A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake

A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-pres erved phenotype, Tumor cells in nude mice expressed identical neuroendocrin e markers as the original tumor, including somatostatin receptors (somatost atin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT 2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatos tatin analogue In-123-octreotide and the catecholamine analogue I-123-metai o-dobenzylguanidine. The biokinetics of the somatostatin analogue In-111-oc treotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors . Immunocytochemical and ultrastructural studies confirmed the neuroendocri ne differentiation. The human origin of transplanted tumor cells was confir med by cytogenetic and fluorescence it situ hybridization analyses, Spontan eous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid , from tumor cells was demonstrated. The tumor cells increased their [Ca2+] (i) in response to beta -adrenoceptor stimulation (isoproterenol) and K+-de polarization. All somatostatin receptor subtypes could be demonstrated in c ultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatos tatin receptor and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.