gallagher Prof. William Watson Dr. Judith Harmey Resistance to targeted therapies Collaboration between DCU, UCD/St. Vincent s Hospital, RCSI, TCD/St. James s Hospital

17 Monitoring Novel Drug Combinations in Xenograft Models of Breast Cancer (e.g. MAbs and small molecule inhibitors) BT474 GFP (HER2+) Fluorescent Model Vehicle Drug A Drug B Drug C A + C B + C O Donovan, N. et al. (2010). Synergistic interaction between trastuzumab and EGFR/HER 2 tyrosine kinase inhibitors in HER 2 positive breast cancer cells. Investigational New Drugs, in press.

18 Evaluation of Novel Anti Cancer Therapeutics Toxicity studies within Mesothelioma Model Prof. Clive Williams (TCD) Validation of new imageable in vivo mesothelioma model Efficacy study response to novel anti cancer therapeutics Bioluminescent Imaging Showing Validation of In Vivo Mesothelioma Model 24 hrs 48 hrs 7 days 15 days 36 days

19 GE Healthcare Collaboration Supporting pre clinical PET and SPECT imaging in UCD (basic and advanced training) Facilitate academic outreach to other centres of excellence in radionuclide imaging UCD to become potential validation partner for novel tracers (e.g. imaging angiogenesis), particularly in respect to advancing drug development studies

20 Erigal/M2i & Blackrock Clinic Support Erigal Ltd. specialises in the provision of radiopharmaceuticals for clinical diagnostic use Has agreed to kick start the facility via the provision of the most widely employed PET radiotracer, 18 F FDG, on a no cost basis (for 1 2 year period) Blackrock Clinic providing initial supply of Tc 99m (for SPECT studies)

21 Spin out from UCD Founded in May 2007 (full implentation in 2009) Offices in NovaUCD; licence to use technologies in UCD Conway Institute Focus: Development and application of novel biomarker panels, and associated technologies, on both tissue and biological fluids Collaborative activities: FP7 Funding (Target Melanoma, AngioTox, RATHER) Services: Digital slide scanning Tissue microarray construction Automated image analysis Consultancy/EU project management Product development: Novel image analysis toolkit for quantitating biomarker expression in tissues assessed by immunohistochemistry Opportunity to Expand out Services to Include Preclinical Evaluation Combined with Advanced In Vivo Imaging

22 Acknowledgements Co applicants for SFI Equipment Grants 2006 and 2007 UCD Emer Conroy Liam Shiels Aisling O Connor Agnieszka Zagozdzon Prof. Donal O Shea Dr. Kathleen Curran Dr. Luis Leon Dr. Annette Byrne (RCSI) University of Sherbrooke Kim Mongrain Prof. Roger Lecomte Dr. Jacques Rousseau Dr. Martin Lepage Dr. Luc Tremblay Erigal/M2i/Blackrock Clinic Dr. George Duffy Dr. Ruairi O Donnell Dr. Ciaran Boylan GE Healthcare