Design and synthesis of 225Ac radioimmunopharmaceuticals

Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine
Michael R McDevittDavid A Scheinberg


The alpha-particle-emitting radionuclides 213Bi, 211At, 224Ra are under investigation for the treatment of leukemias, gliomas, and ankylosing spondylitis, respectively. 213Bi and 211At were attached to monoclonal antibodies and used as targeted immunotherapeutic agents while unconjugated 224Ra chloride selectively seeks bone. 225Ac possesses favorable physical properties for radioimmunotherapy (10d half-life and 4 net alpha particles), but has a history of unfavorable radiolabeling chemistry and poor metal-chelate stability. We selected functionalized derivatives of DOTA as the most promising to pursue from out of a group of potential 225Ac chelate compounds. A two-step synthetic process employing either MeO-DOTA-NCS or 2B-DOTA-NCS as the chelating moiety was developed to attach 225Ac to monoclonal antibodies. This method was tested using several different IgG systems. The chelation reaction yield in the first step was 93+/-8% radiochemically pure (n=26). The second step yielded 225Ac-DOTA-IgG constructs that were 95+/-5% radiochemically pure (n=27) and the mean percent immunoreactivity ranged from 25% to 81%, depending on the antibody used. This process has yielded several potential novel targeted 225Ac-labeled immunotherapeut...Continue Reading


Apr 1, 1995·Nuclear Medicine and Biology·T K NikulaDavid A Scheinberg
Feb 1, 1993·Nuclear Medicine Communications·M W GeerlingsR van der Hout
Jan 1, 1996·Acta Oncologica·M R Zalutsky, D D Bigner
Sep 2, 1998·European Journal of Nuclear Medicine·Michael R McDevittDavid A Scheinberg
Apr 24, 1999·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Michael R McDevittDavid A Scheinberg
Jul 30, 1999·Journal of Medicinal Chemistry·K A DealM W Brechbiel
Sep 3, 1999·Nuclear Medicine and Biology·I A DavisS J Kennel
Jul 21, 2000·Current Pharmaceutical Design·M R Zalutsky, G Vaidyanathan
Nov 17, 2001·Science·Michael R McDevittDavid A Scheinberg


Jan 15, 2004·European Journal of Nuclear Medicine and Molecular Imaging·G-J BeyerF Buchegger
Oct 16, 2007·Bioconjugate Chemistry·Stavroula SofouGeorge Sgouros
Mar 29, 2006·Dalton Transactions : an International Journal of Inorganic Chemistry·Phil Blower
Jul 28, 2010·Assay and Drug Development Technologies·Jonathan H SeidemanDavid A Scheinberg
Jul 27, 2007·Cancer Biotherapy & Radiopharmaceuticals·R H LarsenØ S Bruland
Nov 13, 2008·Cancer Biotherapy & Radiopharmaceuticals·George Sgouros
Aug 25, 2007·The Journal of Clinical Investigation·Jaspreet Singh JaggiDavid A Scheinberg
Mar 19, 2013·PloS One·Yanyan GuoLee Josephson
Apr 8, 2009·Critical Reviews in Immunology·Hideho OkadaMitsugu Fujita
Nov 3, 2010·International Journal of Nanomedicine·Alessandro RuggieroMichael R McDevitt
Jul 24, 2014·AJR. American Journal of Roentgenology·Thaddeus J WadasAkiva Mintz
Jun 3, 2008·Advanced Drug Delivery Reviews·Matthias MiedererMichael R McDevitt
Apr 15, 2014·Nihon rinsho. Japanese journal of clinical medicine·Nozomi Niitsu
Dec 15, 2005·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Anthony S BonaviaDavid A Scheinberg
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Alireza Khorami-MoghadamBehrouz Alirezapour
Oct 11, 2015·Nuclear Medicine and Biology·Behrouz AlirezapourSedigheh Moradkhani
Jan 10, 2012·Cancer Treatment Reviews·Chen-Yu HuangBarry J Allen
Feb 17, 2015·Nuclear Medicine and Biology·Justin J WilsonEva R Birnbaum
May 30, 2014·Targeted Oncology·Evan D ReadTerrence J Piva
May 5, 2016·Expert Opinion on Biological Therapy·Yana DekempeneerNick Devoogdt
Mar 1, 2006·International Journal of Radiation Oncology, Biology, Physics·Jaspreet Singh JaggiDavid A Scheinberg
Apr 20, 2004·Nuclear Medicine and Biology·Gjermund HenriksenR H Larsen
Aug 18, 2017·Chemistry : a European Journal·Peter CombaMiriam Starke
Jan 19, 2018·Annual Review of Biomedical Engineering·Michael R McDevittStavroula Sofou
Jun 12, 2018·Cancer Biotherapy & Radiopharmaceuticals·Nikki A Thiele, Justin J Wilson
Oct 1, 2017·Angewandte Chemie·Nikki A ThieleJustin J Wilson
Jul 1, 2005·Journal of the American Society of Nephrology : JASN·Jaspreet Singh JaggiDavid A Scheinberg
Nov 1, 2013·Chemical Society Reviews·Eric W Price, Chris Orvig
Jul 21, 2005·Technology in Cancer Research & Treatment·Serengulam V GovindanDavid M Goldenberg
Apr 20, 2013·Chemical Communications : Chem Comm·Caterina F Ramogida, Chris Orvig
Apr 25, 2018·Nature Communications·Michael R McDevittDavid Ulmert
Nov 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Narges K TafreshiDavid L Morse
Dec 21, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·M Toro-GonzálezJ V Rojas
Jun 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mesude BicakDavid Ulmert
Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthias MiedererDavid A Scheinberg
Jul 9, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ase M BallangrudGeorge Sgouros
Nov 28, 2019·Cancer Research·Alireza KarimianGeorge Sgouros
Oct 26, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sophie PotyJason S Lewis
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthias MiedererMarkus Essler
Jun 3, 2005·Cancer Research·Jaspreet Singh JaggiDavid A Scheinberg
Dec 4, 2020·Journal of Labelled Compounds & Radiopharmaceuticals·Sareh Abbas AbadiSamaneh Zolghadri
Feb 10, 2021·Nuclear Medicine and Biology·Jasmine L Hatcher-LamarreLynn C Francesconi

Related Concepts

Monoclonal Antibodies

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Systemic Juvenile Idiopathic Arthritis

Systemic juvenile idiopathic arthritis is a rare rheumatic disease that affects children. Symptoms include joint pain, but also fevers and skin rashes. Here is the latest on this disease.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Pontocerebellar Hypoplasia

Pontocerebellar hypoplasias are a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. Here is the latest research on pontocerebellar hypoplasia.

Cell Atlas Along the Gut-Brain Axis

Profiling cells along the gut-brain axis at the single cell level will provide unique information for each cell type, a three-dimensional map of how cell types work together to form tissues, and insights into how changes in the map underlie health and disease of the GI system and its crosstalk with the brain. Disocver the latest research on single cell analysis of the gut-brain axis here.

Chronic Traumatic Encephalopathy

Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease that occurs in individuals that suffer repetitive brain trauma. Discover the latest research on traumatic encephalopathy here.