Journal ArticleDOI
Synthesis and Evaluation of a Macrocyclic Actinium-225 Chelator, Quality Control and In Vivo Evaluation of 225 Ac-crown-αMSH Peptide.
Hua Yang,Chengcheng Zhang,Zheliang Yuan,Zheliang Yuan,Cristina Rodríguez-Rodríguez,Andrew Robertson,Valery Radchenko,Valery Radchenko,Randy Perron,Denise Gendron,Patrick Causey,Feng Gao,Francois Benard,Francois Benard,Paul Schaffer,Paul Schaffer,Paul Schaffer +16 more
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TLDR
A new Ac macrocyclic chelator named 'crown' is reported, which binds quantitatively and rapidly (< 15 min) to Ac at ambient temperature, which demonstrates dramatically different biodistrubution patterns of 225 Ac-crown-αMSH when subjected to different latency times before injection.Abstract:
Targeted alpha-therapy (TAT) has great potential for treating a broad range of late-stage cancers by delivering a focused and lethal radiation dose to tumors Actinium-225 (225 Ac) is an emerging alpha emitter suitable for TAT; however, the availability of chelators for Ac remains limited to a small number of examples (DOTA and macropa) Herein, we report a new Ac macrocyclic chelator named 'crown', which binds quantitatively and rapidly (<10 min) to Ac at ambient temperature We synthesized 225 Ac-crown-αMSH, a peptide targeting the melanocortin 1 receptor (MC1R), specifically expressed in primary and metastatic melanoma Biodistribution of 225 Ac-crown-αMSH showed favorable tumor-to-background ratios at 2 h post injection in a preclinical model In addition, we demonstrated dramatically different biodistrubution patterns of 225 Ac-crown-αMSH when subjected to different latency times before injection A combined quality control methodology involving HPLC, gamma spectroscopy and radioTLC is recommendedread more
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Journal ArticleDOI
Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications.
TL;DR: In this article, the authors discuss 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.
Journal ArticleDOI
Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The "Hopeful Eight".
TL;DR: In this article, the main properties of these eight chosen radionuclides are summarized and an overview from their availability to the resulting clinical studies, by way of chemical design and preclinical studies is discussed.
Journal ArticleDOI
The coordination properties and ionic radius of actinium: A 120-year-old enigma
TL;DR: In this article, the authors review progress made on the chemistry of lanthanides and actinides and reevaluate the structural data published on Ac3+ since the era of the Manhattan Project.
Journal ArticleDOI
Perspectives on metals-based radioimmunotherapy (RIT): moving forward.
TL;DR: In this article, the authors discuss approaches to develop radiometal-based radioimmunotherapy (RIT), including the selection of radiometals, chelators and antibody platforms (i.e. full-length, F(ab')2, Fab, minibodies, diabodies, scFv-Fc and nanobodies).
Journal ArticleDOI
Towards Targeted Alpha Therapy with Actinium-225: Chelators for Mild Condition Radiolabeling and Targeting PSMA—A Proof of Concept Study
Falco Reissig,David Bauer,David Bauer,Kristof Zarschler,Zbynek Novy,Katerina Bendova,Marie-Charlotte Ludik,Klaus Kopka,Klaus Kopka,Hans-Jürgen Pietzsch,Hans-Jürgen Pietzsch,Milos Petrik,Constantin Mamat,Constantin Mamat +13 more
TL;DR: In this article, two universal 225Ac-chelators were synthesized for mild condition radiolabeling and binding to conjugate molecules of pharmacological interest via the copper-mediated click chemistry.
References
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Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer
Chris Parker,Sten Nilsson,Sten Nilsson,D. Heinrich,Svein Inge Helle,Joe M. O'Sullivan,Sophie D. Fosså,Ales Chodacki,Paweł Wiechno,John P Logue,Mihalj Seke,Anders Widmark,D. C. Johannessen,Peter Hoskin,David Bottomley,Nicholas D. James,Arne Solberg,Isabel Syndikus,Ján Kliment,S. Wedel,S. Boehmer,Marcos F. Dall'Oglio,Lars Franzén,Robert E. Coleman,Nicholas J. Vogelzang,C.G. O'Bryan-Tear,K. Staudacher,J. Garcia-Vargas,M. Shan,Øyvind S. Bruland,Oliver Sartor +30 more
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Immune Checkpoint Blockade in Cancer Therapy
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Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors
Jonathan R. Strosberg,Ghassan El-Haddad,Edward M. Wolin,Andrew Eugene Hendifar,James C. Yao,Beth Chasen,Erik Mittra,Pamela L. Kunz,Matthew H. Kulke,Heather A. Jacene,David L. Bushnell,Thomas M. O'Dorisio,Richard A. Baum,Harshad R. Kulkarni,Martyn Caplin,Rachida Lebtahi,Timothy J. Hobday,Ebrahim S. Delpassand,E. Van Cutsem,Al B. Benson,Raj Srirajaskanthan,Marianne Pavel,J. Mora,Jordan Berlin,Enrique Grande,N. Reed,Ettore Seregni,Kjell Öberg,M. Lopera Sierra,P. Santoro,Thomas Thevenet,Jack L. Erion,Philippe Ruszniewski,Dirk Jan Kwekkeboom,E.P. Krenning +34 more
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Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma
Robert H.I. Andtbacka,Howard L. Kaufman,Frances A. Collichio,Thomas Amatruda,Neil Senzer,Jason Chesney,Keith A. Delman,Lynn E. Spitler,Igor Puzanov,Sanjiv S. Agarwala,Mohammed M. Milhem,Lee D. Cranmer,Brendan D. Curti,Karl D. Lewis,Merrick I. Ross,Troy H. Guthrie,Gerald P. Linette,Gregory A. Daniels,Kevin J. Harrington,Mark R. Middleton,Wilson H. Miller,Jonathan S. Zager,Yining Ye,Bin Yao,Ai Li,Susan Doleman,Ari M. Vanderwalde,Jennifer Gansert,Robert Coffin +28 more
TL;DR: T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial and represents a novel potential therapy for patients with metastatic melanoma.
Journal ArticleDOI
225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer.
Clemens Kratochwil,Frank Bruchertseifer,Frederik L. Giesel,Mirjam Weis,Frederik A. Verburg,Felix M. Mottaghy,Klaus Kopka,Christos Apostolidis,Uwe Haberkorn,Alfred Morgenstern +9 more
TL;DR: Targeted α-therapy with 225Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients.
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