In vitro and in vivo evaluation of bifunctional bisthiosemicarbazone 64Cu-complexes for the positron emission tomography imaging of hypoxia.

Journal of Medicinal Chemistry
Paul D BonnitchaJonathan R Dilworth

Abstract

The copper(II) bisthiosemicarbazonato complex, copper-diacetyl-bis(N4-methylthiosemicarbazonate) (Cu-ATSM), has been used clinically as a positron emission tomography (PET) tracer for the delineation of hypoxia. Six novel, asymmetric bis(thiosemicarbazones) derived from diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-amino-3-thiosemicarbazone) (H2ATSM/A), one of which contained a nitroimidazole functionality, were radiolabeled with 64Cu (t1/2=12.7 h, beta+=19.3%). In vitro studies were performed on three of the compounds using EMT6 mammary carcinoma cells under hypoxic and normoxic conditions. All compounds displayed rapid cellular association and appreciable hypoxic selectivity with increased uptake under normoxic and hypoxic conditions when compared to 64Cu-ATSM. Biodistribution and small animal PET imaging studies were then carried out in vivo using two compounds in EMT6 tumor-bearing mice. The compounds showed high tumor uptake, but also substantial accumulation in the liver. These complexes demonstrate that H 2ATSM/A represents a novel and versatile synthetic platform that can be utilized to provide hypoxic cell selectivity through functionalization of the bisthiosemicarbazonate group.

References

May 1, 1984·International Journal of Radiation Oncology, Biology, Physics·J E Moulder, S Rockwell
Jan 1, 1994·Advances in Experimental Medicine and Biology·M HöckelP Vaupel
Nov 1, 1996·Nuclear Medicine and Biology·P J BlowerJ Zweit
Jan 1, 1997·Nuclear Medicine and Biology·D W McCarthyM J Welch
Feb 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·J LewisM Welch
Feb 22, 2001·Journal of the National Cancer Institute·M Höckel, P Vaupel
Mar 22, 2002·Journal of Medicinal Chemistry·Richard I MaurerGregory E D Mullen
Apr 6, 2002·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jason L J DearlingPhilip J Blower
Jan 29, 2003·European Journal of Nuclear Medicine and Molecular Imaging·L S ZiemerC J Koch
Mar 26, 2003·International Journal of Radiation Oncology, Biology, Physics·Farrokh DehdashtiMichael J Welch
Apr 15, 2003·European Journal of Nuclear Medicine and Molecular Imaging·Farrokh DehdashtiBarry A Siegel
Dec 21, 2006·Dalton Transactions : an International Journal of Inorganic Chemistry·Andrew R CowleySteven J Ratcliffe
Nov 10, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·Amy L Vāvere, Jason S Lewis
Nov 10, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·Martin ChristliebJonathan R Dilworth
Jan 18, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Farrokh DehdashtiMichael J Welch

❮ Previous
Next ❯

Citations

Nov 17, 2009·European Journal of Nuclear Medicine and Molecular Imaging·Amanda J WeeksDaniel R Lloyd
Dec 23, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Christian R KowolBernhard K Keppler
Jun 13, 2009·Chemical Communications : Chem Comm·Lucy E Jennings, Nicholas J Long
Apr 22, 2010·Chemical Communications : Chem Comm·Laurence CarrollVéronique Gouverneur
Dec 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Paul S DonnellyPeter J Crouch
Sep 23, 2009·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·SinChun LimPaul S Donnelly
Nov 26, 2009·Journal of Inorganic Biochemistry·Paul D BonnitchaJonathan R Dilworth
Feb 26, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Jonathan R DilworthClaudiu T Supuran
May 3, 2019·Journal of Labelled Compounds & Radiopharmaceuticals·Taracad K VenkatachalamDavid C Reutens
Sep 27, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Douglas S MacPhersonBrian M Zeglis
May 7, 2016·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Fernando Cortezon-TamaritSofia I Pascu
Apr 2, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Jon D SilversidesStephen J Archibald
Jul 2, 2020·Organic & Biomolecular Chemistry·Jie GaoXianfeng Gu
Aug 3, 2020·Bioorganic & Medicinal Chemistry Letters·Renyu YangTaiwei Chu
Jan 23, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Viviana S PradoVictor M Deflon
Oct 18, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Simon R BaylyMartin Christlieb
Dec 18, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Rebekka HuetingRuth J Muschel
Jan 17, 2013·Journal of Medicinal Chemistry·Duraippandi PalanimuthuAshoka G Samuelson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

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.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

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.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.