Translational molecular imaging in exocrine pancreatic cancer

Cornelissen, Bart; Knight, James C.; Mukherjee, Somnath; Evangelista, Laura; Xavier, Catarina; Caobelli, Federico; Vecchio, Silvana Del; Rbah-Vidal, Latifa; Barbet, Jacques; Jong, Marion de; Leeuwen, Fijs W. B. van

doi:10.1007/s00259-018-4146-5

Cited by 17 publications

(18 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A major problem in the management of PDAC is that the disease remains practically asymptomatic, and has already disseminated by the time of diagnosis. Treatment may be comprised of surgical resection followed by chemo/radiotherapy, but outcomes are rather limited, with most patients dying soon after diagnosis and the average survival not surpassing 28 months [42]. It is therefore imperative to make available effective theranostic tools to combat PDAC, including radiolabeled NTS1R-directed probes.…”

Section: Introductionmentioning

confidence: 99%

Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors

Kanellopoulos

Nock

Krenning

et al. 2020

IJMS

View full text Add to dashboard Cite

Background: The overexpression of neurotensin subtype 1 receptors (NTS1Rs) in human tumors may be elegantly exploited for directing neurotensin (NT)-based radionuclide carriers specifically to cancer sites for theranostic purposes. We have recently shown that [99mTc]Tc–DT1 ([99mTc]Tc–[N4–Gly7]NT(7–13)) and [99mTc]Tc–DT5 ([99mTc]Tc–[N4–βAla7,Dab9]NT(7–13)) show notably improved uptake in human colon adenocarcinoma WiDr xenografts in mice treated with neprilysin (NEP) inhibitors and/or angiotensin-converting enzyme (ACE) inhibitors compared with untreated controls. Aiming toward translation of this promising approach in NTS1R-positive pancreatic ductal adenocarcinoma (PDAC) patients, we now report on the impact of registered NEP/ACE inhibitors on the performance of [99mTc]Tc–DT1 and [99mTc]Tc–DT5 in pancreatic cancer models. Methods: The cellular uptake of [99mTc]Tc–DT1 and [99mTc]Tc–DT5 was tested in a panel of pancreatic cell lines, and their stability was assessed in mice treated or not treated with Entresto, lisinopril, or their combinations. Biodistribution was conducted in severe combined immunodeficiency (SCID) mice bearing pancreatic AsPC-1 xenografts. Results: The Entresto + lisinopril combination maximized the metabolic stability of the fast-internalizing [99mTc]Tc–DT1 in mice, resulting in notably enhanced tumor uptake (7.05 ± 0.80% injected activity (IA)/g vs. 1.25 ± 0.80% IA/g in non-treated controls at 4 h post-injection; p < 0.0001). Conclusions: This study has shown the feasibility of optimizing the uptake of [99mTc]Tc–DT1 in pancreatic cancer models with the aid of clinically established NEP/ACE inhibitors, in favor of clinical translation prospects.

show abstract

Section: Introductionmentioning

confidence: 99%

Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors

Kanellopoulos

Nock

Krenning

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…The 5-year survival rate for PDAC patients averages 5-8% and has not changed over the past 4 decades. [1][2][3][4] Therefore, development of a detection method for PDAC at an earlier stage of disease progression is strongly desirable.…”

Section: Introductionmentioning

confidence: 99%

Development and characterization of a 68Ga-labeled A20FMDV2 peptide probe for the PET imaging of αvβ6 integrin-positive pancreatic ductal adenocarcinoma

Ueda

Higaki

et al. 2020

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

“…It combines the target specificity and selectivity of antibodies and variants toward a biomarker with a given imaging technique’s capabilities. Of importance, functional tumor biomarker expression changes can occur earlier than changes in the lesion size as assessed on morphological imaging [ 127 ].…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography

González-Gómez

Pazo‐Cid

Sarria

et al. 2021

JCM

View full text Add to dashboard Cite

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) by current imaging techniques is useful and widely used in the clinic but presents several limitations and challenges, especially in small lesions that frequently cause radiological tumors infra-staging, false-positive diagnosis of metastatic tumor recurrence, and common occult micro-metastatic disease. The revolution in cancer multi-“omics” and bioinformatics has uncovered clinically relevant alterations in PDAC that still need to be integrated into patients’ clinical management, urging the development of non-invasive imaging techniques against principal biomarkers to assess and incorporate this information into the clinical practice. “Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. Furthermore, we define the different components of immuno-PET and summarize the existing applications of this technique in PDAC. The development of novel immuno-PET methods will make it possible to conduct the non-invasive diagnosis and monitoring of patients over time using in vivo, integrated, quantifiable, 3D, whole body immunohistochemistry working like a “virtual biopsy”.

show abstract

Translational molecular imaging in exocrine pancreatic cancer

Cited by 17 publications

References 92 publications

Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors

Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors

Development and characterization of a 68Ga-labeled A20FMDV2 peptide probe for the PET imaging of αvβ6 integrin-positive pancreatic ductal adenocarcinoma

Diagnosis of Pancreatic Ductal Adenocarcinoma by Immuno-Positron Emission Tomography

Contact Info

Product

Resources

About