Current and Future Trends in Early Detection of Pancreatic Cancer: Molecular Targets and PET Probes

Abstract

Early detection of pancreatic cancer has been a long-standing challenge in determining prognosis and management of the deadly disease. Although the incidence of pancreatic cancer is low (2% of all malignancies), it is the fourth leading cause of deaths attributable to cancer in the U.S. A major cause for the high mortality rate, which exceeds 85%, is the difficulty in diagnosing the disease early in its development. The relative lack of reliable diagnostic tools to screen patients who are asymptomatic prior to the aggressive progression of disease has been the primary contributing factor in the high mortality rate in this patient population. Indeed, 80-90% of patients with pancreatic cancer have relatively small unresectable tumors at the time of diagnosis. Therefore, there is an unmet need for a highly sensitive diagnostic imaging modality to detect early-stage pancreatic cancer, as this may save the lives of many thousands of patients. Many literature reviews have been published on various aspects of pancreatic cancer, including biology, screening, and therapy; however, limited information is available on early detection, especially the use of highly sensitive modalities such as positron emission tomography (PET). Current [(18)F]FDG/PET imaging combined with CT (PET/CT) lacks the necessary sensitivity and specificity for detection of small lesions (~2-3 mm) of pancreatic cancer that may be resectable and curable. Furthermore, accumulation of [(18)F]FDG in inflammatory tissue is a major problem; therefore, an appropriate PET tracer that is both highly sensitive and specific for carcinoma is necessary for PET imaging of early stage pancreatic cancer. This review focuses on early detection of pancreatic cancer by PET, including new targets and the development and application of new PET tracers.

Early Detection of Pancreatic Cancer: Opportunities and Challenges

“…Several groups have investigated novel imaging agents that are coupled to 18 F. These remain in the early stages of development, including investigations of lactose analogues and the hepatocarcinoma-intestine-pancreas/pancreatic-associated protein (HIP/PAP). 190 Other strategies to detect pancreatic cancer with molecular imaging agents include targeting proteins that are overexpressed by the cancer (eg, mesothelin), signaling pathways (eg, epidermal growth factor receptor), tumor stroma (eg, hedgehog signaling, vascular endothelial growth factor), and other targets that are associated with the disease (eg, plectin-1, MUC1). 191 Another molecular imaging method that is of interest for early detection is hyperpolarized MRI, which can identify metabolic aberrations in the pancreas that indicate preneoplasia.…”

Recent advances in understanding pancreatic cancer

“…Cross-sectional imaging is used for screening patients with hereditary pancreatitis, as the calcium load in these individuals will prevent adequate EUS assessment. Future developments with positron emission tomography (PET) and the use of molecular imaging techniques that target proteins overexpressed by the tumour, signalling pathways, or the stroma may improve detection of early lesions 39 , 40 . Further development of hyperpolarised magnetic resonance imaging, which can identify metabolic aberrations in the pancreas indicative of pre-neoplasia, may also prove to be a useful adjunct to early detection and screening 41 .…”

The clinical application of 18F-FDG PET/CT in pancreatic cancer: a narrative review

“…Considering that 18 F-FDG PET/CT has certain limitations in the diagnosis of pancreatic cancer, new targets and new PET tracers are continually being developed and used ( 88 ). Flores et al developed the first 18 F-labeled lactose analog that targets HIP/PAP and applied it to the early detection of pancreatic cancer by PET in an animal model ( 89 ).…”