Abstract: The aim of this project is to evaluate the biodistribution of ¹⁷⁷Lu-DOTA-SP in normal mice and in PANC-1 tumor bearing nude mice and to pave the way for its potentially medical application. In this study, ¹⁷⁷Lu-DOTA-SP was successfully prepared with labeling yield of greater than 90% at optimized conditions and more than 98% of radiochemical purity after C18 Sep-Pak purification. ¹⁷⁷Lu-DOTA-SP showed good stability in saline and in 5% serum while it decomposed slowly in 10% serum. Biodistribution studies in normal mice showed high uptake of ¹⁷⁷Lu-DOTA-SP in the kidneys, indicating the excretion mainly by renal pathway. In addition, ¹⁷⁷Lu-DOTA-SP was washed out from the blood quickly. Biodistribution of ¹⁷⁷Lu-DOTA-SP in PANC-1 tumor bearing mice showed higher uptake in pancreatic tumor than that in normal pancreas, indicating the presence of NK-1 receptors in PANC-1 pancreatic tumor. However, from SPECT image, no radioactivity accumulation was observed in PANC-1 tumor. Further evaluation is needed to confirm its potential application for radiotherapy of pancreatic cancers.