Neuroendocrine tumor cells frequently overexpress somatostatin receptors at their cell surfaces. To evaluate the possibility of using the somatostatin analog 111In-DTPA-D-Phe1-octreotide for radiation therapy, we studied the binding and subsequent internalization of 111In into three types of cultured human neuroendocrine tumor cells. METHODS Primary cultures of gastric carcinoid, midgut carcinoid and glucagonoma cells were incubated with 111In-DTPA-D-Phe1-octreotide and cell-surface bound, internalized and released 111In activity was measured. Electron microscopic autoradiography was also performed. RESULTS All three cell types specifically (80%-95%) bound 111In-DTPA-D-Phe1-octreotide and internalized 111In. After 1 hr pulse incubation with 111In-DTPA-D-Phe1-octreotide, there was an initial decrease in intracellular 111In to about 50% during the subsequent 6-hr incubation. Almost no further release was observed during the remaining 18-42 hr studied. Autoradiography showed that the internalized 111In was found in the cytoplasm and nucleus in the midgut carcinoid cells. CONCLUSIONS Indium-111 DTPA-D-Phe1-octreotide might be useful for radiation therapy of patients with surgically incurable tumors having high somatostatin receptor densities.