Correlative imaging of pancreatic ductal adenocarcinoma over-expressing CA19.9 antigen

66 Objectives The clinical diagnostic standard for primary and metastatic pancreatic ductal adenocarcinoma (PDAC) monitors elevated levels of systemic CA19.9 (sialyl Lewisa) antigen, making the tumor-associated antigen a potential non-invasive imaging biomarker. Here, we investigated the detection of PDAC by targeting CA19.9 with a new immunoPET imaging probe. Tumor delineation was validated using multimodal imaging techniques. Methods The desferrioxamine-conjugated fully human anti-CA19.9 monoclonal antibody 5B1 was radiolabeled with 89Zr. The pharmacological properties of this probe were elucidated via in vivo PET imaging and biodistribution using subcutaneous BxPC3 pancreatic cancer xenografts. We also utilized 18F-FDG-PET, magnetic resonance (MRI), computed tomography (CT) and bioluminescence (BLI) imaging in association with 5B1-PET in an orthotopic BxPC3 pancreas mouse model. Ex vivo autoradiography and histology studies examined tissue localization of 89Zr-5B1. Results Facile radiolabeling of 89Zr-5B1 produced excellent yields (>80%) and high specific activity (12.1±1.1 mCi/mg). 5B1-PET ROIs in orthotopic BxPC3 tumor models demonstrated high tumor accretion with maximum uptake at 48 h (30.7±6.6 %ID/g). Tumor-to-muscle ratios of 89Zr-5B1 at 48 h with 20.4±4.4 compared to 18F-FDG-PET with 3.5±1.1. MRI, CT, BLI and autoradiography confirmed the anatomical location of the tumor. Conclusions We have demonstrated the exquisite molecular specificity of 89Zr-5B1 for CA19.9 expressing PDAC. Correlative multimodality imaging confirms the observed tumor delineation of this radiotracer. In summary, 89Zr-5B1-PET has a high clinical potential as a screening tool for patients with CA19.9-expressing PDAC. Research Support Office of Science (BER), U.S. Department of Energy (DE-SC0002456) MSKCC Geoffrey Beene Cancer research grant (J.S.L.) NCI, National Institutes of Health (R42-CA-128362, W.W.S., P.O.L., R.S, X.W, G.R.)