Molecular Targeted Positron Emission Tomography Imaging and Radionuclide Therapy of Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has an inauspicious prognosis, mainly due to difficulty in early detection of the disease by the current imaging modalities. The upcoming development of tumour-specific tracers provides an alternative solution for more accurate diagnostic imaging techniques for staging and therapy response monitoring. The future goal to strive for, in a patient with PDAC, should definitely be first to receive a diagnostic dose of an antibody labelled with a radionuclide and to subsequently receive a therapeutic dose of the same labelled antibody with curative intent. In the first part of this paper, we summarise the available evidence on tumour-targeted diagnostic tracers for molecular positron emission tomography (PET) imaging that have been tested in humans, together with their clinical indications. Tracers such as radiolabelled prostate-specific membrane antigen (PSMA)—in particular, 18F-labelled PSMA—already validated and successfully implemented in clinical practice for prostate cancer, also seem promising for PDAC. In the second part, we discuss the theranostic applications of these tumour-specific tracers. Although targeted radionuclide therapy is still in its infancy, lessons can already be learned from early publications focusing on dose fractioning and adding a radiosensitiser, such as gemcitabine.

Synthesis and Preclinical Evaluation of Three Novel 68Ga-Labeled Bispecific PSMA/FAP-Targeting Tracers for Prostate Cancer Imaging

“…Despite many effective PSMA-targeting radiotherapeutic agents being developed, patients with low to no PSMA expression are not eligible for these emerging PSMA-targeted radioligand therapies and still have very limited treatment options. Since FAP and PSMA are both expressed in prostate cancer and other cancers such as pancreatic cancer [ 25 , 35 , 36 , 37 , 38 ], the use of PSMA/FAP bispecific radioligands is expected to increase lesion detection sensitivity and treatment efficacy. The ultimate goal of this reported research is to develop 68 Ga-labeled PSMA/FAP bispecific tracers with comparable or higher tumor uptake when compared to the monospecific tracers, [ 68 Ga]Ga-FAPI-04 and [ 68 Ga]Ga-HTK03041, a PSMA-targeting tracer previously reported by our group [ 34 ].…”

m6A-modified circRNA MYO1C participates in the tumor immune surveillance of pancreatic ductal adenocarcinoma through m6A/PD-L1 manner

“…Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with high mortality and tens of thousands of newly diagnosed cases are reported by global statistics [1,2]. Worldwide, the widespread application of screening has reduced the global morbidity and mortality associated with PDAC [3].…”

Novel Strategies to Address Critical Challenges in Pancreatic Cancer

“…Moreover, higher glucose uptake can also be present in inflammatory diseases, including pancreatitis. In their review, Poels et al suggest that Fibroblast Activation Protein Inhibitor (FAPI) and Prostate-Specific Membrane Antigen (PSMA) are highly promising novel tracer targets [ 7 ]. PSMA is a transmembrane protein that not only seems to be present in prostate cancer cells but also in tumour-associated neovasculature [ 7 ].…”

“…In their review, Poels et al suggest that Fibroblast Activation Protein Inhibitor (FAPI) and Prostate-Specific Membrane Antigen (PSMA) are highly promising novel tracer targets [ 7 ]. PSMA is a transmembrane protein that not only seems to be present in prostate cancer cells but also in tumour-associated neovasculature [ 7 ]. When comparing PDAC with pancreatitis or healthy tissue using immunohistochemistry, the expression of PSMA was high and low (H-score 0), respectively [ 8 ].…”

“…Of note, not only are these tumour-targeted imaging tracers important for diagnostic purposes, they can also prove pivotal as radiopharmaceutical carriers for targeted therapy [ 7 , 10 ]. In a phase III trial, 177 Lu-PSMA-617 treatment was compared to standard care in 831 patients with highly lethal castration-resistant prostate cancer [ 11 ].…”