Visualization of mouse pancreas architecture using MR microscopy.

Pancreatic diseases, which include diabetes, pancreatitis, and pancreatic cancer, are often difficult to detect and/or stage, contributing to a reduced quality of life and lifespan for patients. Thus, there is need for a technology that can visualize tissue changes in the pancreas, improve understanding of disease progression, and facilitate earlier detection in the human population. Because of low spatial resolution, current clinical magnetic resonance imaging (MRI) at low field strength has yet to fully visualize the exocrine, endocrine, vascular, and stromal components of the pancreas. We used high field strength magnetic resonance microscopy (µMRI) to image mouse pancreas ex vivo without contrast agents at high spatial resolution. We analyzed the resulting high-resolution images using volume rendering to resolve components in the pancreas, including acini, islets, blood vessels, and extracellular matrix. Locations and dimensions of pancreatic components as seen in three-dimensional µMRI were compared with histological images, and good correspondence was found. Future longitudinal studies could expand on the use of in vivo µMRI in mouse models of pancreatic diseases. Capturing three-dimensional structural changes through µMRI could help to identify early cellular and tissue changes associated with pancreatic disease, serving as a mode of improved detection in the clinic for endocrine and exocrine pathologies.

Phase I trial of fixed dose rate infusion gemcitabine with gefitinib in patients with pancreatic carcinoma.

PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine using a fixed dose rate infusion (FDRI) in combination with gefitinib in patients (pts) with pancreatic adenocarcinoma (PCa). PATIENTS AND METHODS: Patients with advanced PCa were given gemcitabine at the FDRI of 10 mg/m(2)/min IV on Days 1, 8, and 15 of a 28-day cycle. Dose levels of 1000, 1200, and 1500 mg/m(2) were evaluated. Oral gefitinib 250 mg was given daily. DLTs were defined as 2 instances of Grade 3 hematologic or 4 nonhematologic or any Grade 4 hematologic toxicity. At least 4 patients were treated at each dose level. Dose escalation occurred in the absence of DLTs. RESULTS: Five women and 8 men were enrolled. Median age was 59 and performance status 1. All had metastatic disease. Four patients received prior adjuvant chemoradiation for PCa, and one chemotherapy for lung cancer. Median cycles were 4 per patient. The MTD was 1,200 mg/m(2). Toxicity was predominantly hematologic. At 1,500 mg/m(2), 1 patient had Grade 4 granulocytopenia and 3 patients Grade 3 granulocytopenia. Overall, 8 patients (60 percent) developed Grade 1 or 2 acneiform rashes. One patient had Grade 3 vomiting; no significant diarrhea or liver toxicity was seen. There were no objective responses seen. Median time to progression and overall survival were 4.57 months and 7.13 months, respectively. CONCLUSION: Combining FDRI gemcitabine with gefitinib is feasible and tolerable. The recommended dose of gemcitabine is 1,200 mg/m(2) when used with gefitinib 250 mg daily.