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First-in-human experience of radiopharmaceutical therapy with [177Lu]Lu-DOTATATE in patients with advanced multiple myeloma.

Radiotheranostics using somatostatin receptor (R)-targeted agents has transformed the management of neuroendocrine tumors, yet its application in other oncological entities remains unexplored. Here, we report the firsSt-inST-human use of [177Lu]Lu-DOTATATE in two patients with advanced, triple-class refractory multiple myeloma, selected based on dual imaging with [68Ga]Ga-DOTATATE and [18F]F-FDG PET/CT. Both patients received standard activities of [177Lu]Lu-DOTATATE, resulting in favourable safety profiles and improved quality of life. One patient achieved sustained metabolic response and cli

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… Singh S Halperin D Myrehaug S Herrmann K Pavel M Kunz PL [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high–dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2–3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised … , phase 3 study Lancet Lond Engl 29 Juin 2024 403 10446 2807 2817 10.1016/S0140-6736(24)00701-3 38851203 Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz PL et al (2024) [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high–dose long-acting octreotide for the treatment of newly diagnosed …

Profile and Management of Toxicity of Selinexor and Belantamab Mafodotin for the Treatment of Triple Class Refractory Multiple Myeloma.

Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinical

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… One unrelated meta-analysis of eight randomized controlled trials found octreotide to be effective for severe cases of chemotherapy-induced diarrhea when compared to placebo (69% vs 54%). 27 , 28 Dysgeusia reported in 10–17% of the patients in Sel studies is common with many other therapies but lacks … Role of octreotide in post chemotherapy and/or radiotherapy diarrhea: prophylaxis or therapy? Asia Pac J Clin Oncol . 2014 ; 10 ( 2 ): e108 – e113 . doi: 10.1111/ajco.12055 23297685 29. Hovan AJ , Williams PM , Stevenson-Moore P , et al. …

Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications.

This review outlines the accomplishments and potential developments of targeted alpha (α) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of α-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common α-emitters, including 225Ac, 213Bi, 224Ra, 212Pb, 227Th, 223Ra, 211At, and 149Tb; the production techniques and proper handling of α-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinica

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… Clinical studies with Auger electrons for cancer therapy have been limited; however, some encouraging results were obtained using [ 111 In]In-DTPA-octreotide in rats with pancreatic tumors, [ 125 I]I-IUdR where tumor remissions were achieved, and [ 125 I]I-mAb 425 where the survival of glioblastoma patients … Evaluation of astatine-211-labeled octreotide as a potential radiotherapeutic agent for NSCLC treatment Bioorganic Med. Chem. 2018 26 1086 1091 10.1016/j.bmc.2018.01.023 29422331 92. Li H.K. Sugyo A. Tsuji A.B. Morokoshi Y. Minegishi K. Nagatsu K. Kanda H. Harada Y. Nagayama S. …

Learn from antibody-drug conjugates: consideration in the future construction of peptide-drug conjugates for cancer therapy.

Cancer is one of the leading causes of death worldwide due to high heterogeneity. Although chemotherapy remains the mainstay of cancer therapy, non-selective toxicity and drug resistance of mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed to improve clinical efficacy, also known as cocktail therapy. However, conventional "cocktail administration" is just passable, due to the potential toxicities to normal tissues and unsatisfactory synergistic effects, especially for the combined drugs with different pharmacokinetic properties. The drug

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… Replacing phenylalanine with tyrosine as the third amino acid in the octapeptide results in increased affinity to SSTR2, leading to the development of next-generation therapies of 90 Y-DOTA, Try 3 -octreotide. … The only difference between DOTA, Tyr 3 -octreotate and DOTA, Tyr 3 -octreotide is that the C-terminal threoninol of DOTA, Tyr 3 -octreotide is replaced with the threonine, improving binding to SSTR-positive tissues when compared with DOTA, Tyr 3 -octreotide [ 86 ]. …

A brief overview of targeted radionuclide therapy trials in 2022.

There is a growing use of radionuclide therapy for the medical care of oncology patients, where radioactive pharmaceuticals are used to target and treat various cancer types. This paper provides a brief overview illustrating the spectrum of ongoing and recently completed radionuclide therapy clinical trials in oncology. The trials selected highlight the potential of radionuclide therapies to provide a promising treatment option across a spectrum of cancer patients, while also discussing the importance of patient selection and monitoring, as well as potential side effects and safety concerns. U

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… NCT03273712 is a trial designed to evaluate the safety and efficacy of Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) with 90 Y-DOTA-tyr3-Octreotide ( 90 Y-DOTATOC) in patients with inoperable, somatostatin receptor-positive neuroendocrine tumors. … Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC). Clinicaltrials.gov ( 2017 ). Available at: https://clinicaltrials.gov/ct2/show/NCT03273712 (Accessed February 15, 2023) 9. …

Case Report with Literature Review: Tumor-induced osteomalacia from a soft-tissue phosphaturic mesenchymal tumor of the trunk.

BACKGROUND: Tumor-induced osteomalacia (TIO), a type of acquired hypophosphatemic osteomalacia, is brought on by tumors producing excessive levels of fibroblast growth factor 23, which raises renal phosphorus excretion. METHODS: Through a review of the literature, we have outlined the clinical characteristics of 33 patients with soft-tissue TIO of the trunk and described a case of TIO brought on by a soft-tissue tumor on the back. RESULTS: A 63-year-old woman who had been experiencing generalized bone pain for approximately three years visited the hospital. Physical examination revealed a ro

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… M, male; F, female; PMT, phosphaturic mesenchymal tumor; PMTMCT, phosphaturic mesenchymal tumor mixed connective tissue variant; NA, none; CT, computed tomography; MRI, magnetic resonance imaging; OCT, octreotide; PET/CT, positron emission tomography/computed tomography. … Conventional Octreoscan SPECT/CT imaging (e.g., 99mTc-octreotide SPECT/CT imaging or 111In-octreotide SPECT imaging) improves tumor detection ( 39 , 40 ), but its spatial resolution is limited. 68 Ga-DOTATATE, a 68 Ga-labeled somatostatin analog, binds to the PMT-expressed SSTR to localize tumors ( 41 …

Is There a Role for Bismuth in Diarrhea Management?

Diarrhea, an illness of both the developed and developing world, involves the burdensome characteristics of frequent bowel movements, loose stools, and abdominal discomfort. Diarrhea is a long-standing challenge in palliative care and can have a myriad of causes, making symptomatic treatment pertinent when illness evaluation is ongoing, when there is no definitive treatment approach, or when effective treatment cannot be attained. Symptomatic therapy is a common approach in palliative care settings. Bismuth is a suitable agent for symptomatic therapy and can be effectively employed for managem

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… Charcoal, 262 mg orally once daily, was initiated, in addition to octreotide 900 mg daily divided in three doses. Frequency and consistency of BM improved; soon after the octreotide was discontinued, while charcoal was titrated up to an oral amount of six doses daily. …

Pamidronate improves the quality of life and induces clinical remission of bone metastases in patients with thyroid cancer.

Skeletal metastases from thyroid cancer are poorly responsive to medical or radioiodine treatment. Bone destruction in skeletal metastases results from osteoclast-induced bone resorption. Therefore, a new approach in the therapy of bone metastases consists in using aminobisphosphonates, such as pamidronate, which are potent inhibitors of osteoclastic activity. In the present study, 10 thyroid cancer patients with painful osteolytic bone metastases were administered pamidronate (90 mg, as a 2 hour intravenous infusion) monthly for 12 consecutive cycles. Bone pain, quality of life, performance s

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… Treatment of advanced medullary thyroid carcinoma with a combination of recombinant interferon alpha-2b and octreotide. Cancer. 1996 Sep 1;78(5):1114–1118. doi: 10.1002/(SICI)1097-0142(19960901)78:5<1114::AID-CNCR23>3.0.CO;2-4. …

Tumor Targeting with Peptide-Drug Conjugates: Showcasing Key Progress and Hurdles.

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs' small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circul

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… radiolabel, was FDA-approved in 2018 for gastroenteropancreatic neuroendocrine tumors. 3 , 4 This agent utilizes peptide receptor radionuclide therapy (PRRT) to selectively target somatostatin receptor-positive tumors, resulting in a significant improvement in progression-free survival compared to high-dose octreotide … had significantly improved progression-free survival, overall response rates, and overall survival compared with those treated with octreotide alone. …

Clinical Experience with Targeted Alpha-Emitter Peptide Receptor Radionuclide Therapy (α-PRRT) for Somatostatin Receptor-Positive Neuroendocrine Tumors.

Background: α-emitting Peptide Receptor Radionuclide Therapy (α-PRRT) is emerging as a promising new generation of PRRT for neuroendocrine tumors (NETs), providing enhanced tumor cell cytotoxicity and reduced irradiation of adjacent healthy tissues due to its high linear energy transfer (LET) and short particle range. This review summarizes available clinical evidence on α-PRRT using different α-emitting isotopes, including actinium-225, lead-212, and bismuth-213, in somatostatin receptor (SSTR)-positive NETs. Methods: A comprehensive literature search was conducted across PubMed, Embase, Coch

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… Both the NETTER-1 and NETTER-2 clinical studies compared the use of [ 177 Lu]Lu-DOTATATE and long-acting octreotide as treatment of NETs against a control treatment of high-dose long-acting octreotide in locally advanced or metastatic midgut G1-G2 NETs and G2-G3 gastroenteropancreatic (GEP) NETs, respectively … Strosberg J.R., Caplin M.E., Kunz P.L., Ruszniewski P., Bodei L., Hendifar A., Mitrra E., Wolin E., Yao J., Pavel M., et al. 177Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): Final overall survival and long-term …

Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications.

Over the past two decades, peptide drug discovery has experienced a remarkable renaissance, with organic chemistry and biotechnology emerging as pivotal tools for developing peptidomimetics that exhibit improved stability, specificity, and bioavailability compared to conventional peptides. This review systematically examines methodologies for modifying peptide backbones to achieve targeted properties, highlighting recent advances facilitated by modern biotechnological innovations for novel molecular transformations. Additionally, the review emphasizes the practical applications of peptides and

A Phase II Trial of a Histone Deacetylase Inhibitor Panobinostat in Patients With Low-Grade Neuroendocrine Tumors.

Lessons learnedPancreatic neuroendocrine tumors versus carcinoid tumors should be examined separately in clinical trials.Progression-free survival is more clinically relevant as the primary endpoint (rather than response rate) in phase II trials for low-grade neuroendocrine tumors.BackgroundThe most common subtypes of neuroendocrine tumors (NETs) are pancreatic islet cell tumors and carcinoids, which represent only 2% of all gastrointestinal malignancies. Histone deacetylase (HDAC) inhibitors have already been shown to suppress tumor growth and induce apoptosis in various malignancies. In NET

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… First-line therapy involves a somatostatin analog, such as octreotide long-acting repeatable. … For patients with well-differentiated and functional tumors, somatostatin analogs such as octreotide long-acting repeatable are the mainstay of treatment for control tumor growth as well as symptomatic control, with improved PFS and quality of life [ 4 , 5 ]. …

Current and upcoming radionuclide therapies in the direction of precision oncology: A narrative review.

As new molecular tracers are identified to target specific receptors, tissue, and tumor types, opportunities arise for the development of both diagnostic tracers and their therapeutic counterparts, termed "theranostics." While diagnostic tracers utilize positron emitters or gamma-emitting radionuclides, their theranostic counterparts are typically bound to beta and alpha emitters, which can deliver specific and localized radiation to targets with minimal collateral damage to uninvolved surrounding structures. This is an exciting time in molecular imaging and therapy and a step towards personal

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… In the NETTER-1 study which led to FDA approval of Lu-177-DOTATATE for midgut NET [39] , 229 patients were randomly assigned to either PRRT or long-acting repeatable Octreotide. … Pre-clinical comparison of [DTPA0] octreotide, [DTPA0,Tyr3] octreotide and [DOTA0,Tyr3] octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy Int. J. …

Panniculitis and pancreatitis: Inflammation and necrotic mechanisms in a patient with alcohol use disorder and alarming suspicion for malignant process.

Panniculitis is an inflammatory process localized to subcutaneous tissue, with etiologies including infection, malignancy, external insults, enzymatic destructive processes, and inflammatory disorders. The incidence of panniculitis manifesting as necrosis of subcutaneous fat tissue associated with pancreatic diseases is low, which may encompass associated periarthritis with bone necrosis and panniculitis (Pancreatitis, panniculitis and polyarthritis syndrome). Pancreatitis, panniculitis and polyarthritis syndrome is considered to derive from the systemic activity of enzymes within the pancreas

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… Octreotide, which is thought to reduce pancreatic secretion, and plasmapheresis have been used in adjunctive therapy in previous cases [9] . …

A Look to the Future: Potential Theranostic Applications in Head and Neck Tumors.

Theranostics, the practice of using a diagnostic radiopharmaceutical to guide radiotherapy with a chemically identical (or nearly identical) therapeutic radiopharmaceutical, is an exciting new field under development within the auspices of nuclear medicine. We aim to provide a narrative review of the areas of theranostics use and development which are occurring specifically in the head and neck, with attention to the therapeutic use of existing diagnostically used radiotracers such as agents that target prostate-specific membrane antigen (PSMA) and somatostatin receptors (e.g., DOTATATE deriva

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… Strosberg J.R., Caplin M.E., Kunz P.L., Ruszniewski P.B., Bodei L., Hendifar A., Mittra E., Wolin E.M., Yao J.C., Pavel M.E., et al. (177)Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): Final overall survival and …

Metastasis в качестве первоначального представления Carcinoid Tumor: Case Report and Literical Review.

Нейроэндокринные новообразования легких включают нейроэндокринные карциномы и нейроэндокринные опухоли (НЕТ). НЕТ также известны как карциноидные опухоли (CaTs), которые классифицируются как типичные карциноиды и атипичные карциноиды (AC). Легкие котлы часто метастазируют в различные места, включая региональные лимфатические узлы, легкие, печень и кости; однако метастаз в мозге относительно редкий. Для пациентов с Кэтс еще реже показывать признаки метастаза головного мозга. Мы сообщаем о случае 50-летней пациентки, у которой первоначально появились неврологические симптомы и магнитно-резонансн

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… Chest and abdominal CT • FDG PET-CT • 68-Gallium-DOTATATE PET/CT scan • Chemotherapy • Total excision of brain tumor None Our case 2023 50/F Neck pain, dizziness, numbness, and paresthesia in upper limbs Lung • Brain MRI • FDG PET/CT • 68-Gallium-DOTATATE PET/CT scan • Radiotherapy • Chemotherapy • Octreotide … The predominant imaging technique for diagnosis, staging, and monitoring is frequently SSTR scintigraphy using 111 In-octreotide. …

Dethroning of Neuroendocrine Tumor as an Orphan Disease: US Incidence, Prevalence, and Survival in the 21st Century.

Importance: Neuroendocrine tumors (NETs) have traditionally been considered rare (orphan) diseases; however, improvements in diagnostic methods and heightened awareness about NETs may have altered their epidemiologic profile in the U.S. Objective: To evaluate trends in incidence, prevalence, and survival of NETs in the United States from 2000 to 2021 using updated data from the SEER-22 registry. Method: This population-based, retrospective cohort study used the SEER-22 database for incidence, prevalence, and survival analyses. Data included 231,659 patients diagnosed with NETs between 2000 and

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… The 2017 NETTER-1 trial confirmed that 177Lu-Dotatate provided superior PFS (median: not reached versus 8.4 months) and response rates compared to high-dose octreotide LAR in advanced midgut NET patients, with an 11.7-month difference in median OS reported in the final analysis in 2021 (median: 48.0 … Strosberg J.R., Caplin M.E., Kunz P.L., Ruszniewski P.B., Bodei L., Hendifar A., Mittra E., Wolin E.M., Yao J.C., Pavel M.E. 177Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): Final overall survival and long-term …

Acute Esophageal Necrosis: A Case Series From a Safety Net Hospital.

Acute esophageal necrosis (AEN) or "black esophagus" is a rare clinical condition, endoscopically characterized by diffuse circumferential black esophageal mucosa. Etiologies include hypoperfusion, infections, and corrosive injury. Consideration of this condition as a differential diagnosis is important, as early diagnosis and treatment has implications on survival. In this article, we present four unique cases of acute esophageal necrosis who were managed conservatively.

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… He was transferred to the medical intensive care unit for upper gastointestinal bleeding and initially managed with intravenous fluids, intravenous pantoprazole, and octreotide drip. …

Прогресс в развитии лекарственных средств на основе пептида: платформы для доставки, терапевтические средства и вакцины.

Успешное утверждение лекарств на основе пептида можно отнести на счет совместных усилий по целому ряду дисциплин. Интеграция новых методов разработки и синтеза лекарственных средств, отображение библиотечных технологий, систем доставки, достижений в области биоинженерии и искусственного интеллекта в значительной степени ускорила разработку новейших лекарств на основе пептида, эффективно устраняя препятствия, связанные с их характером, такие, как быстрое обезвреживание и деградация, необходимость субколичественной инъекции, ведущей к усилению дискомфорта пациентов, и в конечном итоге продвигая

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… 802 octreotide/RGD 18 F NOTA PET or GEP-NETs Neuroendocrine tumors NCT04552847 (2020)/ NCT03883776 (2020) Phase I/II/III 17 [18 F]Fluciclatide 800 RGD 18 F PEG PET imaging NCT00918281 (2014) Phase II 18 [18 F]RGD-K5 160 cyclo (RGDfK) 18 F NOTA PET imaging NCT03364270 (2020) Phase II 19 68Ga-NODAGA-E … 802 | octreotide/RGD | 18 F | NOTA | PET or GEP-NETs Neuroendocrine tumors | NCT04552847 (2020)/ NCT03883776 (2020) Phase I/II/III 17 | [18 F]Fluciclatide 800 | RGD | 18 F | PEG | PET imaging | NCT00918281 (2014) Phase II 18 | [18 F]RGD-K5 160 | cyclo (RGDfK) | 18 F | NOTA | PET imaging | NCT03364270 …

Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O6-methylguanine DNA methyltransferase as a biomarker for response.

Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O6-methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progressio

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… The only phase II data for CAPTEM was presented at the 2014 ASCO session, and included 28 patients with metastatic grade 1 and 2 NETs including typical and atypical carcinoid tumors, pituitary, pancreatic NET, and medullary thyroid cancers, who progressed on octreotide. … | 3% Carotid Body | 1 | 3% Unknown | 3 | 8% Prior Therapy | | Regional therapy | 21 | 55% Surgery | 14 | 37% TACE/RFA/SIRT | 12 | 32% No prior systemic therapy | 17 | 45% Prior Systemic therapy | 21 | 55% Temozolomide alone | 3 | 8% Platinum Chemotherapy | 10 | 26% mTOR inhibitor | 9 | 24% Prior Octreotide …