PubMed Health⌕ Search

Biomedical subjects

J C Reubi

Publications and source records attributed to J C Reubi.

At least 127 records · Page 7Linked to original sources
PubMed1993

Evaluation of a radiolabeled somatostatin analog (I-123 octreotide) in the detection and localization of carcinoid and islet cell tumors.

The purpose of this study was to evaluate the usefulness of a radiolabeled analog of somatostatin (iodine-123 octreotide) in the detection and localization of known carcinoid and islet cell tumors and to correlate tumor uptake with the presence or absence of somatostatin receptors. I-123 octreotide studies were performed in 28 patients. Whole-body and tomographic studies were performed over a 2-day period after injection. Twenty-two of the 28 patients underwent tumor biopsy, and samples were analyzed for the presence of somatostatin receptors. Tumors were best seen on scans obtained 1-4 hours after injection. Of the 28 patients, 22 had positive scans with uptake in tumors, three showed photon-deficient uptake in regions of known tumor, and three had negative scans. Seventeen patients in whom results of tumor biopsy were positive for somatostatin receptors had positive scans, and one patient in whom results of biopsy were negative for somatostatin receptors had a negative scan. Previously unsuspected lesions were detected on the I-123 octreotide scans in four of the 28 patients. I-123 octreotide appears to be a useful tracer for the localization of neuroendocrine tumors and, most likely, other soft-tissue tumors as well.

Adenoma, Islet Cell↗
PubMed1993

In vitro detection of somatostatin receptors in human tumors.

Somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred human tumors. SS-R have been 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 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 SS-R are rather differentiated, e.g. astrocytomas in contrast to glioblastomas, but exceptions exist such as high grade malignant lymphomas. An inverse relationship exists between SS-R 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 SS-R, characterized by low affinity for the octapeptide SS analog octreotide. The function of SS-R in human tumors differs according to tumor type, SS-R in pituitary and GEP tumors mediate hormone secretion inhibition, and have possibly some antiproliferative effects. In meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate cyclase activity, and weakly stimulates proliferation. Although 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1993

111In-octreotide scintigraphy in oncology.

Various tumors of neuroendocrine origin that have amine precursor and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous 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 in its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]-octreotide) was developed. This analogue is excreted mainly via the kidneys, 90% of the dose being present in the urine 24 h after injection. Using 111In-octreotide scintigraphy, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, 3 out of 3 unclassified apudomas, but none out of 18 exocrine pancreatic carcinomas were visualized. Also, 19 out of 19 carcinoids, 15 out of 15 glomus tumors, 8 out of 12 medullary thyroid carcinomas, 6 out of 6 small cell lung carcinomas, 4 out of 4 growth hormone-producing and 6 out of 9 clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD-cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied to visualize breast cancer, lymphomas and granulomas. In 39 out of 50 patients with breast carcinoma, 10 out of 11 patients with non-Hodgkin lymphomas, 3 out of 3 patients with Hodgkin's disease, and 8 out of 8 patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, but also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy revealed more tumor sites than did conventional imaging techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Apudoma↗
PubMed1993

Somatostatin (SRIH) messenger ribonucleic acid expression in human neuroendocrine and brain tumors using in situ hybridization histochemistry: comparison with SRIH receptor content.

Somatostatin (SRIH) receptors are expressed in a large number of neuroendocrine and brain tumors. To evaluate the potential of these tumors locally to produce the SRIH required to bind to SRIH receptors, we have investigated in 158 human tumors whether they express mRNA for SRIH, using in situ hybridization. Among 78 neuroendocrine tumors tested, 13 of 13 medullary thyroid carcinomas, 19 of 34 pheochromocytomas, 3 of 11 paragangliomas, 0 of 4 small cell lung cancers, 4 of 9 adrenal neuroblastomas, and 4 of 7 gastroenteropancreatic tumors contained SRIH mRNA. Among 47 central nervous system and meningeal tumors tested, including 23 meningiomas, 9 astrocytomas, 4 oligodendrogliomas, and 11 glioblastomas, none expressed SRIH mRNA. Unexpectedly, 16 of 33 ovarian tumors, including adenocarcinomas and borderline tumors, expressed SRIH mRNA. These results suggest that a large proportion of neuroendocrine tumors have the ability to express SRIH mRNA, whereas central nervous system tumors do not. The presence of SRIH mRNA in half of the tested ovarian tumors suggests that those tumors may be hormone producing and have neuroendocrine features. The presence of SRIH receptors in most of the neuroendocrine tumors together with the ability of many of those tumors to synthesize SRIH point toward an autocrine regulatory feedback mechanism of SRIH in these tissues.

Brain Neoplasms↗
PubMed1993

In vivo somatostatin receptor imaging in medullary thyroid carcinoma.

Using in vivo scintigraphy with the 111In-labeled somatostatin analog octreotide, tumor localizations were demonstrated in 11 of 17 patients (65%) with medullary thyroid carcinoma (MTC). Tumor localizations in the liver in 7 patients, and in the thyroid in 1 patient were not detected on octreotide scintigraphy, most probably because of normal uptake of labeled octreotide in these organs. Specific somatostatin receptors were demonstrated in vitro on all 5 investigated tumors which had also been visualized in vivo, as well as on 1 tumor that was not. Immunohistochemically, somatostatin was present in 1 of 6 tumors that were visualized in vivo, and in neither of 2 tumors that were not. The ratio of serum calcitonin over carcino-embryonic antigen concentrations was significantly higher in patients whose MTCs were visualized during octreotide scintigraphy than in those whose tumors were not. We have formed the following conclusions: 1) In the majority of patients with metastatic MTC, tumor sites can be visualized using octreotide scintigraphy, although this technique is insensitive in detecting liver metastases or intrathyroidal tumor; 2) The visualization of MTC during in vivo somatostatin receptor imaging correlates with the in vitro presence of somatostatin receptors; 3) The immunohistochemical presence of somatostatin in the tumor does not seem to influence the outcome of in vivo somatostatin receptor imaging; and 4) Higher serum calcitonin over carcino-embryonic antigen ratios in patients whose MTC is visualized during octreotide scintigraphy might imply that somatostatin receptors are present on more differentiated MTC.

Adult↗
PubMed1993

Human kidney as target for somatostatin: high affinity receptors in tubules and vasa recta.

Somatostatin (SRIH) receptors were identified in human kidneys by in vitro receptor autoradiography using 125I-[Tyr3]octreotide and 125I-[Leu8,D-Trp22,Tyr25]SRIH-28 as radioligands. Characterization of the binding demonstrated a single class of high affinity binding sites with a dissociation constant (Kd) of 0.5 nmol/L. Binding depended on GTP and magnesium and sodium concentrations. SRIH-14, SRIH-28, and octreotide were able to displace the radioligand in the high affinity range, whereas biologically inactive SRIH analogs or unrelated peptides were not. Microscopic localization of these receptors revealed binding over cortical and medullary areas. In the cortex, the receptors were located in the proximal tubules. No SRIH receptors were found in the glomeruli. In the medulla, the receptors were identified in high density in medullary vasa recta. A diffuse labeling of lesser density observed in the remaining medulla corresponded to collecting tubules. The receptor concentration was 32 fmol/mg protein in the renal cortex and 304 fmol/mg protein in the vasa recta. The receptors were undetectable in the rat kidney and are, thus, species dependent. SRIH receptors in the human kidney may be the molecular basis for the actions of SRIH on renal functions and may indicate a therapeutic potential for SRIH analogs in this tissue.

Arterioles↗
PubMed1993

Validation of somatostatin receptor scintigraphy in the localization 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 radionuclide-labeled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 32/37 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, and 5/7 small cell lung cancers. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems to be 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.

Adenoma, Islet Cell↗
PubMed1993

Metastatic carcinoid tumors and the malignant carcinoid syndrome.

Patients with metastatic carcinoid tumors and the malignant carcinoid syndrome have benefited immensely from diagnostic and therapeutic advances during the past decade. Magnetic resonance imaging and whole body scintigraphy with radiolabelled analogues of somatostatin have improved our ability to diagnose, detect, stage and follow response to therapy. Surgical, medical, and radiation therapy may all contribute to the management of these patients. This disease is variable in its presenting symptoms and the biologic behavior of the tumor. The spectrum of clinical manifestations varies depending upon the type and quantity of polypeptide hormones or biogenic amines being produced. Although the tumors are usually indolent in their growth, the more dedifferentiated or anaplastic tumors can be quite aggressive. Thanks to new treatments that are very effective in the subgroup of anaplastic neuroendocrine carcinomas it is vital to recognize this subset. As research scientists and clinicians we must be aware of the natural history of the disease in order to optimize each patient's treatment. This highly selective review focuses on studies performed in collaboration with Dr. Charles Moertel along with other colleagues at the Mayo Clinic, have done in the past few years.

Carcinoid Tumor↗
PubMed1993

The role of peptides and their receptors as tumor markers.

This article focuses on the role of peptides and peptide receptors as in vitro and in vivo markers for several human malignancies. Neuroendocrine or similar neoplasms can produce excessive quantities of peptides, which may be used as diagnostic markers. Recent studies demonstrate that several tumor types express excessive amounts of peptide receptors, which also may be considered as potentially valuable tumor markers. The considerable progress made in the field of peptide receptors in oncology, ranging from test-tube work in the laboratory to challenging diagnostic possibilities in the clinic, is reviewed in detail with particular emphasis on the peptide somatostatin and its receptors.

Animals↗
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↗