Tumor-Specific Zr-89 Immuno-PET Imaging in a Human Bladder Cancer Model

Abstract

PurposeTumor-specific molecular imaging is an important tool for assessing disease burden and treatment response. CA19.9 is an important tumor-specific marker in several malignancies, including urothelial carcinoma. [89Zr]DFO-HuMab-5B1 (MVT-2163) is a CA19.9-specific antibody-based construct that has been validated in preclinical animal models of lung, colorectal, and pancreatic malignancies for positron emission tomography (PET) imaging and is currently in a phase I trial for pancreatic cancer (NCT02687230). Here, we examine whether [89Zr]DFO-HuMab-5B1 may be useful in defining urothelial malignancies.ProceduresSurface expression of CA19.9 was confirmed in the human bladder cancer line HT 1197. The radioimmunoconjugate [89Zr]DFO-HuMab-5B1 was injected into mice bearing HT 1197 xenografts, and followed by PET imaging, ex vivo experiments including biodistribution, histology and autoradiography, and analysis of blood samples for shed antigen levels were performed.Results[89Zr]DFO-HuMab-5B1 specifically accumulates in HT 1197 engrafted tumors when imaged with PET. Ex vivo biodistribution of organs and autoradiography of engrafted tumors confirm our construct’s specific tumor binding. The target antigen CA19.9 was not found to be shed in vitro or in vivo.Conclusions[89Zr]DFO-HuMab-5B1 can be used to delineate urothelial carcinomas by PET imaging and may provide tumor-specific information prior to, during, and after systemic therapies.

ImmunoPET Predicts Response to Met-targeted Radioligand Therapy in Models of Pancreatic Cancer Resistant to Met Kinase Inhibitors

“…Static scans (n=2) were recorded at the 24 h, 48 h, 72 h, and 120 h with a minimum of 12 million coincident events (8-25 min total scan time). Images were recorded on a microPET Focus scanner (Concorde Microsystems, Knoxville, Tennessee) as previously described 44, 45. All of the resulting images were analyzed using ASIPro VM software.…”

“…Orthotopically engrafted mice (n = 3) were administered [ 89 Zr]Zr-DFO-onartuzumab [1.8-2.7 MBq (50-72 μCi), 15 μg], via tail vein injection and images were acquired at 24 h, and 120 h. Static scans were recorded on an Inveon PET/CT scanner (Siemens Healthcare Global) at the various time points with a minimum of 30 million coincident events (10-30 min total scan time). Data sorting, reconstruction, and normalization were performed as previously reported 44, 45. Combined PET/CT images were processed using Inveon Research Workplace software and optimized to show localization of the PET signal.…”

“…Tissues were cut in a series of 10-μm sections. Autoradiography was performed as previously described 44. Following autoradiography, sequential sections were submitted to the Molecular Cytology Core Facility at MSKCC for automated Met, and Ki-67 immunohistochemistry.…”

PET/CT Imaging with an 18F-Labeled Galactodendritic Unit in a Galectin-1–Overexpressing Orthotopic Bladder Cancer Model

“…The radiotracers 11 C-choline, 11 C-methionine, and 11 C-acetate (all of which have minimal urinary excretion) have been investigated as alternatives to 18 F-FDG for PET/CT in BCa patients ( 23 ). In the context of BCa PET imaging, our group has recently demonstrated in subcutaneous HT1197 bladder tumors the utility of an antibody-based approach using a carbohydrate-antigen 19.9–specific human antibody HuMab-5B1 (MVT-5873) ( 24 ).…”

ImmunoPET as Stoichiometric Sensor for Glypican-3 in Models of Hepatocellular Carcinoma

“…Accordingly, tumorselective PET imaging agents could be quite valuable in HCC. Radiolabeled tumor antigen-selective antibodies have been developed as immunoPET theranostic agents and have demonstrated success in preclinical (6)(7)(8)(9)(10)(11) and clinical studies (12)(13)(14)(15)(16)(17)(18). Conventionally, given the 3-7 day blood half-life of most full length antibodies (19), radioisotopes with corresponding physical half-lives such as Zr-89 (3.5 days) or I-124 (4.2 days) are utilized for antibody labeling.…”