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While Octreoscan 111 has been shown to localize the majority of amine precursor uptake and decarboxylation system (APUD) cell tumors as well as various other somatostatin-positive tumors, this technique may also be useful in a number of other circumstances. These include prediction of tumors that will respond to octreotide therapy, identification of covert metastases, intraoperative identification of tumors, and postoperative surveillance. Use of an alternative isotope may provide a vehicle for the administration of local therapeutic radiation to tumor cells. The precise efficacy of Octreoscan 111 in the identification of lesions smaller than 3 cm with low-density somatostatin-2 receptor expression remains to be determined.

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Background/Aims: Hypergastrinemia, induced by sustained suppression of gastric acid secretion, is associated with gastric enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumor formation. We examined the effect of a selective Hi-histamine antagonist, terfenadine, on gastric mucosal cell proliferation to determine whether histamine might modulate ECL cell generation. Methods: The rodent mastomys received the H₂-antagonist loxtidine (2 g/l drinking water) alone or in combination with terfenadine (0.5 g/l or 35 mg/l drinking water) for 120 days. Controls received water or terfenadine alone. Serum gastrin levels and tissue histamine content were assayed by radioimmu-noassays, and tissue chromogranin levels determined (Western blot analysis). In vivo cell proliferation was measured by bromodeoxyuridine (BrdU, 200 mg/kg/day, 3 days) incorporation. Gastric mucosal thickness was determined, ECL cell number was assessed, and the percentage of proliferating ECL cells quantitated. To evaluate the direct action on ECL cells we then studied the effect of terfenadine on histamine secretion and DNA synthesis (BrdU uptake) in an isolated preparation (∼ 90% pure) of ECL cells. Results: Loxtidine increased serum gastrin levels, mucosal thickness, tissue chromogranin levels, tissue histamine content, BrdU incorporation, ECL cell number, and proliferating ECL cells (all parameters p < 0.05). Terfenadine alone, irrespective of dosage, had no significant effect. The high dose in combination with loxtidine significantly inhibited the increase in tissue chromogranin levels, tissue histamine content, ECL cell number and proliferating ECL cells (p < 0.05), but did not alter other parameters, compared to loxtidine alone. The low dose did not alter the loxtidine-induced changes. In pure isolated ECL cells, terfenadine did not alter histamine secretion either alone or in combination with gastrin (10 nM). DNA synthesis was significantly inhibited by terfenadine (IC₅₀ 10^-10M). Conclusions: Terfenadine specifically inhibited the effect of loxtidine-induced ECL cell proliferation in vivo and significantly inhibited ECL cell DNA synthesis in vitro. We postulate that histamine, through an H₁ receptor, positively modulates gastric ECL cell proliferation.

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The mastomys rodent exhibits a genetic propensity to develop gastric carcinoid tumors. Utilizing acid inhibitory pharmacotherapy (histamine-2 receptor antagonists and proton pump inhibitors), we have demonstrated transformation from normal to neoplastic enterochromaffin-like (ECL) cells in a well-defined fashion over a period of 4 months. In addition, we have demonstrated inhibition of tumor growth with either somatostatin or histamine-1 receptor antagonists (terfenadine and cyproheptadine). In order to define the regulation of growth and secretion of transformed ECL cells, we developed an isolated pure ECL cell system. ECL cells secrete histamine in response to gastrinergic (gastrin), muscarinic (carbachol), and β-adrenergic (isoproterenol) stimulation. Both cAMP and intracellular calcium-dependent mechanisms are involved in the process of histamine secretion.