Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1835664 (TOC)
 2,763 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although somatostatin-based peptide receptor imaging (sst-PRI) and peptide receptor radiotherapy (sst-PRRT) of human endocrine tumours and their metastases has become a valuable method, the experience with radiohalogenated sst-directed peptides has so far been disappointing. To extend the broad spectrum of radiohalogens with suitable radionuclide properties for sst-PRI and PRRT, new strategies in ligand development are required. The major drawbacks to be overcome include fast hepatic uptake, high abdominal background activity and low tumour uptake. Recently we introduced radiolabelled glycated octreotides as a new series of sst-binding radiotracers with excellent physicochemical characteristics. In this study we compared [(125)I]Tyr(3)-octreotide ([(125)I]TOC, ( 1)), [(125)I]Tyr(3)-octreotate ([(125)I]TOCA, ( 2)) and a carbohydrated octreotide derivative, maltotriose-[(125)I]Tyr(3)-octreotate ([(125)I]Mtr-TOCA, ( 3)) to evaluate the effect of single C-terminal oxidation and simultaneous N-terminal carbohydration. The biodistribution was compared in nude mice bearing AR42J tumour xenografts. Compared with ( 1), activity uptake of ( 2) and ( 3) at 1 h was decreased in intestine [36% ( 2), 72% ( 3)], liver [62% ( 2), 79% ( 3)] and kidney [34% ( 2), 41% ( 3)], respectively. Blood clearance was fast for all compounds investigated. Using ( 1) as reference, tumour uptake of ( 2) and ( 3) was 3.8- and 4.3-fold higher at 1 h p.i. At 1 h the tumour-to-blood ratio of ( 3) was 28.2+/-7.3, and the tumour-to-muscle ratio, 147+/-48. Specificity of tumour uptake was demonstrated in AR42J tumour-bearing mice by pretreatment with 0.8 mg TOC/kg 5 min prior to injection of ( 3). In cells transfected with sst1-sst5, the binding profile of I-Mtr-TOCA revealed a very high affinity and selectivity for sst2. In a first scintigraphic [(123)I]Mtr-TOCA study of a patient with a carcinoid of the small intestine with known peritoneal carcinomatosis and a solitary liver metastasis, all tumour tissues, including the liver metastasis, were well defined and clearly visible as soon as 30 min p.i. Based on these encouraging findings we conclude that carbohydration is a powerful strategy for the development of new radiolabelled sst-binding peptides and may represent a general method to improve pharmacokinetics of other peptide radioligands. [(123)I]Mtr-TOCA is a very promising new candidate for sst-directed PRI.
 ...
PMID:Comparison of radioiodinated TOC, TOCA and Mtr-TOCA: the effect of carbohydration on the pharmacokinetics. 1180 4

This study assessed the clinical usefulness of a new technetium-99m labelled somatostatin analogue from the standpoint of oncological diagnostics. The study group comprised 40 patients in whom malignant neoplasms (32 primary and 8 metastatic) had been diagnosed. Among the primary tumours there were 21 cases of lung cancer (2 small cell and 19 non-small cell), seven pituitary adenomas (five hormonally active and two inactive), one liposarcoma, two carcinoids and one breast carcinoma. The metastatic tumours consisted of three malignant melanomas, one phaeochromocytoma, one prostatic cancer, one leiomyosarcoma, one pancreatic carcinoma ectopically secreting ACTH and one carcinoid of the thymus. The radiopharmaceutical 99mTc-EDDA/HYNIC-Tyr3-octreotide was administered i.v. at an activity of 740-925 MBq. The imaging comprised a whole-body scan and a single-photon emission tomography acquisition. Positive scintigrams were obtained in all cases of small cell and non-small cell lung cancer, four out of five hormonally active pituitary adenomas, one out of two cases of carcinoid, the liposarcoma and the breast cancer. Neoplastic metastases were visualised in two out of three patients with melanoma and in patients with phaeochromocytoma, ACTH-secreting pancreatic carcinoma and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, in the leiomyosarcoma and in the case of metastasis from prostatic carcinoma. The results of this pilot study indicate that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for imaging of a wide range of primary and metastatic tumours. Special attention should be paid to the successful imaging of all cases of non-small cell lung cancer.
 ...
PMID:Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a preliminary communication. 1512 15

Forty-three consecutive patients with solitary pulmonary nodules (SPNs) on chest radiographs were studied scintigraphically after administration of the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC. The objective of the study was to assess the usefulness of the procedure for differentiation of SPNs as malignant or benign. The administered activity was 740-925 MBq, and a single-photon emission computed tomography imaging technique was employed. Verification of the nodule aetiology was based on histology or cytology and bacteriology. A stable tumour size on chest radiography for at least 3 years was accepted as an additional criterion of benignity. In 29 patients, nodules were found to be malignant. The diagnoses included ten adenocarcinomas, five squamous cell carcinomas, two large cell carcinomas, six non-small cell lung cancers without specification of the more detailed morphology, two small cell lung cancers, two typical carcinoids and two metastatic tumours (leiomyosarcoma and malignant melanoma). In 14 patients the following benign tumours were diagnosed: four tuberculomas, one other granuloma, three hamartomas, one non-specific inflammatory infiltrate, one abscess, one peripheral carcinoid with the morphological characteristics of a benign tumour, one ectopic lesion of thyroid tissue and two benign tumours of unspecified aetiology with a stable size over 3 and 5 years respectively. Positive scintigraphic results were obtained in 26 of the 29 patients (90%) with malignant SPNs; among these, 24 of the 25 (96%) cases of primary pulmonary carcinoma yielded positive results. The remaining two false negative cases were the metastatic tumours, liposarcoma and melanoma. Of the 14 benign lesions, ten (71%) did not accumulate the radiopharmaceutical. The remaining four benign tumours that were visible on scintigrams comprised one tuberculoma, one hamartoma, one abscess and one case in which the diagnosis could not be established (the tumour had a stable size over 3 years). In conclusion, scintigraphy with (99m)Tc-EDDA/HYNIC-TOC appears to be an effective procedure for differentiation between malignant and benign SPNs. A fully credible assessment of the clinical efficacy of this procedure requires further study in a larger number of patients.
 ...
PMID:99mTc-EDDA/HYNIC-TOC scintigraphy in the differential diagnosis of solitary pulmonary nodules. 1502 63

Tetraamine-[Tyr3]octreotate (Demotate) is a somatostatin (SST) analogue that can be easily labeled with 99mTc at high specific activities and showed promising preclinical properties for SST receptor scintigraphy. This study reports on the first intra-patient comparison of 99mTc-Demotate and another 99mTc-labeled SST analogue, 99mTc-EDDA/HYNIC-TOC (HYNIC-TOC). Five patients with carcinoid tumors (n = 2) and endocrine pancreatic tumors (n = 3) were investigated with both radiopharmaceuticals. 99mTc-Demotate rapidly visualized somatostatin receptor positive tumors as early as 15 minutes post-injection (p.i.) with maximum tumor uptake and tumor/organ ratios already 1 hour p.i. Organs of predominant physiological uptake were the spleen and the kidneys with no intestinal excretion detectable up to 24 hours. 99mTc-Demotate exhibited faster pharmacokinetic properties compared to HYNIC-TOC. Tumor/organ ratios at equivalent time points were higher or comparable for 99mTc-Demotate in three patients with a matching scan result. Equivocal findings were observed in two patients, i.e. comparable uptake behavior in larger lesions with differences in smaller ones. 99mTc-Demotate is a promising agent for somatostatin receptor scintigraphy providing images of excellent quality as early as 1 hour after injection.
 ...
PMID:99mTc-N4-[Tyr3]Octreotate Versus 99mTc-EDDA/HYNIC-[Tyr3]Octreotide: an intrapatient comparison of two novel Technetium-99m labeled tracers for somatostatin receptor scintigraphy. 1506 14

The clinical usefulness of a new 99mTc-labeled somatostatin analogue has been studied from the standpoint of oncological diagnostics. The group of patients studied included 40 individuals with diagnosed malignant neoplasms (32 primary and 8 metastatic). Among the primary tumors were 7 pituitary adenomas (5 hormonally active and 2 inactive), 1 liposarcoma, 2 carcinoids, 1 breast carcinoma, and 21 cases of lung cancer (2 small cell and 19 non-small cell) were represented. The metastatic tumors consisted of: 3 malignant melanomas, 1 pheochromocytoma, 1 prostatic cancer, 1 leiomyosarcoma, 1 pancreatic carcinoma ectopically secreting ACTH, and 1 carcinoid of the thymus. The radiopharmaceutical, 99mTc-EDDA/HYNIC-octreotide, was i.v. administered at the activity of 740-925 MBq. The imaging was comprized of a whole-body scan and single photon emission computed tomography. Positive scintigrams were obtained in 4 of 5 hormonally active pituitary adenomas, in 1 of 2 cases of carcinoid, in liposarcoma, breast cancer, and all cases of small cell (SCLC) and non-small cell lung cancer (NSCLC). The neoplastic metastases were visualized in 2 of 3 cases of melanoma and in patients with pheochromocytoma, pancreatic carcinoma secreting ACTH, and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, leiomyosarcoma, and in cases of metastasis from the prostatic carcinomas. The results of this pilot study indicated that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for the imaging of a wide range of primary and metastatic tumors. More detailed indications for the clinical usefulness of the new tracer for the imaging of selected tumor types require studies on much larger groups of patients. Special attention should be paid to the successful imaging of all cases of NSCLC.
 ...
PMID:Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a pilot study. 1518 7

Fifty consecutive patients with solitary pulmonary nodules (SPN) on chest radiographs were studied scintigraphically after the administration of a somatostatin analog 99mTc-EDDA/HYNIC-TOC. The activity amounted to 740-925 MBq and a single photon emission computed tomography (SPECT) technique was applied. Verification of the nodule etiology was based on histology or cytology and bacteriology. As additional criterion for nodule benignity, its stable size in a chest radiograph for at least 3 years was accepted. In 31 patients, malignant etiologies of nodules were found. The diagnoses included: 11 adenocarcinomas, 6 squamous-cell carcinomas, 2 large-cell carcinomas, 6 nonsmall-cell lung cancers (NSCLC) of unspecified, more detailed morphology, 2 small-cell lung cancers (SCLC), 2 typical carcinoids, and 2 metastatic tumors: leiomyosarcoma and malignant melanoma. In 19 patients, the following benign tumors were diagnosed: 6 tuberculomas, 2 other granulomas, 4 hamartomas, 2 nonspecific inflammatory infiltrates, 1 abscess, 1 peripheral carcinoid of morphological characteristics of a benign tumor, 1 ectopic lesion of thyroid tissue, and 2 benign tumors of unspecified etiology, with stable size over 3 and 5 years. Positive scintigraphic results were obtained in 28 of 31 patients (90%) with malignant SPNs; among these there were 26 of 27 (96%) cases of primary pulmonary carcinoma. The remaining 2 false-negative cases included metastatic tumors: liposarcoma and melanoma. Among 19 benign lesions, 15 (79%) did not accumulate the radiopharmaceutical. The remaining 4 tumors visible on scintigrams included: 1 tuberculoma, 1 hamartoma, 1 abscess, and 1 case of nonestablished diagnosis (with stable size over 3 years). In conclusion, scintigraphy with 99mTc-EDDA/HYNIC-TOC appears to be an effective procedure for differentiation between malignant and benign SPNs.
 ...
PMID:Efficacy of 99mTc-EDDA/HYNIC-TOC scintigraphy in differential diagnosis of solitary pulmonary nodules. 1565 Apr 54

The authors review the most important clinical aspects of carcinoid tumors. Carcinoid tumors originating in neuroendocrine cells are rare, usually slowly-growing neoplasms, however, they may present as aggressive and rapidly progressing tumors. Epidemiologic data indicates that their prevalence is gradually increasing, which may be explained, at least in part, by the development and wider use of advanced diagnostic methods. A considerable proportion of patients with neuroendocrine tumors are symptom-free, whereas others may have carcinoid syndrome or symptoms of other endocrine syndromes. Early diagnosis may be established by the measurement of biochemical markers (serum chromogranin A, urinary 5-hydroxyindoleacetic acid) and advanced localization methods. A considerable number of patients are diagnosed at the late stages of the disease; in these cases surgical cure is not possible but surgical and/or interventional radiologic procedures which reduce tumoral mass should be still considered. The most effective drugs for symptomatic treatment of carcinoid tumors are somatostatin analogues; in addition to their beneficial effect on clinical symptoms they may stabilize tumor growth for many years and, less frequently, may produce tumor regression. The use of chemotherapeutic agents is considered in patients with aggressive, rapidly growing and advanced tumors; initial findings with temozolomide and thalidomide in clinical trials raise the possibility that these chemotherapeutic agents may prove to be new therapeutic options. Radioisotope-labeled peptide receptor therapy with 131 I-MIBG, 90 Y-DOTA-TOC or 177 Lu-DOTA-TOC may offer a highly effective option for patients with progressive and advanced stage of neuroendocrine tumors. Initial observations obtained in clinical trials with some tyrosine kinase inhibitors, antibodies against tyrosine kinases, and with inhibitors of mammalian target of rapamycin (mTOR) support the possibility that at least some of these new agents may have a role in future treatment options in patients with advanced neuroendocrine tumors.
 ...
PMID:[Carcinoid tumors]. 2104 39

The new positron emission tomography (PET/CT) methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1) somatostatin analogues labeled with indium-111 (111In-pentetreotide) or technetium-99m (99mTc-EDDA/HYNIC-TOC); 2) noradrenaline analogue labeled with iodine-131 or -123 (131/123I-MIBG); or 3) 99mTc(V)-DMSA. Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor imaging, after intravenous injection of pharmaceuticals labeled with positron emitters [fluorine-18 (18F), galium-68 (68Ga), or carbon-11 (11C)]: 1) glucose analogue (18FDG); 2) somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga-DOTANOC); 3) aminoacid precursors of bioamines: [a) dopamine precursor 18F-DOPA (6-18F-dihydroxyphenylalanine), b) serotonin precursor 11C-5HTP (11C-5-hydroxytryptophan)]; or 4) dopamine analogue 18F-DA (6-18F-fluorodopamine). Conventional and contemporary (PET/ CT) somatostatin receptor detection showed identical high spe- cificity (92%), but conventional had very low sensitivity (52%) compared to PET/CT (97%). It means that almost every second neuroendocrine tumor detected by contemporary method cannot be discovered using conventional (classic) method. In metastatic pheochromocytoma detection contemporary (PET/ CT) methods (18F-DOPA and 18F-DA) have higher sensitivity than conventional (131I/123I-MIBG). In medullary thyroid carcinoma diagnostics contemporary method ([18F-DOPA) is more sensitive than conventional 99mTc(V)-DMSA method, and is similar to 18FDG, computed tomography and magnetic resonance. In carcinoid detection contemporary method (18F-DOPA) shows similar results with contemporary somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine tumors it is worse. To conclude, contemporary (PET/CT) methods for somatostatin receptor detection (68Ga-DOTATOC/-NOC/-TATE) in neuroendocrine tumors are much more sensitive (almost twice) and more accurate than conventional. Therefore the classical methods should be urgently replaced by contemporary methods.
 ...
PMID:[Contemporary nuclear medicine diagnostics of neuroendocrine tumors]. 2584 63

The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor
 ...
PMID:Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report. 2643 42

The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium ((177)Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with (177)Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites of metastases included the liver (n = 5), breast (n = 1), and aortocaval nodes (n = 1). On baseline diagnostic study [(68) Ga-DOTANOC/TATE or the technetium ((99m)Tc)-hydrazinonicotinamide (HYNIC)-tektrotyd (TOC)], tracer uptake in the bone marrow in all patients was Grade III. At the time of analysis, the patients received three to four cycles of PRRT and a cumulative dose of 16.1-25.6 GBq with a follow-up duration ranging 10-27 months. The response as assessed by three parameters: (i) Symptomatic: All patients (except for one) reported excellent symptomatic palliation and better quality of life with improvement of Karnofsky/Lansky scores; the single case with nonresponse had shown symptomatic response in the initial 6 months following which he had a progressive disease and death at 18 months (ii) biochemical: Three patients had shown more than 50% reduction in the serum chromogranin level, one had shown increase but had demonstrated clinical evidence of response with radiologically stable disease while the other who had shown slight increase of chromogranin A (CgA) level had shown progressive disease thereafter (iii) radiological: Three patients demonstrated partial response (on FDG-PET/CT), one patient had stable disease and one patient had progressive disease following initial clinical response. As per the NCI-CTCAE score, only one patient had persistent Grade I anemia without any deterioration with the administered dose at the time of analysis. FDG uptake in the bone marrow metastatic lesions showed no obvious FDG avidity on visual assessment except for two patients (low-grade FDG uptake). Interestingly, the associated metastatic lesions [except for patient I with Mib1 labeling index (LI): 1-2%], demonstrated high FDG avidity. Thus, we observed that the majority (in our series four out of five patients, i.e. 80%) of the patients had excellent symptomatic response with at least stabilization of the disease at a follow-up period of 10-27 months. The single patient who had a progressive disease also had a good symptomatic response in the initial 6 months from the first dose of PRRT. Despite the extensive bone marrow involvement, no hematological toxicity was observed (only one patient showed Grade I anemia), suggesting that PRRT is well-tolerated by this particular subgroup.
...
PMID:Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with (177)Lu-DOTATATE. 2691 77


1 2 Next >>