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

Freddy E Escorcia,Jeffrey M Steckler,Eric W Price,Jacob L Houghton,Sean D Carlin,Wolfgang W Scholz,Jason S Lewis,Dalya Abdel-Atti

doi:10.1007/s11307-018-1177-z

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.

Highlights

This year, there will be an estimated 79,030 new cases of and 16,870 deaths from urothelial carcinoma in the USA [1].While the majority of patients with bladder cancers present in early stages, those with locally advanced or metastatic disease have a 5-year survival rate of only 5 % [2]
In addition to standard cytotoxic therapy, the recent approval of antibodies targeting an immune checkpoint for patients with metastatic disease reaffirms the importance of host immunity in bladder cancer, especially since therapy for early-stage disease has long included an immune modulator, Bacillus Calmette-Guerín (BCG) [4]
To confirm presence of CA19.9 on human bladder cancer, flow cytometry and immunofluorescent studies of cells incubated with fluorescently labeled HuMab-5B1 were performed

Summary

Introduction

While the majority of patients with bladder cancers present in early stages, those with locally advanced or metastatic disease have a 5-year survival rate of only 5 % [2]. First-line therapy for these patients is combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or doublet therapy with gemcitabine plus cisplatin. These treatments have been shown to result in both higher. In addition to standard cytotoxic therapy, the recent approval of antibodies targeting an immune checkpoint for patients with metastatic disease reaffirms the importance of host immunity in bladder cancer, especially since therapy for early-stage disease has long included an immune modulator, Bacillus Calmette-Guerín (BCG) [4]. Novel therapeutic interventions targeting key oncogenic pathways altered in urothelial carcinoma expanded our therapeutic armamentarium and allow for precision tailoring of treatments for individual patients [5, 6]

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