Preclinical Evaluation of 68Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis - Sorbonne Université
Article Dans Une Revue Molecular Pharmaceutics Année : 2019

Preclinical Evaluation of 68Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis

Claire Provost
  • Fonction : Auteur
Faisal Alshoukr
  • Fonction : Auteur
Dominique Wendum
  • Fonction : Auteur
Anne Couvelard
  • Fonction : Auteur
Jacques Barbet
  • Fonction : Auteur
Patricia Forgez
  • Fonction : Auteur
Jean-Noël Talbot
  • Fonction : Auteur
Anne Gruaz-Guyon
  • Fonction : Auteur

Résumé

Neurotensin receptor 1 (NTSR1) is overexpressed in human pancreatic ductal adenocarcinoma (PDAC). Specific noninvasive positron-emission tomography (PET) imaging probes may improve the diagnostic accuracy and the monitoring of therapy for patients with PDAC. Here, we report the use of the 68 Ga-labeled neurotensin (NTS) analogue DOTA-NT-20.3 to image human PDAC in animal models and to discriminate tumors from pancreatitis. In addition to the preclinical study, two tissue microarray slides, constructed by small core biopsies (2−5) from standard paraffin-embedded tumor tissues, were used to confirm the high (78%) positivity rate of NTSR1 expression in human PDAC. PET imaging, biodistribution, blocking, and histology studies were performed in subcutaneous AsPC-1 pancreatic tumor-bearing mice. 68 Ga-DOTA-NT-20.3 PET images showed rapid tumor uptake and high contrast between the tumor and background with a fast blood clearance and a moderate accumulation in the kidneys. Ex vivo biodistribution showed low uptake in normal pancreas (0.22% IA/g) and in the remaining organs at 1 h postinjection, kidney retention (5.38 ± 0.54% IA/g), and fast clearance from blood and confirmed high uptake in tumors (5.28 ± 0.93% IA/g), leading to a tumor-to-blood ratio value of 6 at 1 h postinjection. The significant decrease of tumor uptake in a blocking study demonstrated the specificity of 68 Ga-DOTA-N-T20.3 to target NTSR1 in vivo. PET imaging was also conducted in an orthotopic xenograft model that allows tumors to grow in their native microenvironment and in an experimental pancreatitis model generated by caerulein injections. As opposed to 2-[ 18 F]fluoro-deoxyglucose, 68 Ga-DOTA-NT-20.3 distinguishes PDAC from pancreatitis. Thus, 68 Ga-DOTA-NT-20.3 is a promising PET imaging probe for imaging PDAC in humans.
Fichier principal
Vignette du fichier
2019 Prignon_Preclinical Evaluation of 68Ga-DOTA-NT-20.3.pdf (4.94 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03046483 , version 1 (15-12-2021)

Identifiants

Citer

Aurélie Prignon, Claire Provost, Faisal Alshoukr, Dominique Wendum, Anne Couvelard, et al.. Preclinical Evaluation of 68Ga-DOTA-NT-20.3: A Promising PET Imaging Probe To Discriminate Human Pancreatic Ductal Adenocarcinoma from Pancreatitis. Molecular Pharmaceutics, 2019, 16 (6), pp.2776 - 2784. ⟨10.1021/acs.molpharmaceut.9b00283⟩. ⟨hal-03046483⟩
61 Consultations
199 Téléchargements

Altmetric

Partager

More