Fig. 7: Molecular imaging of claudin-4 (CLDN4) in a PDAC mouse model.
A CLDN4-binding peptide and imaging scheme for study in tamoxifen-induced pancreatic cancer in the KPTC:KrasLSL-G12D/+;Trp53fl/fl;Rosa26LSL-tdTomato/LSL-tdTomato;Ptf1aCreER mouse model of PDAC (n = 6). Mice created with BioRender.com. B CLDN4 immunohistochemistry of organs (liver, lung, colon and pancreas) from the tamoxifen-induced PDAC mouse model. We used 64Cu-C4BP and demonstrated tumor-specific accumulation. This transgenic model expresses CLDN4 in both the pancreatic lesions and metastases (Met) after tumor induction. Representative image based on n = 6 mice with similar expression levels. C PET/CT maximum intensity projection (MIP) images acquired in the first 30 minutes after 64Cu-C4BP injection in the transgenic mouse model at 49 or 84 days after tamoxifen treatment. White arrowheads indicate accumulation of 64Cu-C4BP at the tumor sites. In the wild type mouse, 64Cu-C4BP is visible only in the clearance organs (kidney and bladder). D PET/CT slice images showing retention of 64Cu-C4BP within the pancreas (crosshair). E Time-activity curves (TACs) for blood, tumor, and kidney at 49 days (note that 64Cu-C4BP clears from the kidney). 2 ROIs per mouse were used to calculate intensity with a mouse sample of n = 6. F TACs for the pancreas and metastases at 84 days. G) Magnetic resonance imaging (MRI), PET/CT, and bright field images of abdominal region from the same mouse at 120 days after tamoxifen treatment. 64Cu-C4BP in the PET/CT image is well localized to the pancreatic lesion in the MRI and bright field images. Yellow arrowheads denote tdTomato signal (i.e. tumor lesions) in the bright field image in (G). H In the same model at ~84 days after tamoxifen treatment, ex vivo PET imaging with 64Cu-C4BP detects disease in the pancreas, colon and liver. Tumor cells express tdTomato in this model producing a red hue in the pancreas and colon. In this transgenic cancer model, liver accumulation is high and associated with metastasis. A small amount of activity accumulates in the liver due to clearance in the wild-type (WT) mouse. Graphs are presented as mean ± s.e.m. Abbreviations: L: liver, P: pancreas, St: stomach, S: spleen, C: colon, SI: small intestine, K: kidney, B: bladder, T: tumor. Source data are provided as a Source Data file.
