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J C Reubi

Publications and source records attributed to J C Reubi.

At least 19 recordsLinked to original sources
PubMed1992

Somatostatin receptors in human renal cell carcinomas.

The presence of somatostatin receptors was evaluated in samples of 39 surgically removed human renal cell carcinomas with receptor autoradiography on tumor sections by using iodinated [Tyr3]octreotide as the radioligand. All types, grades and stages of tumors were represented. Twenty-eight of 39 renal cell carcinomas (72%) were shown to be somatostatin receptor positive. The receptors were saturable, of high affinity (KD = 0.8 nM), and were specific for somatostatin and bioactive somatostatin analogues. No evident correlations were found between the status of somatostatin receptors in the tumor and the age or sex of the patients, the histopathological type or grade of the tumor, or the tumor-node-metastasis stage of the disease. However, numerous cases considered to be of poor prognosis were somatostatin receptor positive. No functional correlates for these receptors have been established, although the presence of somatostatin receptors in human kidneys and somatostatin effects on renal tubular functions in normal human volunteers have been reported. In a patient scanned in vivo for islet cell carcinoma with an 123I-labeled somatostatin analogue, bilateral renal cell carcinomas were also visualized; multiple bilateral renal cell carcinomas were identified on the 1- and 4-h images taken after injection of 123I-labeled somatostatin analogue. In conclusion, the high incidence of somatostatin receptors in renal cell carcinomas may have diagnostic value when performing in vivo imaging of somatostatin receptors and it may have potential therapeutic implications.

Adult↗
PubMed1992

Somatostatin receptor imaging of endocrine gastrointestinal tumors.

UNLABELLED: Somatostatin receptors are present on various tumors of neuroendocrine origin. We recently developed a technique for the in vivo visualization of somatostatin receptor positive tumors, which offers a powerful alternative to tumor imaging with labeled monoclonal antibodies. Instead of injecting radiolabeled antibodies against the somatostatin receptor, we labeled a somatostatin analogue ([Tyr3]-octreotide) which is known to bind specifically to the somatostatin receptor, and injected this labeled hormone analogue in order to visualize somatostatin receptor positive tumors. We previously reported the successful visualization of the primary tumors or metastases of various endocrine gastrointestinal tumors after injection of the iodinated somatostatin analogue [123I-Tyr3]-octreotide. The primary tumors or metastases of 12 out of 13 carcinoids, 3 out of 3 gastrinomas, 2 out of 4 insulinomas, and 1 out of 1 somatostatinoma were visualized. Using 111In-coupled octreotide, we were able to visualize 19 out of 19 carcinoids, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, and 3 out of 3 non-functioning endocrine pancreatic tumors, but none of 18 exocrine pancreatic tumors. In a large proportion of patients with endocrine gastrointestinal tumors, previously unrecognized metastases were demonstrated. Also, the absence or presence of in vivo visualization of these tumors after the injection of radiolabeled octreotide seems to predict the ability of octreotide therapy to control symptoms caused by hormonal secretion from these tumors. IN CONCLUSION: 111In-octreotide scintigraphy is a simple and sensitive technique for localizing of the primary tumor and its metastases in the majority of patients with carcinoids or endocrine pancreatic tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine Gland Neoplasms↗
PubMed1992

In vitro and in vivo detection of somatostatin receptors in human malignant lymphomas.

A wide variety of primary and metastatic human neoplasms express somatostatin receptors (SS-Rs). We evaluated the SS-R status of malignant lymphomas that had been surgically removed from 31 patients by use of in vitro SS-R autoradiography with the SS analog 125I-[Tyr3]-octreotide as radioligand. Of 11 low-grade-malignancy B-cell non-Hodgkin's lymphomas, 10 were SS-R-positive, with a high receptor density restricted to the neoplastic follicles. All of the 8 intermediate-grade lymphomas were SS-R-positive. Of the B-cell lymphomas of high-grade malignancy, 7 out of 10 were SS-R-positive, often with a high density of receptors. One T-cell lymphoma and one Hodgkin's lymphoma were also positive. SS-Rs were of high affinity (KD = 1.2 nM) and specific for bioactive SS analogs. In 4 patients, the lymphomas were localized in vivo by use of gamma-camera scintigraphy after i.v. injection of the SS analog 111In-[DTPA-D-Phe1]-octreotide. Hot spots, identified in all 4 patients, corresponded to SS-R-positive malignant-lymphoma tissue, as confirmed by receptor autoradiography of the surgically removed tumors. Our data show that SS-Rs are valuable pathobiochemical tissue markers and potentially useful in vivo diagnostic tools for human malignant lymphomas.

Adolescent↗
PubMed1992

Preferential location of somatostatin receptors in germinal centers of human gut lymphoid tissue.

Somatostatin receptors were evaluated in four human gut-associated lymphoid tissues (palatine tonsils, ileal Peyer patches, vermiform appendix, and colonic solitary lymphatic follicles) using receptor autoradiography on tissue sections incubated with 125I[Tyr3]octreotide. All four tissues were somatostatin-receptor positive; the receptors were preferentially located in the germinal centers, with the luminal part of the center more strongly labeled than the basal part. The corona of the follicles and the primary follicles without germinal centers did not display somatostatin receptors. The receptors were of high affinity (Kd = 1.3 +/- 0.6 nmol/L) and specific for somatostatin. Displacement by nanomolar concentrations of somatostatin 14, somatostatin 28, and octreotide was observed, as was guanosine triphosphate dependency. The gastrointestinal mucosa and the plexus submucosus and myentericus also contained somatostatin receptors. These data strongly suggest that the germinal centers of the gut-associated lymphoid tissue are a site of action of somatostatin. It possibly mediates antiproliferative effects and inhibits immunoglobulin synthesis in the activated lymphoid cells. The human gut represents a multifaceted target for somatostatin action, in which at least three different tissues (mucosa, nerve plexus, and lymphoid tissue) are involved.

Humans↗
PubMed1992

111In-octreotide scintigraphy in oncology.

Various tumors of neuroendocrine origin that have amine precursor uptake and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous (IV) injection of the somatostatin analogue, [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks to its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]- octreotide) was developed. This analogue is excreted mainly via the kidneys, with 90% of the dose being present in the urine 24 hours after injection. Using 111In-octreotide scintigraphy, seven of seven gastrinomas, four of seven insulinomas, one of one glucagonomas, three of three unclassified APUDomas, and none of 18 exocrine pancreatic carcinomas were visualized. Also, 19 of 19 carcinoids, 15 of 15 glomus tumors, eight of 12 medullary thyroid carcinomas, six of six small-cell lung carcinomas, four of four growth hormone-producing and six of nine clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied in visualizing breast cancer, lymphomas, and granulomas. In 39 of 50 patients with breast carcinoma, 10 of 11 patients with non-Hodgkin's lymphomas, three of three patients with Hodgkin's disease, and eight of eight patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, and also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy showed more tumor sites than did conventional imaging techniques. The results of imaging in vivo correlated with the somatostatin-receptor status on the tumors in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1992

In vitro detection of somatostatin receptors in human tumors.

Somatostatin receptors (SSR) have been identified in membrane homogenates or tissue sections from several hundred human tumors. SSR have been found in most neuroendocrine tumors, ie, growth hormone (GH)- and thyrotropin (TSH)-producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC), and small-cell lung carcinomas. SSR have also been found in the majority of malignant lymphomas, in several brain tumors (all meningiomas, most astrocytomas), and in breast tumors. The majority of tumors expressing SSR are rather differentiated, eg, astrocytomas in contrast to glioblastomas, but exceptions such as high-grade malignant lymphomas do exist. An inverse relationship exists between SSR and receptors for epidermal growth factor in lung tumors, glial tumors, and most breast tumors, whereas meningiomas express both receptors simultaneously. A minority of tumors such as ovarian tumors, MTC, and insulinomas express a subtype of SSR characterized by low affinity for the octapeptide SS analogue, octreotide. The function of SSR in human tumors differs according to tumor type; SSR in pituitary and GEP tumors mediate hormone secretion inhibition and possibly have some antiproliferative effects. However, in meningiomas, activation of SSR inhibits forskolin-stimulated adenylate cyclase activity and weakly stimulates proliferation. Although SSR seem to mediate antiproliferative effects in animal models and cell lines of lymphomas and breast and lung tumors, such an effect has not yet been convincingly documented in human primary tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗
PubMed1992

Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications.

Somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred tumors. SS-R were found in most neuroendocrine tumors, i.e. GH and TSH producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary thyroid carcinomas (MTC) and small cell lung carcinomas. SS-R were also expressed in a majority of malignant lymphomas, in several brain tumors (all meningiomas, most astrocytomas) and in breast tumors. The majority of tumors expressing SS-R are rather differentiated (i.e. astrocytomas vs glioblastomas), but exceptions exist (high grade malignant lymphomas). An inverse relationship exists between SS-R and receptors for epidermal growth factor (EGF-R) incidence in lung tumors, glial tumors and most breast tumors, whereas meningiomas express simultaneously both receptors. A minority of tumors (ovarian tumors, MTC, insulinomas) express a subtype of SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function mediated by SS-R in human tumors may differ according to the tumor type. SS-R in pituitary and GEP tumor mediate hormone secretion inhibition with, in addition, possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Whereas SS-R seem to mediate antiproliferative effects in animal models and cell lines of lymphomas, breast and lung tumors, such an effect has not yet been convincingly documented in human primary tumors. The clinical implications of the presence of SS-R in tumors are manyfold: (1) as a predictive marker for efficient therapy with octreotide in pituitary and GEP tumors; (2) as a diagnostic marker: for pathobiochemical classification of tumors, using in vitro detection methods; for clinical evaluation using in vivo scanning techniques; (3) as a prognostic marker; and (4) as a potential radiotherapeutic target.

Animals↗
PubMed1992

Somatostatin receptor imaging in the diagnosis and treatment of neuroendocrine tumors.

Somatostatin analogs are used in the control of hormonal hypersecretion and tumor growth of patients with acromegaly, islet cell carcinomas and carcinoids. Recently we showed that somatostatin receptor positive tumors can be visualized in vivo after the administration of radioactive isotope-labelled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 30/31 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, 5/7 small cell lung cancers, 6/7 neuroblastomas, 38/49 primary breast cancers, and 0/18 pancreatic adenocarcinomas. Also 11/11 meningiomas, 4/4 astrocytomas and 0/3 glioblastomas could be visualized. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It is an in vivo method for the recognition of neuroendocrine cancers. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems of prognostic value in certain types of cancer. This scintigraphic method might help in patient selection for clinical trials with somatostatin analogs in the treatment of neuroendocrine cancers.

Endocrine Gland Neoplasms↗
PubMed1992

Identification of somatostatin and gastrin receptors on enterochromaffin-like cells from Mastomys gastric tumors.

Histamine-secreting enterochromaffin-like (ECL) cells of the gastric fundus of the Mastomys can develop into solid ECL cell tumors, either spontaneously or after induction by acid inhibition. We used this tumor tissue to perform in vitro receptor autoradiography for somatostatin (SS), gastrin, and substance-P, using, respectively, [125I]Tyr3-octreotide, [125I]gastrin-17, and [125I]Bolton-Hunter-labeled substance-P as radioligands. A high density of SS receptors was found in the nontumor fundic mucosa, where gastrin receptors were only barely detectable. However, in the group of spontaneously developing ECL cell tumors, a high density of SS and gastrin receptors was observed, homogeneously distributed in the tumor tissue. In addition, the loxtidine-induced ECL cell tumors expressed a high density of SS and gastrin receptors. The receptors were specific for the respective peptide and of high affinity, with a dissociation constant (Kd) of 0.90 nM for SS receptor and 0.87 nM for gastrin receptors. No substance-P receptors were detected on the ECL cell tumors, although they were present in the muscle layers of the Mastomys gastric fundus. These results demonstrate that ECL-derived tumors express receptors for both SS and gastrin. This observation is consistent with the proposal that there is substantial regulation of the histamine-producing ECL cell by SS and gastrin. The presence of gastrin receptors is compatible with a role for gastrin as a trophic factor in ECL cell hyperplasia and neoplasia. The expression of SS receptors may be of diagnostic and therapeutic relevance in the regulation of ECL function and neoplastic transformation.

Animals↗
PubMed1992

Dissociation of antiproliferative and antihormonal effects of the somatostatin analog octreotide on 7315b pituitary tumor cells.

The somatostatin (SS) analog octreotide has been successfully used in the treatment of (neuro)endocrine tumors. The mechanism of action of the tumor (growth) inhibitory action by octreotide is not fully understood. We have investigated the effect of octreotide on 7315b rat pituitary tumor cell growth, PRL release, and intracellular PRL concentrations in vitro. When cultured in medium with 10% fetal calf serum, the number of high affinity SS receptors increased with increasing culture time. On days 7, 14, and 21 of culture, the number of SS receptors amounted to 978 +/- 217, 3588 +/- 705, and 5865 +/- 3332 fmol/mg protein, respectively, whereas they were not measurable on day 0. From days 0-7, 7-14, and 14-21 of culture, octreotide (1 pM to 1 microM) inhibited PRL release and the intracellular PRL concentration, with IC50 values in the nanomolar range. However, no inhibition of cell growth was observed by these octreotide concentrations from day 0-7 of culture, while octreotide inhibited cell growth in a dose-dependent fashion from days 7-14 and 14-21 of culture (maximal inhibition by 25% and 26%, respectively). In a series of nine consecutive experiments we found a significant positive correlation between the percent inhibition of cell growth induced by 1 microM octreotide and the number of SS receptors on 7315b cells (r = 0.7865; P = 0.012). Inhibition of PRL release did not correlate with SS receptor numbers. Octreotide (1 microM) inhibited forskolin (0.5 microM)-stimulated cell growth and intracellular PRL concentrations, while in the presence of a high concentration of forskolin (10 microM), octreotide had no effect on forskolin-stimulated cell growth and intracellular PRL concentrations. In addition, its PRL release inhibitory effect was significantly lower in forskolin-stimulated cultures. Pretreatment of the cells with pertussis toxin (10 micrograms/liter) completely prevented the inhibition of cell growth by octreotide and diminished the inhibitory effect of octreotide on PRL release. Finally, 1 microM octreotide significantly inhibited forskolin-stimulated cAMP production (by 29% and 53% on days 7 and 14 of culture, respectively). We conclude that 1) octreotide inhibits 7315b rat pituitary tumor cell proliferation via a pertussis toxin-sensitive GTP-binding protein- and adenylate cyclase-dependent mechanism; and 2) the number of SS receptors on 7315b pituitary tumor cells may determine whether octreotide exerts a direct antiproliferative effect, whereas its antihormonal effect occurs in the presence of relatively low numbers of SS receptors. This suggests a dissociation of the antiproliferative and antihormonal effects induced by octreotide.

Adenylate Cyclase Toxin↗
PubMed1992

Somatostatin inhibits the activity of adenylate cyclase in cultured human meningioma cells and stimulates their growth.

It has been reported previously that most human meningiomas have receptors for somatostatin. Here we report the results of investigations of the effect of somatostatin and the somatostatin analog octreotide on the growth in vitro of human meningioma cells. Neither somatostatin nor its analog showed a direct growth inhibitory action on cultured human meningioma cells. Rather, there was a slight but significant stimulation of growth in the presence of somatostatin. The somatostatin receptors in meningioma tissue were shown to be functional since somatostatin inhibited forskolin-stimulated formation of cAMP by meningioma membranes. In addition, cAMP inhibited the growth of cultured meningioma cells. We conclude that the stimulation by somatostatin of the growth of human meningioma cells in vitro is caused by its inhibitory effect on cAMP formation. These results suggest that therapeutic trials of patients with (recurrent) inoperable meningiomas with somatostatin analogs have to be carried out with great caution.

Adenylyl Cyclase Inhibitors↗
PubMed1992

In vitro and in vivo detection of somatostatin receptors in pheochromocytomas and paragangliomas.

Fifty-one adrenal pheochromocytomas and 14 paragangliomas were evaluated for somatostatin (SRIH) receptor content with in vitro autoradiography on tissue sections from surgically removed tumors, using iodinated 125I[Tyr]3 octreotide as radioligand. Thirty-seven of 51 pheochromocytomas were SRIH receptor positive (73%), as well as 13 of 14 paragangliomas (93%). These SRIH receptors were of high affinity, pharmacologically specific for SRIH and localized on the tumor tissue. Using in vivo imaging techniques with radiolabeled SRIH analogs, paragangliomas could be visualized in five patients, as well as pheochromocytomas in two of three patients. All tumors tested subsequently in vitro (n = 7) were shown to contain SRIH receptors. A majority of pheochromocytomas were also shown to have a high tumoral SRIH content as measured by immunohistochemical techniques. Detection of SRIH messenger RNA in pheochromocytomas by in situ hybridization indicated that the SRIH was produced in the tumors. A weak inverse correlation was observed between SRIH receptor status and tumoral SRIH content, suggesting that SRIH receptors may be down-regulated by high levels of endogenous SRIH in some tumors. There was no correlation between the SRIH receptor status and sex, age, tumor size, benign vs. malignant tumor, or urinary metanephrine excretion. These tumors were also analyzed for allelic losses on various chromosomes and showed significant loss of heterozygosity (LOH) on chromosomes 1p, 3p, 17p, and 22q. All eight tumors with LOH on chromosome 1p were SRIH receptor positive (100%), whereas only 6 of 11 tumors without LOH on 1p (55%) were SRIH receptor positive, suggesting a correlation between LOH on 1p and SRIH receptor positive status. SRIH receptors thus represent a consistent pathobiochemical marker for most of these adrenal and extra-adrenal tumors. In addition, these receptors may be of potential interest for the in vivo localization of these tumors.

Adrenal Gland Neoplasms↗
PubMed1992

Clinically nonfunctioning pituitary adenoma and octreotide response to long term high dose treatment, and studies in vitro.

We have studied seven patients with a clinically nonfunctioning or alpha-subunit-secreting pituitary macroadenoma, four of whom received long term, high dose octreotide treatment. We have attempted to correlate the presence of somatostatin receptors (SS-R) in the adenomas and the outcome of octreotide treatment, as measured by tumor size, improvements in visual field defects, and hormonal response. The presence of SS-R in the pituitary adenomas was demonstrated in vivo using [111indium]octreotide scintigraphy and in vitro by autoradiography of tissue fragments obtained after transsphenoidal surgery. Adenomas from six of the seven subjects were SS-R positive. High dose (1200 micrograms, sc, daily) octreotide treatment was given to four subjects, three of whom were SS-R positive. Improvement of the visual field defects was observed in three of four patients (including the SS-R-negative subject), although no computed tomographic scan-assessed tumor size reduction was found. Two of four patients showed small but significant reductions in serum FSH concentrations (to 83% and 93% of initial values) with treatment. These in vivo responses to high dose octreotide treatment could not be predicted by pretreatment responses to 200 micrograms TRH or 100 micrograms octreotide. Tissue fragments for cell culture were obtained from six patients, and in vitro release of gonadotropins and/or alpha-subunit could be demonstrated in five cultures. In vitro, octreotide (10 nmol/L) significantly decreased gonadotropiin or subunit release in three of five cultures, whereas bromocriptine (10 nmol/L) significantly reduced the release in four of five cultures and to a significantly greater extent than octreotide. In conclusion, in six of seven patients with a clinically nonfunctioning or alpha-subunit-secreting pituitary adenoma, SS-R were demonstrated in the tumor. In vitro incubation of adenoma cells with octreotide resulted in mild inhibition of gonadotropin or alpha-subunit release. Although in vivo long term treatment with high doses of octreotide did not result in substantial tumor size reduction, improvement of visual field defects was observed in three of four subjects.

Adenoma↗
PubMed1992

Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide.

Scintigraphy with 123I-Tyr-3-octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-octreotide, has consequently been proposed. DTPA-D-Phe-1-octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-octreotide and with 111In-DTPA-D-Phe-1-octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.

Adult↗
PubMed1992

Somatostatin analogs in the treatment of acromegaly.

Medical therapy of acromegaly with the somatostatin analog octreotide is very successful. Both clinical symptomatology and hormonal hypersecretion by the growth hormone-secreting pituitary adenomas are controlled, and peripheral IGF-I levels also return to near normal levels. Tumor shrinkage is observed in most patients. Somatostatin analogs can be used after noncurative surgery and for a limited period after radiotherapy, and octreotide pretreatment might improve the outcome of surgery.

Acromegaly↗
PubMed1991

Establishment and characterization of a human carcinoid in nude mice and effect of various agents on tumor growth.

The authors have established a long-term tissue culture cell line (BON) derived from a metastatic human carcinoid tumor of the pancreas. The cells have been in continuous passage for 46 months. Tissue culture cells produce tumors in a dose-dependent fashion after SC inoculation of cell suspensions in athymic nude mice. BON tumors, grown in nude mice, are histologically identical to the original tumor; they possess gastrin and somatostatin receptors, synthesize serotonin and chromogranin A, and have a doubling time of approximately 13 days. The antiproliferative effects of the long-acting somatostatin analogue, SMS 201-995 (300 micrograms/kg, t.i.d.), and 2% alpha-difluoromethylornithine on BON xenografts in nude mice were examined. Tumor size was significantly decreased by day 14 of treatment with either agent and at all points of analysis thereafter until the animals were killed (day 33). In addition, tumor weight, DNA, RNA, and protein contents were significantly decreased in treated mice compared with controls. Establishment of this human carcinoid xenograft line, BON, provides an excellent model to study further the biological behavior of carcinoid tumors and the in vivo effect of chemotherapeutic agents on tumor growth.

Animals↗
PubMed1991

In vivo application of [111In-DTPA-D-Phe1]-octreotide for detection of somatostatin receptor-positive tumors in rats.

Radioiodinated somatostatin analogues are useful ligands for the in vitro and in vivo detection of somatostatin receptors. [111In-DTPA-D-Phe1]-octreotide, a somatostatin analogue labeled with a different radionuclide, also binds specifically to somatostatin receptors in vitro. In this study we investigated its in vivo application in the visualization of somatostatin receptor-positive tumors in rats. The distribution of the radiopharmaceutical was investigated after intravenous injection in normal rats and in rats bearing the somatostatin receptor-positive rat pancreatic carcinoma CA 20948. After injection the radiopharmaceutical was rapidly cleared (50% decrease in maximal blood radioactivity in 4 min), predominantly by the kidneys. Excreted radioactivity was mainly in the form of the intact radiopharmaceutical. Ex vivo autoradiographic studies showed that specific accumulation of radioactivity occurred in somatostatin receptor-containing tissue (anterior pituitary gland). However, in contrast to the adrenals and pituitary, the tracer accumulation in the kidneys was not mediated by somatostatin receptors. Increasing radioactivity over the somatostatin receptor-positive tumors was measured rapidly after injection and the tumors were clearly visualized by gamma camera scintigraphy. In rats pretreated with 1 mg octreotide accumulation of [111In-DTPA-D-Phe1]-octreotide in the tumors was prevented. Because of its relatively long effective half-life, [111In-DTPA-D-Phe1]-octreotide is a radionuclide-coupled somatostatin analogue which can be used to visualize somatostatin receptor-bearing tumors efficiently after 24 hr, when interfering background radioactivity is minimized by renal clearance. This is an advantage over the previously used [123I-Tyr3]-octreotide which has a shorter effective half-life and shows high abdominal interference due to its hepato-biliary clearance. Therefore, [111In-DTPA-D-Phe1]-octreotide seems a better alternative for scintigraphic imaging of somatostatin receptor-bearing tumors.

Animals↗