Translational molecular imaging in exocrine pancreatic cancer

Abstract

Effective treatment for pancreatic cancer remains challenging, particularly the treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than 95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and radiotherapy are all too common, and many patients die soon after diagnosis. Here, we make the case for the increased use of molecular imaging in PDAC preclinical research and in patient management.

Keywords: Molecular imaging; PET; Pancreatic ductal adenocarcinoma; Preclinical developments; SPECT.

Fig. 1

¹⁸F-FDG PET imaging for initial staging of PDAC in an 80-year-old woman. a The initial staging MR image shows a hypoenhancing mass in the pancreatic body (arrows) that has resulted in pancreatic ductal dilatation. b The PET/CT image shows corresponding FDG uptake in the mass (arrows). c, d Additionally, the fused PET/CT image (c) and PET-only image (d) show an ¹⁸F-FDG-avid peripancreatic node (arrows). Adapted from Yeh et al. [7]

Fig. 2

¹⁸F-FLT PET image in a 70-year-old patient with a 2-cm tumour in the pancreatic head [19]

Fig. 3

Coronal PET image of a mouse bearing a GRP78-positive BxPC-3 tumour xenograft 48 h after injection of the ⁶⁴Cu-labelled anti-GRP78 antibody MAb159 [44]

Fig. 4

MRI imaging in an orthotopic mouse model of pancreatic cancer 4 months after surgical implantation of the tumour showing the difference in signal between intravenously administered conventional contrast agent (free Magnevist) and the TfRscFv-Lip-Mag complex [50]

Fig. 5

a Mesothelin in PDAC (protein atlas: 11/12 positive [56]). b ⁸⁹Zr-MMOT0530 PET/CT image in a patient with PDAC shows the primary tumour (red oval), as well as uptake in healthy liver [55]

Fig. 6

⁶⁸Ga-avebehexin PET image (maximum-intensity projection, 60 min after injection) of a H2009-bearing SCID mouse. The tumour is indicated by the arrow. Blad. bladder, Kid. kidneys [63]

Fig. 7

Coronal small-animal PET images of HT29 tumour-bearing immunodeficient mice injected with ⁶⁸Ga-8, a radiolabelled neurotensin peptide analogue. The mouse on the right received a blocking dose of cold, unlabelled compound to saturate the receptor [71]

Fig. 8

a Representative in-vivo image of a human primary pancreatic cancer tumour xenograft in a mouse after administration of a Cy5 fluorophore-labelled cathepsin E substrate [74]. b A Cy5.5-labelled cathepsin B-targeting DARPin is taken up in a 4T1 allograft murine breast tumour (red circle), but not in a healthy mammary fat pad (black circle) [75]

Fig. 9

NIR fluorescence imaging in a mouse bearing subcutaneous PDAC tumours acquired 72 h after injection of CEA-targeting ssSM3E/800CW or F73/800CW [78]

Fig. 10

a CEA expression in human PDAC tissue (protein atlas [56]) b SPECT/CT image in a 38-year-old patient acquired 24 h after injection of ¹¹¹In-IMP288 (185 MBq, 25 μg) pretargeted with 75 mg of TF2 (1-day interval) [80]

Fig. 11

PET, PET/CT, and near infrared imaging in an orthotopic PDAC mouse model using a ⁸⁹Zr-labelled anti-CA19.9 antibody (LN lymph node, M metastasis, T tumour) [84]

Fig. 12

Monitoring 5-FU therapy with ⁸⁹Zr-anti-γH2AX-TAT: PET/CT images show coronal (top) and transaxial (bottom) sections intersecting the centre of the allograft tumour (dotted circles) [13]. Tumour uptake of a nonspecific control antibody (RIgG) was not different between 5-FU-treated and vehicle-treated animals