PET Imaging of Hepatocellular Carcinoma Using ZD2-(68Ga-NOTA)

Olga Sergeeva,1 Yifan Zhang,1 Songqi Gao,2 E Ricky Chan,3 Maxim Sergeev,4 Renuka Iyer,5 Sandra Sexton,5 Norbert Avril,4 Zheng-Rong Lu,2 Zhenghong Lee1 1Department of Radiology, Case Western Reserve University, Cleveland, OH, USA; 2Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; 3Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA; 4Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 5Medical Oncology and Laboratory Animal Shared Resources, Roswell Park Cancer Institute, Buffalo, NY, USACorrespondence: Zhenghong Lee, Nuclear Medicine, Radiology, Case Western Reserve University, Bolwell S107, 11100 Euclid Avenue, Cleveland, OH, 44106, USA, Tel +1216-844-7920, Email zxl11@case.edu Zheng-Rong Lu, Biomedical Engineering, Case Western Reserve University, Wickenden 427, Mail Stop 7207, 10900 Euclid Ave, Cleveland, OH, 44106, USA, Tel +1 216-368-0187, Email zxl125@case.eduPurpose: We tested a recently developed short peptide radioligand for PET imaging of hepatocellular carcinoma (HCC) by targeting an oncoprotein, extra-domain B fibronectin (EDB-FN) in the tumor microenvironment.Methods: The radioligand consists of a small linear peptide ZD2 with 68Ga-NOTA chelator, and specifically binds to EDB-FN. PET images were acquired dynamically for 1 hour after intravenously (i.v.) injecting 37 MBq (1.0 mCi) of the radioligand into the woodchuck model of naturally occurring HCC. Woodchuck HCC originated from chronic viral hepatitis infection, which recapitulates the corresponding human primary liver cancer. The animals were euthanized post-imaging for tissue collection and validation.Results: For ZD2 avid liver tumors, the radioligand accumulation plateaued a few minutes after injection, while the liver background uptake stabilized 20 min post-injection. The status of EDB-FN in woodchuck HCC was confirmed by histology and validated by PCR and western blocking.Conclusion: We have showed the viability of using the ZD2 short peptide radioligand targeting EDB-FN in liver tumor tissue for PET imaging of HCC, which can potentially impact the clinical care for HCC patients.Keywords: peptide ligand, EDB fibronectin, positron emission tomography, woodchuck model