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Nuclear Medicine and Biology 2024DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors...
Investigation of imaging the somatostatin receptor by opening the blood-brain barrier with melittin - A feasibility study using positron emission tomography and [Cu]Cu-DOTATATE.
DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors are found naturally in the intestines, pancreas, lungs, and brain (mainly cortex). In vivo measurement of the somatostatin receptors in the cortex has been challenging because available tracers cannot cross the blood-brain barrier (BBB) due to their intrinsic polarity. A peptide called melittin, a main component of honeybee venom, has been shown to disrupt plasma membranes and increase the permeability of biological membranes. In this study, we assessed the feasibility of using melittin to facilitate the passage of [Cu]Cu-DOTATATE through the BBB and its binding to somatostatin receptors in the cortex. Evaluation included in vitro autoradiography on Long Evans rat brains to estimate the binding affinity of [Cu]Cu-DOTATATE to the somatostatin receptors in the cortex and an in vivo evaluation of [Cu]Cu-DOTATATE binding in NMRI mice after injection of melittin. This study found an in vitro B = 89 ± 4 nM and K = 4.5 ± 0.6 nM in the cortex, resulting in a theoretical binding potential (BP) calculated as B/K ≈ 20, which is believed suitable for in vivo brain PET imaging. However, the in vivo results showed no significant difference between the control and melittin injected mice, indicating that the honeybee venom failed to open the BBB. Additional experiments, potentially involving faster injection rates are required to verify that melittin can increase brain uptake of non-BBB permeable PET tracers. Furthermore, an evaluation of whether a venom with a narrow therapeutic range can be used for clinical purposes needs to be considered.
Topics: Animals; Receptors, Somatostatin; Melitten; Rats; Feasibility Studies; Positron-Emission Tomography; Organometallic Compounds; Blood-Brain Barrier; Male; Mice; Copper Radioisotopes; Octreotide
PubMed: 38555651
DOI: 10.1016/j.nucmedbio.2024.108905 -
Frontiers in Immunology 2024Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more...
Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering -emitting Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response. To determine the optimal dosage and timing of Lu-DOTATATE treatment, we measured CAR T cell infiltration and expansion in tumors longitudinally through positron emission tomography (PET) using a SSTR2-specific positron-emitting radiotracer,F-NOTA-Octreotide. In animals receiving CAR T cells and a low-dose (2.5 Gy) of TRT following the administration of Lu-DOTATATE, we observed a rapid regression of large subcutaneous tumors, which coincided with a dramatic increase in serum proinflammatory cytokines. Tumor burden was also reduced when a higher radiation dose (6 Gy) was delivered to the tumor. However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.
Topics: Animals; Neoplasms; Octreotide; T-Lymphocytes; Immunotherapy; Radioisotopes
PubMed: 38550578
DOI: 10.3389/fimmu.2024.1355388 -
Journal of Medical Case Reports Mar 2024Pancreaticopleural fistula is a rare complication of pancreatitis and poses diagnostic and therapeutic challenges. This case report sheds light on the unique challenges... (Review)
Review
BACKGROUND
Pancreaticopleural fistula is a rare complication of pancreatitis and poses diagnostic and therapeutic challenges. This case report sheds light on the unique challenges posed by pancreaticopleural fistula as a rare complication of pancreatitis. The aim is to contribute valuable insights to the scientific literature by presenting a case involving a middle-aged man with acute necrotizing pancreatitis and associated pleural effusion.
CASE PRESENTATION
A 41-year-old Asian male with a history of pancreatitis and chronic alcohol use presented with severe dyspnea, chest pain, and left-sided pleural effusion. Elevated serum amylase lipase levels and imaging confirmed acute necrotizing pancreatitis with a computed tomography severity index of 8/10. Magnetic resonance cholangiopancreatography revealed pancreatic necrosis and pseudocyst formation and findings suggestive of pancreaticopleural fistula. The patient was then treated with octreotide therapy.
CONCLUSION
The management of pancreaticopleural fistula demands a comprehensive and individualized approach. Recognition guided by high clinical suspicion coupled with appropriate investigations and a careful balance between medical, endoscopic, and surgical interventions is crucial for achieving favorable outcomes. This case report adds to the scientific literature by providing insights into the complexities of pancreaticopleural fistula and emphasizing the importance of personalized strategies in its management.
Topics: Adult; Humans; Male; Cholangiopancreatography, Endoscopic Retrograde; Pancreatic Fistula; Pancreatitis, Acute Necrotizing; Pleural Diseases; Pleural Effusion; Respiratory Tract Fistula
PubMed: 38549170
DOI: 10.1186/s13256-024-04457-8 -
Turk Gogus Kalp Damar Cerrahisi Dergisi Jan 2024Chylothoraces are mostly secondary to trauma and tumors, and rarely idiopathic. Chylothoraces secondary to lung tumors are mostly seen postoperatively. In this article,...
Chylothoraces are mostly secondary to trauma and tumors, and rarely idiopathic. Chylothoraces secondary to lung tumors are mostly seen postoperatively. In this article, we, for the first time, present massive chylothorax developing after diagnostic transthoracic Tru-cut biopsy in a lung adenocarcinoma case. The patient was successfully treated with drainage and octreotide. In conclusion, it should be kept in mind that chylothorax can be also seen as a complication after interventional biopsy procedures; therefore, the patients should be followed carefully.
PubMed: 38545351
DOI: 10.5606/tgkdc.dergisi.2024.22556 -
Current Oncology (Toronto, Ont.) Mar 2024Chylous ascites is a rare form of ascites with high triglyceride content arising from the thoracoabdominal lymph nodes in the peritoneal cavity due to various benign or...
Chylous ascites is a rare form of ascites with high triglyceride content arising from the thoracoabdominal lymph nodes in the peritoneal cavity due to various benign or malignant etiologies, including pancreatic cancer. During cancer chemotherapy, the accumulation of ascites can lead to the deterioration of the patient's general condition, making chemotherapy administration difficult, and resulting in a poor prognosis. We encountered a rare case of chylous ascites complicated by advanced pancreatic cancer. The patient presented with a discrepancy between the shrinkage of the pancreatic cancer and the accumulation of ascites. Therefore, we were able to promptly diagnose chylous ascites by performing biochemical tests. The patient was treated with octreotide, reportedly effective in treating chylous ascites, which rapidly improved the chylous ascites and general condition of the patient, allowing the patient to continue chemotherapy for pancreatic cancer. Therefore, physicians should consider the possibility of chylous ascites when clinically unexplained ascites are observed in patients with advanced cancer. The investigation and treatment of chylous ascites should be initiated as soon as possible.
Topics: Humans; Chylous Ascites; Ascites; Pancreatic Neoplasms; Octreotide; Lymph Nodes
PubMed: 38534945
DOI: 10.3390/curroncol31030112 -
Therapeutic Advances in Medical Oncology 2024Somatostatin analogs (SSA), specifically octreotide and lanreotide, have demonstrated antiproliferative effects in patients with neuroendocrine tumors (NET), a group of... (Review)
Review
Somatostatin analogs (SSA), specifically octreotide and lanreotide, have demonstrated antiproliferative effects in patients with neuroendocrine tumors (NET), a group of rare malignancies of diverse origin and presentation. A prominent feature of NET cells is the expression of G protein-coupled receptors called somatostatin receptors (SSTR). Although these SSTR are not uniformly present in NET, they can be instrumental in the diagnosis and treatment of NET. Apart from their application in nuclear imaging and radionuclide therapy, SSA have proven invaluable in the treatment of hormonal syndromes associated with certain NET (antisecretory effects of SSA), but it took more than two decades to convincingly demonstrate the antiproliferative effects of SSA in metastatic NET with the two pivotal studies PROMID and CLARINET. The current review summarizes three decades of SSA treatment and provides an overview of the clinical trial landscape for SSA monotherapy and combination therapy, including clinical implications and quality of life aspects, as well as ongoing fields of research.
PubMed: 38529270
DOI: 10.1177/17588359241240316 -
European Journal of Nuclear Medicine... Jul 2024To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [Lu]Lu-satoreotide tetraxetan in patients with advanced...
PURPOSE
To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs).
METHODS
This study was part of a phase I/II trial of [Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients.
RESULTS
In all evaluated organs, maximum [Lu]Lu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57-66% within 48 h following the first treatment cycle. At the first treatment cycle, [Lu]Lu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of [Lu]Lu-satoreotide tetraxetan were 5.0 Gy/GBq in tumours, 0.1 Gy/GBq in the bone marrow, 0.9 Gy/GBq in kidneys, 0.2 Gy/GBq in the liver and 0.8 Gy/GBq in the spleen. Using image-based dosimetry, the bone marrow and kidneys received median cumulative absorbed doses of 1.1 and 10.8 Gy, respectively, after three cycles.
CONCLUSION
[Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy.
TRIAL REGISTRATION
NCT02592707. Registered October 30, 2015.
Topics: Humans; Neuroendocrine Tumors; Male; Middle Aged; Female; Aged; Adult; Radiometry; Lutetium; Tissue Distribution; Somatostatin; Disease Progression; Radiopharmaceuticals; Aged, 80 and over; Octreotide; Radioisotopes
PubMed: 38528164
DOI: 10.1007/s00259-024-06682-1 -
ACG Case Reports Journal Mar 2024Chronic octreotide use has been associated with gallstone formation. Historically, cholecystectomy has been the defining treatment for those who have gallstone-related...
Chronic octreotide use has been associated with gallstone formation. Historically, cholecystectomy has been the defining treatment for those who have gallstone-related disease. For those who are poor surgical candidates, percutaneous and endoscopic approaches have been used. We describe the endoscopic management of a 74-year-old man with significant gallstone burden and associated sequelae because of chronic octreotide for metastatic neuroendocrine tumor through endoscopic ultrasound-guided cholecystoduodenostomy with gallstone extraction using lumen-apposing metal stents.
PubMed: 38524262
DOI: 10.14309/crj.0000000000001306 -
AACE Clinical Case Reports 2024To report a case of recalcitrant post-surgical hypocalcemia caused by hypoparathyroidism complicated by a chyle leak and octreotide use.
BACKGROUND/OBJECTIVE
To report a case of recalcitrant post-surgical hypocalcemia caused by hypoparathyroidism complicated by a chyle leak and octreotide use.
CASE REPORT
A man in his 60s with a 4-month history of voice changes, 10-pound weight loss, and a right-sided neck mass presented with difficulty breathing for 1 week. He had a right laryngeal/hypopharyngeal mass, which was biopsied. Pathology results were positive for invasive squamous cell carcinoma. He underwent an extensive neck surgery, including total thyroidectomy. Postsurgical laboratory results revealed serum corrected calcium of 7.6 mg/dL (ref 8.0-10.2 mg/dL) and parathyroid hormone <6.3 pg/mL (ref. 10-65). Despite treatment with calcium carbonate 12 g (elemental) daily, calcitriol and hydrochlorothiazide, his corrected serum calcium levels remained low. Patient also had a chyle leak that was treated with octreotide. Resolution of his hypocalcemia occurred after substitution of calcium carbonate with calcium citrate, cessation of octreotide, and management of the chyle leak.
DISCUSSION
Our patient likely developed recalcitrant hypocalcemia from: 1) postsurgical hypoparathyroidism, 2) a chyle leak, and 3) the use of octreotide. Administration of octreotide to seal the chyle leak most likely decreased gastric acid production and contributed to decrease in absorption of calcium carbonate. Oral calcium citrate may be better absorbed in this case.
CONCLUSION
Postsurgical hypoparathyroidism can lead to hypocalcemia. This case is unique in that the patient's chyle leak and the use of octreotide contributed to recalcitrant hypocalcemia.
PubMed: 38523859
DOI: 10.1016/j.aace.2024.01.003 -
Oncology Letters May 2024Glucagonomas are rare neuroendocrine neoplasms of the pancreas with malignant potential. At present, their epidemiology is not entirely clear, so clinicians are not well...
Glucagonomas are rare neuroendocrine neoplasms of the pancreas with malignant potential. At present, their epidemiology is not entirely clear, so clinicians are not well versed, lacking any consensus on diagnosis or comprehensive treatment. The present study reports the case of a 32-year-old woman hospitalized for recurrent glossitis, perioral dermatitis and necrolytic migratory erythema (NME) of both lower limbs. Imaging studies revealed a low-density nodule (~2 cm) in the tail of the pancreas, as well as multiple space-occupying hepatic lesions. Surgical intervention was then selected, and distal pancreatectomy, splenectomy and palliative metastasectomies were performed. Tissue examination subsequently confirmed a primary pancreatic neuroendocrine tumor (grade 2), metastatic to the liver. The NME resolved postoperatively, aided by intramuscular injections of long-acting release octreotide (30 mg) every 28 days. A series of three percutaneous ablative treatments (microwave ablation) were also undertaken within a 2-year period, targeting the liver metastases. The present condition of the patient is good, with no cutaneous relapse to date. Palliative metastasectomies, in conjunction with ablative treatments and combination somatostatin analog (SSA) use, are unique aspects of this case that, to the best of our knowledge, have yet to be documented in the literature. Surgical palliation may benefit patients with liver involvement and prolong their survival time. Likewise, ablative treatments and SSA injections delivered together not only address hepatic spread, but also control hormone-related symptoms, having a positive impact on prognosis. As glucagonomas are so rare, there is no real agreement on their management. The present study aims to guide clinical practice by adding further to the available data.
PubMed: 38516680
DOI: 10.3892/ol.2024.14336