Abstract
Pancreatic ductal adenocarcinoma (PDAC), accounting for 90–95% of all pancreatic tumors, is a highly devastating disease associated with poor prognosis. The lack of accurate diagnostic tests and failure of conventional therapies contribute to this pejorative issue. Over the last decade, the advent of theranostics in nuclear medicine has opened great opportunities for the diagnosis and treatment of several solid tumors. Several radiotracers dedicated to PDAC imaging or internal vectorized radiotherapy have been developed and some of them are currently under clinical consideration. The functional information provided by Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) could indeed provide an additive diagnostic value and thus help in the selection of patients for targeted therapies. Moreover, the therapeutic potential of β-- and α-emitter-radiolabeled agents could also overcome the resistance to conventional therapies. This review summarizes the current knowledge concerning the recent developments in the nuclear medicine field for the management of PDAC patients.
Highlights
Nuclear Medicine Department, Grenoble-Alpes University Hospital, 38000 Grenoble, France; Laboratoire Radiopharmaceutiques Biocliniques, Univ
In addition to Cancer-associated fibroblasts (CAF) targeting with the 18 F-FAP inhibitors (FAPI) agent that could efficiently detect Pancreatic ductal adenocarcinoma (PDAC) masses, radiotracers targeting fibronectin and matrix metalloproteinases (MMP) were recently developed for this application (Figure 1)
FAPI was labeled with 225 Ac (225 Ac-FAPI) and evaluated for its therapeutic potential in preclinical models of PDAC. 225 Ac-FAPI treatment of PANC-1 xenografted mice showed a significant decrease in tumor growth in comparison to control mice [69]
Summary
A condition of low oxygen availability, is a common feature of solid tumors affecting many aspects of tumor biology and promoting resistance to therapy [47]. In a constitutive hypoxic microenvironment, PDAC constitutively express the hypoxia-inducible factor-1 (HIF-1). HIF-1 expression levels are associated with tumor progression and metastasis [49,50]. The hypoxic environment of PDAC provides the rational for imaging hypoxia and investigating its role in the management of patients. 18 F-fluoromisonidazole (18 F-FMISO) and 18 F-fluoroazomycin arabinoside (18 F-FAZA), have been evaluated in PDAC. Their tumor uptakes were found to be weak, thereby limiting their interest in the imaging of PDAC [51,52]. Further investigations are needed to decipher the role of hypoxia imaging in the management of PDAC patients
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