Background: Lymphoseek is a radiopharmaceutical designed for sentinel lymph node (SLN) mapping. The purpose of this study was to compare Lymphoseek colon and gastric pharmacokinetics with filtered [Tc-99m]sulfur colloid (fTcSC). Methods: Eight anesthetized pigs received an endoscopic injection of Lymphoseek or fTcSC in the stomach and colon. Scintigraphy was obtained of both administration sites at 15-minute intervals up to 3 hours after injection, after which all SLNs were identified by a handheld gamma probe through a laparotomy incision. Isosulfan blue was administered at the injection site 5 minutes before SLN mapping. The percentage of injected dose (%ID) was measured for all harvested nodes, and the clearance half-life (T-c) was calculated for all injection sites. Results: The mean Lymphoseek clearance for colon (T-c, 2.56 +/- 1.04 hours) and gastric (T-c, 3.83 +/- 1.18 hours) injection sites was statistically faster (P = .030) compared with fTcSC (colon Tc, 14.98 +/- 3.41 hours; stomach T-c, 14.52 +/- 4.08 hours). After 3 hours, Lymphoseek exhibited a mean SLN %ID of 1.32% +/- 1.71% in the colon and 2.04% +/- 2.12% in the stomach; this was not statistically different from fTcSC (colon, .63% +/- .39%; stomach, 2.35% +/- 2.90%). SLN uptake of Lymphoseek was significantly different from second-echelon node %ID for the colon (P = .011) and gastric (P = .029) injection sites. All SLNs exceeded 10 times background, and there was no discordance between isosulfan blue and Lymphoseek or fTcSC. Conclusions: Three hours after colon stomach administration, Lymphoseek demonstrated rapid injection site clearance, detectable SLN uptake, and low second-echelon node uptake.