Arutselvan Natarajan1, Shyam M. Srinivas1, Carmen Azevedo1, Lacey Greene1, Anne-Laure Bauchet2, Erwan Jouannot2, Anne-Sophie Lacoste-Bourgeacq2, Isabelle Guizon2, Patrick Cohen2, Anne-Laure Naneix3, Ohad Ilovich1, Jordan Cisneros1, Krithika Rupanarayan1, Frederick T. Chin1, Andrei Iagaru1, Frederick M. Dirbas1, Amer Karam1, Sanjiv S. Gambhir1
- Department of Radiology, Bio-X program, Molecular Imaging Program at Stanford (MIPS), Division of Nuclear Medicine and Molecular Imaging, Stanford University, Stanford, CA, USA
- Sanofi Aventis Research and Development, Vitry-sur-Seine, France
- Centre de pathologie de Bichat, Paris, France
An antigen-binding fragment (BFab) derived from a tumor-associated mucin 1–sialoglycotope antigen (CA6) targeting antibody (huDS6) was engineered. We synthesized a companion diagnostic positron emission tomography (PET) tracer by radiolabeling BFab with [64Cu] to measure CA6 expression on cancer tissues prior to anti-human CA6 (huDS6-DM4 antibody-drug conjugate) therapy for ovarian and breast cancer patients. After chemotherapy, the ovarian patient received PET scan with 18F-2-fluoro-2-deoxyglucose ([18F]FDG: 10 mCi), followed by [64Cu]-DOTA-BFab ([64Cu]BFab; 5.5 mCi) 1 week later for PET scanning of CA6 expression and subsequent surgery. The breast cancer patient was treated with chemotherapy before primary tumor resection and subsequent [18F]FDG-PET scan. 4 weeks later the patient received of [64Cu]BFab (11.7 mCi) for CA6 PET scan. Whole body [18F]FDG-PET of the breast cancer patient indicated FDG-avid tumor metastases to the liver, bilateral hila and thoracic spine, but no uptake was observed for the ovarian patient. Each patient was also imaged by PET/CT with [64Cu]BFab at 1 and 24 hours after tracer administration. The [64Cu]BFab tracer was well tolerated by both patients without adverse effects, and no significant tracer uptake was observed in both patients. Immunohistochemistry (IHC) data indicated CA6 expressions were weak to intermediate and matched with the [64Cu]BFab-PET signals.
CovalX Technology Used
ImmunoPET tracer was developed by radiolabeling an engineered antibody fragment, BFab (~72 kDa), with PET radioisotope ([64CU]) to measure the carbonic anhydrase 6 (CA6) expression on cancer tissues in ovarian and breast cancer patients prior to anti-human CA6 therapy. Before performing any patients study, the quality assurance (QA) of DOTA-BFab, [64 CU] and [64 CU]BFab_PET Tracer was performed. One of the steps in this QA process included using Matrix-Assisted Laser Desorption Ionization modified with CovalX high-mass detector to detect the conjugation of mean DOTA chelates (c) per BFab (a) (~72 kDa).