Imaging Macrophage Accumulation in a Murine Model of Chronic Pancreatitis with ¹²⁵I-Iodo-DPA-713 SPECT/CT

Abstract

Pancreatitis remains a diagnostic challenge in patients with mild to moderate disease, with current imaging modalities being inadequate. Given the prominent macrophage infiltration in chronic pancreatitis, we hypothesized that ¹²⁵I-iodo-DPA-713, a small-molecule radiotracer that specifically targets macrophages, could be used with SPECT/CT to image pancreatic inflammation in a relevant experimental model. Methods: Chronic pancreatitis was induced with cerulein in C57BL/6 mice, which were contrasted with saline-injected control mice. The animals were imaged at 7 wk after induction using N,N-diethyl-2-(2-(3-¹²⁵I-iodo-4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide (¹²⁵I-iodo-DPA-713) SPECT/CT or ¹⁸F-FDG PET/CT. The biodistribution of ¹²⁵I-iodo-DPA-713 was determined under the same conditions, and a pair of mice was imaged using a fluorescent analog of ¹²⁵I-iodo-DPA-713, DPA-713-IRDye800CW, for correlative histology. Results: Pancreatic ¹²⁵I-iodo-DPA-713 uptake was significantly higher in treated mice than control mice (5.17% ± 1.18% vs. 2.41% ± 0.34% injected dose/g, P = 0.02), as corroborated by imaging. Mice imaged with ¹⁸F-FDG PET/CT showed cerulein-enhanced pancreatic uptake in addition to a moderate signal from healthy pancreas. Near-infrared fluorescence imaging with DPA-713-IRDye800CW showed strong pancreatic uptake, focal liver uptake, and gastrointestinal uptake in the treated mice, whereas the control mice showed only urinary excretion. Ex vivo fluorescence microscopy revealed a large influx of macrophages in the pancreas colocalizing with the retained fluorescent probe in the treated but not the control mice. Conclusion: These data support the application of both ¹²⁵I-iodo-DPA-713 SPECT/CT and DPA-713-IRDye800CW near-infrared fluorescence to delineate pancreatic, liver, or intestinal inflammation in living mice.