Clinical Studies and Molecular Pathology

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7.2.3. Core C. Clinical studies and molecular pathology Core Leader: Jacques Van Dam Investigators: James Crawford, Jay Pasricha, Shiro Urayama Clinical studies - testing of new probes The testing of new probes will be undertaken first in small animal models (to determine the focality of the uptake) and then in large animals using endoscopic imaging techniques. Both safety and efficacy will be judged using animal models. As small animals and even large animal models do not perfectly predict biological behavior in humans, we will move to human studies once safety and efficacy in animals have been established. Peptide probes will be administered topically during routine endoscopy (Hsiung P. et al., 2008). Target tissue (polyps, inflammation, control regions of relatively normal mucosa) will be washed with water to remove excess mucus. Approximately 3-6 mL of peptide at a concentration of 100 uM will be topically administered using a standard spray catheter (Olympus washing pipe, Olympus America, Inc.; Center Valley, PA). Excess peptide will be rinsed away and imaging undertaken. For deeper target structures such as neoplastic lesions (esophageal, gastric, rectal cancers) and associated enlarged lymph nodes of uncertain nature (benign, inflammatory, metastatic), peptide probes will require parenteral administration. Again, safety and efficacy will be judged in animal models prior to human study. Due to the circulating time, it is anticipated that peptides will require administration in advanced of the imaging procedure. The optimal time of localization of peptide with the greatest signal- to-noise ratio will be determined in animal models prior to human study. Once approved for human study, patient selection will include those with known gastrointestinal malignancy referred for endosonographic staging procedures and, as controls, those patients with inflammatory conditions (esophagitis, colitis, gastritis) in which enlarged lymph nodes may be inflammatory rather than neoplastic. Many cancer patients will then be referred for surgical resection and lymph node harvest. Excised lymph nodes will be assess for metastatic disease (standard of care) and will serve as "gold standard." Many patients with benign disease (fulminant colitis, chronic pancreatitis) will also undergo surgical resection and again, harvested lymph nodes will be histopathologically assessed.