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radionuclide therapy

Wen-Ting K Tsai, Anna M Wu
The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and fragments have been successfully used for molecular imaging and radioimmunotherapy (RIT) of cell-surface targets in oncology and immunology. Protein engineering has been employed for antibody humanization essential for clinical applications, as well as optimization of important characteristics including pharmacokinetics, biodistribution, and clearance...
March 14, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
Yusuf Menda, Mark T Madsen, Thomas M O'Dorisio, John Sunderland, Leonard G Watkins, Joseph S Dillon, Sarah L Mott, Michael King Schultz, Gideon K D Zamba, David L Bushnell, M Sue O'Dorisio
Pre-therapy PET imaging with86 Y-DOTATOC PET is considered the ideal dosimetry protocol for90 Y-DOTATOC therapy; however, its cost, low availability and the need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. Objectives: To develop a dosimetric method for90 Y-DOTATOC therapy using90 Y-DOTATOC PET/CT and Bremsstrahlung SPECT/CT imaging and to determine if dosimetry-based administered activities differed significantly from standard administered dosages. Materials and Methods: This is a prospective Phase 2 trial of90 Y-DOTATOC therapy in patients with somatostatin receptor positive tumors...
March 9, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Emily Vaughan, Joseph Machta, Martin Walker, Christos Toumpanakis, Martyn Caplin, Shaunak Navalkissoor
OBJECTIVE: To evaluate the efficacy and toxicity of a repeat peptide receptor radionuclide therapy (PRRT) course in neuroendocrine tumour (NET) patients who have progressed following previous PRRT and to identify factors contributing to retreatment outcomes. METHODS: This was a retrospective analysis of 47 consecutive patients who had been treated with PRRT (PRRT1) and following disease progression were retreated with a second course of PRRT (PRRT2). We reviewed patient, tumour and treatment characteristics, time to progression after PRRT1 and PRRT2, overall survival and toxicity...
March 7, 2018: British Journal of Radiology
Ján Kozempel, Olga Mokhodoeva, Martin Vlk
This review summarizes recent progress and developments as well as the most important pitfalls in targeted alpha-particle therapy, covering single alpha-particle emitters as well as in vivo alpha-particle generators. It discusses the production of radionuclides like211 At,223 Ra,225 Ac/213 Bi, labelling and delivery employing various targeting vectors (small molecules, chelators for alpha-emitting nuclides and their biomolecular targets as well as nanocarriers), general radiopharmaceutical issues, preclinical studies, and clinical trials including the possibilities of therapy prognosis and follow-up imaging...
March 5, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Marek Pruszynski, Matthias D'Huyvetter, Frank Bruchertseifer, Alfred Morgenstern, Tony Lahoutte
Human epidermal growth factor receptor type 2 (HER2) is overexpressed in numerous carcinomas. Nanobodies (Nbs) are the smallest antibody-derived fragments with beneficial characteristics for molecular imaging and radionuclide therapy. Therefore, HER2-targeting nanobodies could offer a valuable platform for radioimmunotherapy, especially when labeled with α-particle emitters, which provide highly lethal and localized radiation to targeted cells with minimal exposure to surrounding healthy tissues. In this study, the anti-HER2 2Rs15d-nanobody was conjugated with 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid ( p-SCN-Bn-DOTA) and radiolabeled with an α-emitter225 Ac with a high yield (>90%) and a radiochemical purity above 95%...
March 5, 2018: Molecular Pharmaceutics
Johan Spetz, Nils Rudqvist, Britta Langen, Toshima Z Parris, Johanna Dalmo, Emil Schüler, Bo Wängberg, Ola Nilsson, Khalil Helou, Eva Forssell-Aronsson
INTRODUCTION: Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with177 Lu-octreotate. Despite being highly effective in animal models,177 Lu-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for177 Lu-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. METHODS: GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq177 Lu-octreotate (non-curative amount) or mock-treated with saline solution...
February 6, 2018: Nuclear Medicine and Biology
Ulrike Garske-Román, Mattias Sandström, Katarzyna Fröss Baron, Lars Lundin, Per Hellman, Staffan Welin, Silvia Johansson, Tanweera Khan, Hans Lundqvist, Barbro Eriksson, Anders Sundin, Dan Granberg
PURPOSE: Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome. METHODS: The study group comprised 200 consecutive patients with metastasized somatostatin receptor-positive neuroendocrine tumours progressing on standard therapy or not suitable for other therapeutic options...
March 1, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Anders R Holmberg, Marcela Marquez, Lena Lennartsson, Lennart Meurling, Sten Nilsson
BACKGROUND/AIM: Prostate-specific membrane antigen (PSMA) is emerging as a target for treatment of castration-resistant prostate cancer (CRPC) while its up-regulated in the majority of CRPC tumors. The most common approach is targeted radionuclide therapy. MATERIALS AND METHODS: The PSMA binding pharmacophore Glu-Urea-Lysine (GUL) and lysine were conjugated to oxidized dextran with reductive amination and subsequently labelled with fluorosceinisothiocyanate (FITC)...
March 2018: Anticancer Research
Vojtěch Kubíček, Zuzana Böhmová, Romana Ševčíková, Jakub Vaněk, Přemysl Lubal, Zuzana Poláková, Romana Michalicová, Jan Kotek, Petr Hermann
H3 nota derivatives are among the most studied macrocyclic ligands and are widely used for metal ion binding in biology and medicine. Despite more than 40 years of chemical research on H3 nota, the comprehensive study of its solution chemistry has been overlooked. Thus, the coordination behavior of H3 nota with several divalent metal ions was studied in detail with respect to its application as a chelator for copper radioisotopes in medical imaging and therapy. In the solid-state structure of the free ligand in zwitterionic form, one proton is bound in the macrocyclic cavity through a strong intramolecular hydrogen-bond system supporting the high basicity of the ring amine groups (log Ka = 13...
February 28, 2018: Inorganic Chemistry
Christian H Pfob, Matthias Eiber, Peter Luppa, Florian Maurer, Tobias Maurer, Robert Tauber, Calogero D'Alessandria, Benedikt Feuerecker, Klemens Scheidhauer, Armin Ott, Uwe Heemann, Markus Schwaiger, Christoph Schmaderer
BACKGROUND: Amino acid co-infusion for renal protection in endoradiotherapy (ERT) applied as prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) or peptide receptor radionuclide therapy (PRRT) has been shown to cause severe hyperkalemia. The pathophysiology behind the rapid development of hyperkalemia is not well understood. We hypothesized that the hyperkalemia should be associated with metabolic acidosis. RESULTS: Twenty-two patients underwent ERT...
February 27, 2018: EJNMMI Research
Elisabeth Eppard, Ana de la Fuente, Nicole Mohr, Mareli Allmeroth, Rudolf Zentel, Matthias Miederer, Stefanie Pektor, Frank Rösch
BACKGROUND: In this work, the in vitro and in vivo stabilities and the pharmacology of HPMA-made homopolymers were studied by means of radiometal-labeled derivatives. Aiming to identify the fewer amount and the optimal DOTA-linker structure that provides quantitative labeling yields, diverse DOTA-linker systems were conjugated in different amounts to HPMA homopolymers to coordinate trivalent radiometals Me(III)* = gallium-68, scandium-44, and lutetium-177. RESULTS: Short linkers and as low as 1...
February 27, 2018: EJNMMI Research
Lisa Bodei, Mark S Kidd, Aviral Singh, Wouter A van der Zwan, Stefano Severi, Ignat A Drozdov, Jaroslaw Cwikla, Richard P Baum, Dik J Kwekkeboom, Giovanni Paganelli, Eric P Krenning, Irvin M Modlin
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) utilizes somatostatin receptor (SSR) overexpression on neuroendocrine tumors (NET) to deliver targeted radiotherapy. Intensity of uptake at imaging is considered related to efficacy but has low sensitivity. A pretreatment strategy to determine individual PRRT response remains a key unmet need. NET transcript expression in blood integrated with tumor grade provides a PRRT predictive quotient (PPQ) which stratifies PRRT "responders" from "non-responders"...
February 26, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Tomoyuki Ohya, Kotaro Nagatsu, Hisashi Suzuki, Masami Fukada, Katsuyuki Minegishi, Masayuki Hanyu, Ming-Rong Zhang
INTRODUCTION: Copper-67 is an attractive beta emitter for targeted radionuclide therapy. However, the availability of67 Cu limits its potential use in a wide range of applications. In this study, we propose an easy small-scale production of67 Cu using64 Ni target for a preclinical study. METHODS: 67 Cu was produced from an electrodeposited64 Ni target via the64 Ni(α, p)67 Cu-reaction with a 36 MeV alpha beam at 15 eμA (electrical microampere) conducted for 7 h...
February 20, 2018: Nuclear Medicine and Biology
Elisa Grassi, Federica Fioroni, Salvatore Berenato, Nick Patterson, Valentina Ferri, Luca Braglia, Angelina Filice, Annibale Versari, Mauro Iori, Emiliano Spezi
Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with177 Lu or90 Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation. A cohort of patients was extracted from the database of a clinical trial in PRRT...
January 2018: Physica Medica: PM
Caroline Stokke, Johan Blakkisrud, Ayca Løndalen, Jostein Dahle, Anne C T Martinsen, Harald Holte, Arne Kolstad
PURPOSE: 177 Lu-lilotomab satetraxetan is a novel anti-CD37 antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma (NHL). Four arms with different combinations of pre-dosing and pre-treatment have been investigated in a first-in-human phase 1/2a study for relapsed CD37+ indolent NHL. The aim of this work was to determine the tumor and normal tissue absorbed doses for all four arms, and investigate possible variations in the ratios of tumor to organs-at-risk absorbed doses...
February 22, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Duygu Has Şimşek, Yasemin Şanlı, Serkan Kuyumcu, Bora Başaran, Ayşe Mudun
OBJECTIVE: The aim of this study was to present our experience in the baseline evaluation of carotid body paragangliomas (CBP) with68 Ga-DOTATATE PET-CT. METHODS: Five patients (4F, 1M; age 24-73 years) with CBPs who underwent68 Ga-DOTATATE PET-CT scan before the treatment were evaluated retrospectively. PET-CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUVmax ). RESULTS: All patients had unilateral CBP lesion, showed intense68 Ga-DOTATATE uptake in PET-CT...
February 21, 2018: Annals of Nuclear Medicine
Rui Guo, Yun Xi, Min Zhang, Ying Miao, Miao Zhang, Biao Li
Novel treatment options are urgently required for patients with glioma who are not effectively treated through standard therapy. Human sodium iodide symporter (hNIS) is a molecular target of certain tumors types. Compared with131 I,188 Re possesses a higher energy and shorter half-life; therefore, the effects of188 Re and131 I were compared in hNIS-mediated gene imaging and therapy in the present study. Recombinant human brain glioma cell line U87 was transfected with a recombinant lentiviral vector containing hNIS (U87-hNIS)...
March 2018: Oncology Letters
Hanwen Zhang, Ananda Kumar Kanduluru, Pooja Desai, Afruja Ahad, Sean D Carlin, Nidhi Tandon, Wolfgang Weber, Philip S Low
Neurokinin 1 receptor (NK1R) is expressed in gliomas and neuroendocrine malignancies, and represents a promising target for molecular imaging and targeted radionuclide therapy. The goal of this study was to synthesize and evaluate a novel NK1R ligand (NK1R-NOTA) for targeting NK1R-expressing tumors. Using carboxymethyl moiety linked to L-733060 as starting reagent, NK1R-NOTA was synthesized in a 3-step reaction, and then labeled with64 Cu (or67 Ga for in vitro studies) in the presence of CH3 COONH4 buffer. The radioligand affinity and cellular uptake was evaluated with NK1R-transduced HEK293 cells (HEK293-NK1R) and NK1R non-transduced HEK293 cells (HEK293-WT) and its xenografts...
February 21, 2018: Bioconjugate Chemistry
Xi-Feng Jin, Matilde P Spampatti, Christine Spitzweg, Christoph J Auernhammer
Neuroendocrine tumors (NETs) are a group of rare and heterogeneous malignancies that can develop in various organs. A significant number of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is functionally active and presents with symptoms related to the secretion of biologically active substances, leading to the development of distinct clinical syndromes. There are various therapeutic approaches for GEP-NETs, including curative surgery, palliative surgery, local-ablative and loco-regional therapies as well as systemic therapeutic options including peptide receptor radionuclide therapy, cytotoxic therapy, and molecularly targeted therapies...
February 20, 2018: Reviews in Endocrine & Metabolic Disorders
L Jönsson, A Stenvall, E Mattsson, E Larsson, A Sundlöv, T Ohlsson, C Hindorf
BACKGROUND: Nuclear medicine imaging of neuroendocrine tumours is performed either by SPECT/CT imaging, using111 In-octreotide or by PET/CT imaging using68 Ga-radiolabelled somatostatin analogs. These imaging techniques will give different image quality and different detection thresholds for tumours, depending on size and activity uptake. The aim was to evaluate the image quality for111 In-SPECT and68 Ga-PET imaging, i.e. the smallest volume possible to visualize for different source-to-background activity ratios...
February 20, 2018: EJNMMI Physics
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