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Journal of Pain and Symptom Management Aug 1994Octreotide, an analogue of somatostatin with a more favorable pharmacokinetic profile, is a new drug that may offer some advantages in the palliative care setting. It... (Review)
Review
Octreotide, an analogue of somatostatin with a more favorable pharmacokinetic profile, is a new drug that may offer some advantages in the palliative care setting. It has been used with favorable results in the management of some gastrointestinal disorders, such as gastrointestinal hemorrhage, diarrhea, short-bowel syndrome, fistula, and intestinal occlusion in the palliative care setting. These favorable results occurred without important side effects, underlining the potential role of this drug. The cost-benefit ratio of this expensive drug must be considered, however.
Topics: Gastrointestinal Diseases; Humans; Octreotide; Palliative Care
PubMed: 7525789
DOI: 10.1016/0885-3924(94)90178-3 -
Biomolecules Jul 2021By using solid targets in medical cyclotrons, it is possible to produce large amounts of GaCl. Purification of Ga from metal ion impurities is a critical step, as these...
By using solid targets in medical cyclotrons, it is possible to produce large amounts of GaCl. Purification of Ga from metal ion impurities is a critical step, as these metals compete with Ga in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting GaClcould be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. GaCl was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The GaCleluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [Ga]Ga-DOTATOC and [Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.
Topics: Acetates; Ascorbic Acid; Chelating Agents; Cyclotrons; Ethylenediamines; Gallium; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Isotope Labeling; Octreotide; Positron-Emission Tomography; Quinolines; Radiochemistry
PubMed: 34439784
DOI: 10.3390/biom11081118 -
Journal of Nuclear Medicine : Official... May 1999Scintigraphy with [111In-diethylenetriamine pentaacetic acid0-D-Phe1]-octreotide (DTPAOC) is used to demonstrate neuroendocrine and other somatostatin-receptor-positive... (Comparative Study)
Comparative Study
UNLABELLED
Scintigraphy with [111In-diethylenetriamine pentaacetic acid0-D-Phe1]-octreotide (DTPAOC) is used to demonstrate neuroendocrine and other somatostatin-receptor-positive tumors. Despite encouraging results, this 111In-labeled compound is not well suited for peptide-receptor-mediated radiotherapy of somatostatin-receptor-positive tumors. Another somatostatin analog, [1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid0, D-Phe1, Tyr3]-octreotide (DOTATOC), can be labeled with the beta-emitter 90Y in a stable manner.
METHODS
We compared the distribution, kinetics and dosimetry of 111In-DTPAOC and 111In-DOTATOC in eight patients to predict the outcomes of these parameters in patients who will be treated with 90Y-DOTATOC.
RESULTS
Serum radioactivity levels for the radiopharmaceuticals did not differ significantly 2-24 h after injection (P>0.05). Up to 2 h postinjection they were slightly, but significantly, lower after administration of 111In-DOTATOC (P < 0.01 at most time points). The percentage of peptide-bound radioactivity in serum did not differ after administration of either compound. Urinary excretion was significantly lower after administration of 111In-DOTATOC (P < 0.01). The visualization of known somatostatin-receptor-positive organs and tumors was clearer after administration of 111In-DOTATOC than after administration of 111In-DTPAOC. This was confirmed by significantly higher calculated uptakes in the pituitary gland and spleen. The uptake in the tumor sites did not differ significantly (P > 0.05), although in three of the four patients in whom tumor uptake could be calculated, it was higher after administration of 111In-DOTATOC.
CONCLUSION
The distribution and excretion pattern of 111In-DOTATOC resembles that of 111In-DTPAOC, and the uptake in somatostatin-receptor-positive organs and most tumors is higher for 111In-DOTATOC. If 90Y-DOTATOC shows an uptake pattern similar to 111In-DOTATOC, it is a promising radiopharmaceutical for peptide-receptor-mediated radiotherapy in patients with somatostatin-receptor-positive tumors.
Topics: Adult; Aged; Female; Humans; Indium Radioisotopes; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Radiation Dosage; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Tissue Distribution; Yttrium Radioisotopes
PubMed: 10319747
DOI: No ID Found -
European Journal of Nuclear Medicine... Mar 2024The lead-203 (Pb)/lead-212 (Pb) elementally identical radionuclide pair has gained significant interest in the field of image-guided targeted alpha-particle therapy for...
PURPOSE
The lead-203 (Pb)/lead-212 (Pb) elementally identical radionuclide pair has gained significant interest in the field of image-guided targeted alpha-particle therapy for cancer. Emerging evidence suggests that Pb-labeled peptide-based radiopharmaceuticals targeting somatostatin receptor subtype 2 (SSTR2) may provide improved effectiveness compared to beta-particle-based therapies for neuroendocrine tumors (NETs). This study aims to improve the performance of SSTR2-targeted radionuclide imaging and therapy through structural modifications to Tyr-octreotide (TOC)-based radiopharmaceuticals.
METHODS
New SSTR2-targeted peptides were designed and synthesized with the goal of optimizing the incorporation of Pb isotopes through the use of a modified cyclization technique; the introduction of a Pb-specific chelator (PSC); and the insertion of polyethylene glycol (PEG) linkers. The binding affinity of the peptides and the cellular uptake of Pb-labeled peptides were evaluated using pancreatic AR42J (SSTR2+) tumor cells and the biodistribution and imaging of the Pb-labeled peptides were assessed in an AR42J tumor xenograft mouse model. A lead peptide was identified (i.e., PSC-PEG-TOC), which was then further evaluated for efficacy in Pb therapy studies.
RESULTS
The lead radiopeptide drug conjugate (RPDC) - [Pb]Pb-PSC-PEG-TOC - significantly improved the tumor-targeting properties, including receptor binding and tumor accumulation and retention as compared to [Pb]Pb-DOTA-Tyr-octreotide (DOTATOC). Additionally, the modified RPDC exhibited faster renal clearance than the DOTATOC counterpart. These advantageous characteristics of [Pb]Pb-PSC-PEG-TOC resulted in a dose-dependent therapeutic effect with minimal signs of toxicity in the AR42J xenograft model. Fractionated administrations of 3.7 MBq [Pb]Pb-PSC-PEG-TOC over three doses further improved anti-tumor effectiveness, resulting in 80% survival (70% complete response) over 120 days in the mouse model.
CONCLUSION
Structural modifications to chelator and linker compositions improved tumor targeting and pharmacokinetics (PK) of Pb peptide-based radiopharmaceuticals for NET theranostics. These findings suggest that PSC-PEG-TOC is a promising candidate for Pb-based targeted radionuclide therapy for NETs and other types of cancers that express SSTR2.
Topics: Mice; Humans; Animals; Octreotide; Neuroendocrine Tumors; Radiopharmaceuticals; Tissue Distribution; Lead; Lead Radioisotopes; Receptors, Somatostatin; Chelating Agents
PubMed: 37955792
DOI: 10.1007/s00259-023-06494-9 -
European Journal of Nuclear Medicine... Aug 2023Peptide Receptor Radionuclide Therapy (PRRT) delivers targeted radiation to Somatostatin Receptor (SSR) expressing Neuroendocrine Neoplasms (NEN). We sought to assess...
UNLABELLED
Peptide Receptor Radionuclide Therapy (PRRT) delivers targeted radiation to Somatostatin Receptor (SSR) expressing Neuroendocrine Neoplasms (NEN). We sought to assess the predictive and prognostic implications of tumour dosimetry with respect to response by Ga DOTATATE (GaTate) PET/CT molecular imaging tumour volume of SSR (MITV) change and RECIST 1.1, and overall survival (OS).
METHODS
Patients with gastro-entero-pancreatic (GEP) NEN who received LuTate followed by quantitative SPECT/CT (Q-SPECT/CT) the next day (Jul 2010 to Jan 2019) were retrospectively reviewed. Single time-point (STP) lesional dosimetry was performed for each cycle using population-based pharmacokinetic modelling. MITV and RECIST 1.1 were measured at 3-months post PRRT.
RESULTS
Median of 4 PRRT cycles were administered to 90 patients (range 2-5 cycles; mean 27.4 GBq cumulative activity; mean 7.6 GBq per cycle). 68% received at least one cycle with radiosensitising chemotherapy (RSC). RECIST 1.1 partial response was 24%, with 70% stable and 7% progressive disease. Cycle 1 radiation dose in measurable lesions was associated with local response (odds ratio 1.5 per 50 Gy [95% CI: 1.1-2.0], p = 0.002) when adjusted by tumour grade and RSC. Median change in MITV was -63% (interquartile range -84 to -29), with no correlation with radiation dose to the most avid lesion on univariable or multivariant analyses (5.6 per 10 Gy [95% CI: -1.6, 12.8], p = 0.133). OS at 5-years was 68% (95% CI: 56-78%). Neither baseline MITV (hazard ratio 1.1 [95% CI: 1.0, 1.2], p = 0.128) nor change in baseline MITV (hazard ratio 1.0 [95% CI: 1.0, 1.1], p = 0.223) were associated with OS when adjusted by tumour grade and RSC but RSC was (95% CI: 0.2, 0.8, p = 0.012).
CONCLUSION
Radiation dose to tumour during PRRT was predictive of radiologic response but not survival. Survival outcomes may relate to other biological factors. There was no evidence that MITV change was associated with OS, but a larger study is needed.
Topics: Humans; Positron Emission Tomography Computed Tomography; Retrospective Studies; Positron-Emission Tomography; Neuroendocrine Tumors; Organometallic Compounds; Pancreatic Neoplasms; Octreotide
PubMed: 37184682
DOI: 10.1007/s00259-023-06257-6 -
Asian Journal of Surgery Feb 2019Octreotide is known to decrease the rate of postoperative complication after pancreatic resection by diminishing exocrine function of the pancreas. The aim of this study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Octreotide is known to decrease the rate of postoperative complication after pancreatic resection by diminishing exocrine function of the pancreas. The aim of this study was to evaluate the effect of octreotide in decreasing exocrine excretion of pancreas and preventing pancreatic fistula.
MATERIALS AND METHODS
Prospective randomized trial was conducted involving 59 patients undergoing pancreaticoduodenectomy for either malignant or benign tumor, 29 patients were randomized to receive octreotide; 30 patients allotted to placebo. All pancreaticojejunal anastomosis was performed with external stent of negative-pressured drainage and the amount of pancreatic juice through the external stent was measured until postoperative 7th day. Pancreatic fistula was recorded.
RESULTS
There were no differences in demographics, pancreatic texture and pancreatic duct diameter between the octreotide and placebo group. The median output of pancreatic juice was not significantly different between both groups during 7 days after surgery. When the patients were stratified according to the diameter of pancreatic duct (duct ≤5 mm, > 5 mm), there were no significant differences in daily amount of pancreatic juice, however, when stratified according to pancreatic texture, median output of pancreatic juice was significantly lower in patients with hard pancreas compared with those with soft pancreas from 5 day to 7 day after surgery (p < 0.05). No significant differences in pancreatic fistula and postoperative complications were found between the octreotide and placebo groups.
CONCLUSIONS
Prophylactic octreotide is not effective to inhibit the exocrine secretion of the remnant pancreas and does not decrease the incidence of pancreatic fistula after pancreaticoduodenectomy.
Topics: Aged; Aged, 80 and over; Biomarkers; Drug Administration Schedule; Female; Follow-Up Studies; Gastrointestinal Agents; Humans; Male; Middle Aged; Octreotide; Pancreas, Exocrine; Pancreatic Fistula; Pancreatic Juice; Pancreaticoduodenectomy; Pancreaticojejunostomy; Postoperative Complications; Prospective Studies; Treatment Outcome
PubMed: 30262436
DOI: 10.1016/j.asjsur.2018.08.006 -
British Journal of Cancer Jun 2007
Clinical Trial
Topics: Antineoplastic Agents, Hormonal; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Octreotide; Receptors, Somatostatin
PubMed: 17505506
DOI: 10.1038/sj.bjc.6603799 -
Journal of Pediatric Gastroenterology... Dec 2015The aim of the present study was to study the effect of octreotide on colonic motility in pediatric patients with recalcitrant chronic constipation/encopresis and other... (Clinical Trial)
Clinical Trial
OBJECTIVE
The aim of the present study was to study the effect of octreotide on colonic motility in pediatric patients with recalcitrant chronic constipation/encopresis and other suspected colonic motility disorders.
METHODS
This was a nonrandomized, single-center, open-label, prospective study evaluating the effect of a single subcutaneous dose of octreotide on colonic motility.
RESULTS
Thirteen patients (5 boys) were enrolled in the study. The age range was 4.6 to 16.2 years. Eleven patients (84%) had normal colonic manometry and 2 patients (16%) had colonic neuropathy. Motility Index (MI) (mmHg) for the 15 minutes before and after octreotide infusion was 6.03 ± 1.26 (95% confidence interval [CI] 5.35-6.72) and 5.32 ± 1.66 (95% CI 4.42-6.23), respectively, with P value of 0.08. MI for the 30 minutes before and after octreotide infusion was 6.89 ± 1.37 (95% CI 6.14-7.64) and 6.71 ± 1.47 (95% CI 5.91-7.52), respectively, with P value of 0.55. MI for the 45 minutes before and after octreotide infusion was 7.73 ± 1.32 (95% CI 7.01-8.45) and 7.53 ± 1.38 (95% CI 6.78-8.28), respectively, with P value of 0.8.
CONCLUSION
Our study showed that the administration of octreotide resulted in no significant changes in colonic MI in pediatric patients with chronic recalcitrant constipation.
Topics: Adolescent; Child; Child, Preschool; Colon; Colonic Diseases; Constipation; Encopresis; Fecal Incontinence; Female; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Male; Manometry; Octreotide; Prospective Studies
PubMed: 26595852
DOI: 10.1097/MPG.0000000000000872 -
Journal of Nuclear Medicine : Official... Apr 2019Peptide receptor radionuclide therapy (PRRT) has been used for more than 20 y as a systemic treatment approach in inoperable or metastatic somatostatin receptor-positive...
Peptide receptor radionuclide therapy (PRRT) has been used for more than 20 y as a systemic treatment approach in inoperable or metastatic somatostatin receptor-positive tumors. The purpose of this study was to analyze the long-term outcome of PRRT with regard to the most commonly used radiopharmaceuticals, Y-DOTATOC and Lu-DOTATATE. This retrospective clinical study included a total of 44 consecutive patients (27 men) with advanced tumors and enhanced somatostatin receptor expression. Mean age at initial diagnosis was 60 y (SD, 11.3 y; range, 40-84 y). Median follow-up was 80 mo. For Lu-PRRT, the mean number of cycles administered was 5.3 ± 2.5 and the mean activity was 27.2 ± 14.9 GBq per patient. For Y-PRRT, the mean number of cycles administered was 5.5 ± 2.6 and the mean activity was 14.7 ± 7.3 GBq per patient. Overall, 378 cycles were administered (mean, 8.6 ± 3.4 cycles per patient), with an overall cumulative activity of 1,514.1 GBq. Median overall survival was 79 mo. Twenty-one (77.8%) of the 27 men and 9 (52.9%) of the 17 women had died 12 y after commencement of PRRT. The shortest duration of illness was 8 mo and the longest 155 mo. Severe side effects (World Health Organization grades III and IV) were seen in 9 of the 14 patients still alive. Chronic kidney disease in combination with anemia was the most common finding in the 9 patients with severe side effects. A poor prognosis was found for those patients who showed progressive disease, in comparison with patients with cumulative disease control after initial PRRT (log rank, < 0.001), whereas women and patients with no more than 2 tumor sites seemed to especially benefit from PRRT (not reaching significance levels). PRRT is encouraging in terms of long-term outcome. Thirty-two percent (14/44 patients) of the patients with metastatic or inoperable disease were still alive more than 12 y after the beginning of radionuclide therapy. Possible predictors for favorable outcome are having an initial response to PRRT, having a low number of affected sites, and being female.
Topics: Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Octreotide; Receptors, Peptide; Receptors, Somatostatin; Retrospective Studies; Survival Analysis; Treatment Outcome
PubMed: 30115690
DOI: 10.2967/jnumed.118.215376 -
HPB : the Official Journal of the... Oct 2014
Topics: Humans; Octreotide; Pancreatic Fistula; Pancreaticoduodenectomy
PubMed: 25209611
DOI: 10.1111/hpb.12304