Molecular Imaging and Radionuclide Therapy Research in Oncology
Francois Benard, MD, FRCPC Professor, Department of Radiology BC Leadership Chair in Functional Cancer imaging University of British Columbia Vice President Research, BC Cancer Construction of a new facility 2009-10 Infrastructure
• Medical cyclotron • 12 hot cells for radiochemistry • Medicinal chemistry laboratory • Radiopharmacology laboratory • Good manufacturing practice compliant radiopharmacy • Preclinical imaging (SPECT/CT, PET/CT, optical. US) • Clinical imaging (2 x PET/CT) • Quality Assurance Program Pre-clinical and Clinical Molecular Imaging
PET/CT SPECT/CT
1.3 mm 0.4 mm
10-15 mm
4.5 mm
(at Vancouver General Hospital) Microscopic radionuclide imaging
177Lu-CCZ01118 177Lu-CCZ01118 100% 1 hour p.i. 24 hour p.i.
50%
6 mm
0% Clinical Program
• Currently 37 patient studies per day on 2 scanners • From 8 am to 10 pm, 6 days a week • Over 72,600 studies performed to date • Multiple clinical trials, notably: • 18F-FDG in lymphoma and numerous clinical trials • 18F-DCFPyL in recurrent prostate cancer • 11C-methionine in parathyroid adenomas (complete) • 18F-Fluorodeoxygalactose for hepatocellular carcinoma • 68Ga-DOTA-TOC for neuroendocrine tumours • 18F-DOPA for neuroendocrine tumours • 177Lu-PSMA and 177Lu-DOTATOC therapy trials starting late 2018/early 2019 Clinical Trials
Baseline Post Tx
Cyclotron vs Generator 99mTc FDG 99mTc Bone Scan Na18F PET Scan
Glucose
FES Hypoxia Neuroendocrine tumour imaging
• Difficult to localize by conventional imaging or regular PET/CT scans
Regular 18F-FDG PET scan 68Ga-DOTATOC PET scan Prostate Cancer Imaging Key Collaborative Achievements
• Development of cyclotron production of 99mTc
Production Method A Production Method B 11 Key Collaborative Achievements
• Liquid Target Implementation
ZR-75-1 xenografts
68Ga-gen 68Ga-cyclo
89Zr solid vs liquid targets 68Ga generator vs liquid targets Radiopharmaceutical Development
h t l s
24 hr 48 hr 72 hr 5 days 7 days
CA-IX Radiolabeled antibodies
! ! ! Melanoma Breast and Breast and Imaging + Therapy neuroblastoma Prostate
! 68Ga-sulfonamide CA-IX imaging 5 Year Overview
• Novel Radiopharmaceutical Development for diagnosis and therapy 18 • F-BF3 technology to clinical trials • Receptor imaging • Protease imaging • Monoclonal antibodies • Accelerate the translation of radioligand/targeted alpha therapy towards routine clinical use via clinical trials • Expand research in dosimetry (and microdosimetry) of radioligand therapy • Explore combinations of novel diagnostic/therapeutic isotope pairs to advance personalized cancer therapy Novel Radiopharmaceutical Development
18 • Advance F-BF3 technology to clinical trials • Neuroendocrine tumours (AMBF3-TATE) • Prostate cancer imaging (PSMA) • Advance bradykinin receptor imaging to clinical trials • Melanoma imaging and therapy • Novel stabilized MC1R derivatives (68Ga,18F, 225Ac and 177Lu) • Improved radiopharmaceuticals for established targets • CXCR4, GRPR, VLA-4, PSMA • Novel radiotracers targeting proteases • Matriptase • MMP2 and MMP9 • Novel radiolabeled antibodies • Pancreatic and ovarian cancers 18F-octreotide derivatives
18 18 18 F-AmBF3-TATE F-AmBF3-TOC F-AmBF3-JR11 68Ga-Bradykinin Receptor Imaging P04158 (B9858) Z02090 (B9958)
Pos PEG2 NODA-Pos DOTA-PEG2 18F-labeled MSH derivatives
BF3-Pip-Nle-CycMSHhex New PSMA targeting radiopharmaceuticals
2h post inj. 2h post inj. 2h post inj. 4h post inj. 2h post inj. 0-5% id/g 0-5% id/g 0-5% id/g 0-20% id/g 0-15% id/g
DCFPyL HTK1069 HTK1070 Albumin HTK01174 Binder Radioligand Therapy Research
223 • Established RaCl2 therapy • New program in Neuroendocrine Tumours • Imaging program has started • Validation batches underway for 177Lu – start date early 2019 • New $4.5M Prostate Cancer Canada/Movember grant for multicentre study on prostate cancer therapy • Randomized comparison with docetaxel • Start date early 2019 • Participation in Endocyte Phase III trial • Site initiation visit December 2018 • New funding for investigator-initiated prostate cancer clinical trials • Personalized dose-adjusted prostate cancer therapy • Phase 1/2 study of 225Ac-PSMA therapy Novel albumin binder PSMA-ligands The next frontier: Rare Isotopes for Cancer Therapy
• Newly funded $9.8M addition to TRIUMF’s Advanced Rare Isotope Laboratory (ARIEL) Functional Imaging Investigators
• Radiochemistry: Kuo-Shyan Lin, PhD • Medical Physics: Arman Rahmim, PhD • Clinical: Don Wilson, MD Kim Chi, MD Jonathan Loree, MD • Translational/Clinical: François Bénard, MD • Key collaborators (UBC/SFU/TRIUMF): David Perrin, PhD (UBC) Chris Orvig, PhD (UBC Paul Schaffer, PhD (TRIUMF) Rob Britton, PhD (SFU) • Research Associates and post-docs • Chengcheng Zhang, PhD (biochemistry and molecular pharmacology) • Zhengxing Zhang, PhD (radiochemistry) • Julie Rousseau, PhD (radiolabeled antibodies and biology) • Hsiou-Ting Kuo, PhD (radiochemistry) • Joseph Lau, PhD (molecular biology and pharmacology, now at NIH) • Carlos Uribe, PhD (medical physics) • Jason Crawford, PhD (medical physics) • Aron Roxin (radiochemistry) Students and Technical Staff
• Daniel Kwon (MD/PhD candidate) • Milena Colovic (PhD candidate) • Ivica Bratanovic (MSc candidate) • Theresa Law (MSc candidate) • Etienne Rousseau, MD (fellow) • Marin Simunic (MSc candidate) • Helen Merkens (lab manager) • Jutta Zeisler (molecular biology) • Nadine Colpo (preclinical imaging) • Navjit Hundal (preclinical imaging) • Katrin Gitschtaler (animal technician) • Guillaume Langlois (radiochemistry technician) • Jinhe Pan (radiochemistry technician) • Hayley Corbett and Iulia Dude, clinical research manager and coordinator • Clinical staff (7 physicians and 58 other staff for cyclotron, radiochemistry and clinical scanning)