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Journal of Nuclear Medicine : Official... Dec 1995Copper-64 (T1/2 = 12.8 hr) is a reactor-produced radionuclide that has applications in both nuclear medicine imaging by PET and radiotherapy. Octreotide, a somatostatin... (Comparative Study)
Comparative Study
UNLABELLED
Copper-64 (T1/2 = 12.8 hr) is a reactor-produced radionuclide that has applications in both nuclear medicine imaging by PET and radiotherapy. Octreotide, a somatostatin receptor ligand, has been conjugated with TETA and CPTA, labeled with 64Cu, evaluated both in vitro and in vivo and compared to 111In-DTPA-D-Phe1-octreotide.
METHODS
The carboxylic acid moieties on the T bifunctional chelates were conjugated to the N-terminal amine of D-Phe using the linking agents hydroxybenzotriazol (HOBT) and diisopropylcarbodiimide (DIC). Receptor binding assays on all three radiolabeled octreotide conjugates were accomplished in AtT20 mouse pituitary carcinoma cell membranes. In vivo biodistribution was performed using normal Sprague-Dawley rats and Lewis rats carrying a somatostatin receptor-positive rat pancreatic tumor.
RESULTS
The binding affinities of 64Cu-CPTA-D-Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide in AtT20 cell membranes were both greater than 111In-DTPA-D-Phe1-octreotide (Kd, 78.5 pM, 314 pM and 3.28 nM, respectively). In normal rats, 64Cu-CPTA-D-Phe1-octreotide was localized primarily in the liver. Copper-64-TETA-D-Phe1-octreotide, similar to 111In-DTPA-D-Phe1-octreotide, had moderate uptake in the kidneys; the hepatobiliary uptake was negligible. In rats bearing CA 20948 pancreatic tumors, both 64Cu-CPTA-D-Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide had uptake in tumors comparable to better than 111In-DTPA-D-Phe1-octreotide.
CONCLUSION
Of the two 64Cu-labeled octreotide conjugates evaluated, 64Cu-CPTA-D-Phe1-octreotide has the highest affinity for the somatostatin receptor; however, the clearance was hepatobiliary with slow excretion. Copper-64-TETA-D-Phe1-octreotide binds to the somatostatin receptor with five times the affinity of 111In-octreotide, has desirable clearance properties (renal clearance with rapid excretion) and is a potential agent for PET imaging of somatostatin receptors.
Topics: Adrenal Glands; Animals; Copper Radioisotopes; Female; Indium Radioisotopes; Male; Mice; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Pituitary Neoplasms; Rats; Rats, Inbred Lew; Rats, Sprague-Dawley; Receptors, Somatostatin; Tissue Distribution; Tomography, Emission-Computed; Tumor Cells, Cultured
PubMed: 8523125
DOI: No ID Found -
BioMed Research International 2023Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the...
BACKGROUND
Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion.
METHODS
Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation.
RESULTS
The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups.
CONCLUSION
Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.
Topics: Male; Animals; Rats; Pantoprazole; Gastrins; Alkaline Phosphatase; Octreotide; Bone Diseases, Metabolic; Parathyroid Hormone
PubMed: 37711876
DOI: 10.1155/2023/2594664 -
Internal Medicine (Tokyo, Japan) Oct 1994A somatostatin analogue (SMS-201-995, hereinafter "octreotide") was s.c. administered to 5 healthy subjects under consecutive dripping of CCK-PZ...
A somatostatin analogue (SMS-201-995, hereinafter "octreotide") was s.c. administered to 5 healthy subjects under consecutive dripping of CCK-PZ (cholecystokinin-pancreozymin) and secretin (0.01 CHR U/kg/minutes), after inserting a Dreiling double tube into Treitz's ligament. Bile acid concentration, and bicarbonate and lipase excretions in duodenal juice were determined every 10 minutes up to 120 minutes and compared with controls. Moreover, octreotide (100 micrograms) was s.c. administered to 5 healthy subjects 30 minutes before meals for 7 days. Fecal fat and bile acid excretions before and after administration were determined. Bile acid concentration, and bicarbonate and lipase excretions in the octreotide group decreased to 1/3-1/4 that of controls. Bile acid concentration became 0 mM for 60 minutes. Fecal fat excretion increased; obvious steatorrhea occurred in 2 cases. Fecal bile acid excretion decreased to about 1/4. These results suggest that decreases in bile acid secretion should be considered, as well as pancreatic lipase and bicarbonate secretions, when fatty stool occurs after octreotide administration.
Topics: Adult; Bicarbonates; Bile Acids and Salts; Celiac Disease; Dietary Fats; Duodenum; Humans; Intestinal Secretions; Lipase; Male; Octreotide; Pancreas; Time Factors
PubMed: 7827373
DOI: 10.2169/internalmedicine.33.593 -
Antioxidants & Redox Signaling May 2019Peptide receptor radionuclide therapy (PRRT) is in clinical use today to treat metastatic neuroendocrine tumors. Infused, radiolabeled, somatostatin analog peptides... (Review)
Review
AIMS
Peptide receptor radionuclide therapy (PRRT) is in clinical use today to treat metastatic neuroendocrine tumors. Infused, radiolabeled, somatostatin analog peptides target tumors that are killed by irradiation damage. The peptides, however, are also retained in kidneys due to glomerular filtration, and the administered doses must be limited to avoid kidney damage. The human radical scavenger and antioxidant, α-microglobulin (A1M), has previously been shown to protect bystander tissue against irradiation damage and has pharmacokinetic and biodistribution properties similar to somatostatin analogs. In this study, we have investigated if A1M can be used as a renal protective agent in PRRT.
RESULTS
We describe nephroprotective effects of human recombinant A1M on the short- and long-term renal damage observed following lutetium 177 (Lu)-DOTATATE (150 MBq) exposure in BALB/c mice. After 1, 4, and 8 days (short term), Lu-DOTATATE injections resulted in increased formation of DNA double-strand breaks in the renal cortex, upregulated expression of apoptosis and stress response-related genes, and proteinuria (albumin in urine), all of which were significantly suppressed by coadministration of A1M (7 mg/kg). After 6, 12, and 24 weeks (long term), Lu-DOTATATE injections resulted in increased animal death, kidney lesions, glomerular loss, upregulation of stress genes, proteinuria, and plasma markers of reduced kidney function, all of which were suppressed by coadministration of A1M. Innovation and Conclusion: This study demonstrates that A1M effectively inhibits radiation-induced renal damage. The findings suggest that A1M may be used as a radioprotector during clinical PRRT, potentially facilitating improved tumor control and enabling more patients to receive treatment.
Topics: Alpha-Globulins; Animals; Antioxidants; Biomarkers; Gene Expression Profiling; Histones; Humans; Kidney; Mice; Models, Animal; Octreotide; Organometallic Compounds; Radiation-Protective Agents; Survival Rate; Time Factors
PubMed: 29943622
DOI: 10.1089/ars.2018.7517 -
Drug Delivery Dec 2021The purpose of this study was to optimize the preparation method of injectable Octreotide microspheres. To explore the correlation between the solvent system and the...
The purpose of this study was to optimize the preparation method of injectable Octreotide microspheres. To explore the correlation between the solvent system and the general properties of microspheres to reduce burst release and enable them to be used for portal hypertension. Octreotide microspheres were prepared by modified double emulsion solution evaporation method after optimizing preparation conditions. The results showed that Octreotide microspheres had a particle size of 57.48 ± 15.24 μm, and the initial release was significantly reduced. In vitro release and in vivo pharmacokinetic data indicated that Octreotide was released stably within 1200 h. The effects on portal vein pressure, liver tissue morphology and other related indexes were observed after administration. As obvious results, injection of Octreotide microspheres could significantly reduce portal vein pressure and reduce the portal vein lumen area in experimental cirrhotic portal hypertensive rats. The optimized Octreotide PLGA microsphere preparation has been proved to have a good effect on PHT in vivo after detecting aminotransferase (AST) and alanine aminotransferase (ALT) activity, liver tissue hydroxyproline (Hyp) content, serum and liver tissue malondialdehyde (MDA) levels, plasma prostacyclin (PGI) levels, and liver tissue tumor necrosis factor (TNFα) content. In addition, serum and liver tissue superoxide dismutase (SOD) activity and liver tissue glutathione (GSH) content, plasma thromboxane (TXA), serum nitric oxide (NO), liver tissue nitric oxide synthase (NOS), and plasma and liver tissue endothelin (ET) were significantly increased.
Topics: Animals; Antineoplastic Agents, Hormonal; Chemistry, Pharmaceutical; Drug Carriers; Hypertension, Portal; Liver Function Tests; Male; Microspheres; Octreotide; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Wistar
PubMed: 33825592
DOI: 10.1080/10717544.2021.1898702 -
European Journal of Nuclear Medicine... Jul 2015Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in...
PURPOSE
Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor.
METHODS
Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving (90)Y-DOTATOC, (177)Lu-DOTATOC or their combination.
RESULTS
(90)Y-DOTATOC plus (177)Lu-DOTATOC treatment was associated with longer survival than (90)Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or (177)Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). (177)Lu-DOTATOC was associated with longer survival than (90)Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). (90)Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5% vs. 4.0%, p = 0.005) or (177)Lu-DOTATOC (9.5 vs. 1.4%, p = 0.002). Renal toxicity was similar among the treatments.
CONCLUSIONS
Using (90)Y and (177)Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Radiopharmaceuticals; Survival Analysis
PubMed: 25792454
DOI: 10.1007/s00259-015-3030-9 -
Journal of Nuclear Medicine : Official... Jun 2000In this paper we describe the preclinical evaluation of 99mTc-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) using different coligands for radiolabeling and a comparison... (Comparative Study)
Comparative Study
UNLABELLED
In this paper we describe the preclinical evaluation of 99mTc-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) using different coligands for radiolabeling and a comparison of their in vitro and in vivo properties with 111In-diethylenetriaminepentaacetic acid (DTPA)-octreotide.
METHODS
HYNIC-TOC was radiolabeled at high specific activities using tricine, ethylenediaminediacetic acid (EDDA), and tricine-nicotinic acid as coligand systems. Receptor binding was tested using AR42J rat pancreatic tumor cell membranes. Internalization and protein binding studies were performed, and biodistribution and tumor uptake were determined in AR42J tumor-bearing nude mice.
RESULTS
All 99mTc-labeled HYNIC peptides showed retained somatostatin-receptor binding affinities (Kd < 2.65 nM). Protein binding and internalization rates were dependent on the coligand used. Specific tumor uptake between 5.8 and 9.6 percentage injected dose per gram (%ID/g) was found for the 99mTc-labeled peptides, compared with 4.3 %ID/g for 111In-DTPA-octreotide. Tricine as coligand showed higher activity levels in muscle, blood, and liver, whereas tricine-nicotinic acid produced significant levels of activity in the gastrointestinal tract. EDDA showed the most promising overall biodistribution profile, with tumor-to-liver and tumor-to-gastrointestinal tract ratios similar to those obtained with 111In-DTPA-octreotide, lower ratios in blood and muscle, but considerably higher tumor-to-kidney ratios.
CONCLUSION
TOC can be radiolabeled to high specific activities using HYNIC as a bifunctional chelator. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make 99mTc-EDDA-HYNIC-TOC a promising candidate for an alternative to 111In-DTPA-octreotide for tumor imaging.
Topics: Animals; Indium Radioisotopes; Mice; Mice, Nude; Neoplasm Transplantation; Octreotide; Organotechnetium Compounds; Pancreatic Neoplasms; Radionuclide Imaging; Receptors, Somatostatin; Tissue Distribution; Tumor Cells, Cultured
PubMed: 10855644
DOI: No ID Found -
Bulletin Du Cancer Feb 2012This phase II, multicenter, randomized, double-blind, non-comparative study assessed the efficacy and safety of immediate-release octreotide and octreotide LAR, in... (Randomized Controlled Trial)
Randomized Controlled Trial
This phase II, multicenter, randomized, double-blind, non-comparative study assessed the efficacy and safety of immediate-release octreotide and octreotide LAR, in combination with corticosteroids and standard medical care, on the symptoms of inoperable malignant bowel obstruction (MBO) due to peritoneal carcinomatosis. The primary efficacy endpoint was "success" at day 14 defined as a composite endpoint including the absence of a nasogastric tube, and vomiting less than twice per day and no use of anticholinergic agents. Patients in the octreotide arm received octreotide LAR 30 mg intramuscular (im) on days 1, 29 and 57, as well as daily immediate-release octreotide 600 μg per day plus methylprednisolone on days 1 to 6. Placebo-treated patients received methylprednisolone and matched placebo instead of octreotide. Difficulties associated with enrolling patients at palliative-care stage meant only 64 patients (instead of the planned 102 patients) were randomized, 32 to octreotide and 32 to placebo. Despite randomization, more patients in the octreotide arm (46.4%) than in the placebo arm (21.9%) had a baseline Karnofsky score less than 50. An intention-to-treat analysis showed that in the octreotide and placebo arms, 12 (38%) and nine (28%), respectively, patients were successfully treated at day 14, which increased to 9/15 (60%) and 7/25 (28%), respectively, among patients with a baseline Karnofsky score greater or equal to 50. Octreotide-treated patients reported three drug-related adverse events (AEs), and no drug-related serious AEs or deaths. Octreotide LAR may have a key role in treating patients with a MBO due to peritoneal carcinomatosis, particularly in those with moderately severe disease.
Topics: Aged; Antiemetics; Carcinoma; Device Removal; Double-Blind Method; Drug Therapy, Combination; Female; France; Gastrointestinal Agents; Humans; Intestinal Obstruction; Intubation, Gastrointestinal; Karnofsky Performance Status; Male; Methylprednisolone; Middle Aged; Octreotide; Peritoneal Neoplasms; Pilot Projects; Vomiting
PubMed: 22265994
DOI: 10.1684/bdc.2011.1535 -
JCO Oncology Practice Sep 2022Somatostatin analogs octreotide long-acting release (octLAR) and lanreotide are equally acceptable in National Comprehensive Cancer Network guidelines for neuroendocrine... (Randomized Controlled Trial)
Randomized Controlled Trial
A Randomized Trial Evaluating Patient Experience and Preference Between Octreotide Long-Acting Release and Lanreotide for Treatment of Well-Differentiated Neuroendocrine Tumors.
PURPOSE
Somatostatin analogs octreotide long-acting release (octLAR) and lanreotide are equally acceptable in National Comprehensive Cancer Network guidelines for neuroendocrine tumors (NETs). Lanreotide is more expensive and given by deep subcutaneous injection, whereas octLAR is given intramuscularly. We evaluated patient preference between these agents in terms of injection site pain.
MATERIALS AND METHODS
Randomized, single-blinded study. Patients with NETs received injections every 4 weeks. Arm 1: octLAR × 3, then lanreotide × 3; arm 2: reverse order. Self-reported injection site pain scores (range, 0-10) were obtained after each of the first three injections. Primary end point was comparison of mean pain scores over the first three injections. Secondary end points included patient-reported preference.
RESULTS
Fifty-one patients enrolled (26 in arm 1 and 25 arm 2), all evaluable for primary end point. No significant difference was identified in the mean pain score over the first three injections (2.4 ± 1.9 1.9 ± 1.5, = .5). Thirty-four of 51 (67%) patients (15 in arm 1 and 19 in arm 2) completed post-therapy questionnaires and were evaluable for secondary end points. Seven patients (47%) in arm 1 and eight patients (42%) in arm 2 indicated no drug preference at the end of treatment. In the other 19 patients, more patients indicated mild or strong preference for octLAR over lanreotide.
CONCLUSION
We found minimal pain with octLAR and lanreotide and no significant pain score differences between the two. Patients indicating a drug preference trended toward favoring octLAR.
Topics: Humans; Neuroendocrine Tumors; Octreotide; Pain; Patient Outcome Assessment; Peptides, Cyclic; Somatostatin
PubMed: 35724357
DOI: 10.1200/OP.22.00055 -
European Journal of Cardio-thoracic... Jan 2024Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the efficacy of octreotide remains unclear. A decrease in lymph production is suggested as the mechanism. In this cross-over study, we explore the direct effect of octreotide on human lymphatic drainage.
METHODS
Pre-clinical: the effect of octreotide on force generation was assessed during acute and prolonged drug incubation on human lymphatic vessels mounted in a myograph. Clinical: in a double-blinded, randomized, cross-over trial including 16 healthy adults, we administered either octreotide or saline as an intravenous infusion for 2.5 h. Near-infrared fluorescence imaging was used to examine spontaneous lymphatic contractions and lymph pressure in peripheral lymphatic vessels and plethysmography was performed to assess the capillary filtration rate, capillary filtration coefficient and isovolumetric pressures of the lower leg.
RESULTS
Pre-clinical: human thoracic duct (n = 12) contraction rate was concentration-dependently stimulated by octreotide with a maximum effect at 10 and 100 nmol/l in the myograph chamber. Clinical: spontaneous lymphatic contractions and lymph pressure evaluated by near-infrared fluorescence did not differ between octreotide or placebo (P = 0.36). Plethysmography revealed similar capillary filtration coefficients (P = 0.057), but almost a doubling of the isovolumetric pressures (P = 0.005) during octreotide infusion.
CONCLUSIONS
Octreotide stimulated lymphatic contractility in the pre-clinical setup but did not affect the spontaneous lymphatic contractions or lymph pressure in healthy individuals. Plethysmography revealed a doubling in the isovolumetric pressure. These results suggest that octreotide increases lymphatic drainage capacity in situations with high lymphatic afterload.
Topics: Adult; Humans; Octreotide; Chylothorax; Gastrointestinal Agents; Cross-Over Studies; Lymphatic Vessels
PubMed: 37951584
DOI: 10.1093/ejcts/ezad380