Measuring the pharmacodynamic effects of a novel Hsp90 inhibitor on HER2/neu expression in mice using Zr-DFO-trastuzumab.

PloS One
Jason P HollandJason S Lewis

Abstract

The positron-emitting radionuclide (89)Zr (t(1/2) = 3.17 days) was used to prepare (89)Zr-radiolabeled trastuzumab for use as a radiotracer for characterizing HER2/neu-positive breast tumors. In addition, pharmacodynamic studies on HER2/neu expression levels in response to therapeutic doses of PU-H71 (a specific inhibitor of heat-shock protein 90 [Hsp90]) were conducted. Trastuzumab was functionalized with desferrioxamine B (DFO) and radiolabeled with [(89)Zr]Zr-oxalate at room temperature using modified literature methods. ImmunoPET and biodistribution experiments in female, athymic nu/nu mice bearing sub-cutaneous BT-474 (HER2/neu positive) and/or MDA-MB-468 (HER2/neu negative) tumor xenografts were conducted. The change in (89)Zr-DFO-trastuzumab tissue uptake in response to high- and low-specific-activity formulations and co-administration of PU-H71 was evaluated by biodistribution studies, Western blot analysis and immunoPET. (89)Zr-DFO-trastuzumab radiolabeling proceeded in high radiochemical yield and specific-activity 104.3+/-2.1 MBq/mg (2.82+/-0.05 mCi/mg of mAb). In vitro assays demonstrated >99% radiochemical purity with an immunoreactive fraction of 0.87+/-0.07. In vivo biodistribution experiments revealed high speci...Continue Reading

References

Dec 1, 1992·International Journal of Radiation Applications and Instrumentation. Part A, Applied Radiation and Isotopes·W E MeijsH M Pinedo
May 1, 1990·Nuclear Medicine Communications·J C WatkinsonS E Clarke
May 1, 1996·Nuclear Medicine and Biology·W E MeijsJ D Herscheid
Apr 1, 1997·Cancer Immunology, Immunotherapy : CII·F B van GogG A van Dongen
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Jul 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John Mendelsohn, Jose Baselga
Sep 25, 2003·Cancer Biotherapy & Radiopharmaceuticals·Iris VerelGuus A M S van Dongen
May 11, 2004·Nature Biotechnology·Peter M Smith-JonesSteven M Larson
Jun 10, 2004·Cancer Biotherapy & Radiopharmaceuticals·Adrienne BrouwersOtto Boerman
Jul 23, 2004·Anti-cancer Drugs·Jason Beliakoff, Luke Whitesell
Aug 4, 2004·European Journal of Nuclear Medicine and Molecular Imaging·Iris VerelGuus A M S van Dongen
May 3, 2005·Nature Reviews. Cancer·Nancy E Hynes, Heidi A Lane
Sep 10, 2005·Nature Biotechnology·Anna M Wu, Peter D Senter
Apr 13, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pontus K E BörjessonGuus A M S van Dongen
May 20, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick J PerikElisabeth G E de Vries
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Ami Citri, Yosef Yarden
Jul 13, 2006·European Journal of Nuclear Medicine and Molecular Imaging·Lars R PerkGuus A M S van Dongen
Aug 8, 2006·Seminars in Oncology·John Mendelsohn, Jose Baselga
Aug 21, 2007·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jin Su KimDae Hyuk Moon
Aug 21, 2007·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Kristy E BaileyKatherine A Vallis
Oct 9, 2007·Nuclear Medicine and Biology·C Andrew Boswell, Martin W Brechbiel
Jan 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sarat ChandarlapatyDavid B Solit
Jan 15, 2008·Drug Discovery Today·David B Solit, Gabriela Chiosis
May 21, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Lars R PerkGuus A M S van Dongen
Jun 10, 2008·The Cancer Journal·Anna M Wu, Tove Olafsen
Jul 1, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Pat Zanzonico
Jul 23, 2008·Current Opinion in Pharmacology·Tony TaldoneGabriela Chiosis
Aug 16, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Danny L CostantiniRaymond M Reilly
Nov 20, 2008·Bioorganic & Medicinal Chemistry·Tony TaldoneGabriela Chiosis
Dec 19, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Anna M Wu
Dec 19, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Hugo J W L AertsPhilippe Lambin
Jan 8, 2009·Bioconjugate Chemistry·Tapan K Nayak, Martin W Brechbiel
Feb 12, 2009·Current Opinion in Cell Biology·Nancy E Hynes, Gwen MacDonald
Feb 19, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Anna OrlovaVladimir Tolmachev
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Eloisi Caldas-LopesGabriela Chiosis
May 15, 2009·European Journal of Nuclear Medicine and Molecular Imaging·Gang NiuXiaoyuan Chen
May 16, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Eli C F DijkersMarjolijn N Lub-de Hooge
Jun 16, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Gabriela Kramer-MarekJacek Capala
Jun 19, 2009·Nature Reviews. Cancer·José Baselga, Sandra M Swain
Jun 27, 2009·Accounts of Chemical Research·Megan E FoxJean M J Fréchet
Sep 2, 2009·Nuclear Medicine and Biology·Jason P HollandJason S Lewis
Oct 20, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Pontus K E BörjessonRonald Boellaard

❮ Previous
Next ❯

Citations

Dec 10, 2013·Inorganic Chemistry·Brian M ZeglisJason S Lewis
Nov 19, 2010·Radiology·Stephen B Solomon, Stuart G Silverman
Apr 30, 2011·Future Medicinal Chemistry·Oluwatayo F Ikotun, Suzanne E Lapi
Apr 12, 2014·Dalton Transactions : an International Journal of Inorganic Chemistry·Jason P Holland, Neil Vasdev
Jul 6, 2014·BioMed Research International·Floor C J van de WateringOtto C Boerman
Jan 25, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Guus A M S van DongenDanielle J Vugts
Jul 28, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jason P HollandJason S Lewis
Nov 3, 2010·International Journal of Nanomedicine·Alessandro RuggieroMichael R McDevitt
Mar 23, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Carola HeneweerJason S Lewis
Mar 29, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Brian M Zeglis, Jason S Lewis
May 5, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Sibaprasad Bhattacharyya, Manish Dixit
Sep 13, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Alessandro RuggieroJan Grimm
Sep 25, 2012·Nature Medicine·Jason P HollandJason S Lewis
Oct 9, 2013·Nuclear Medicine Communications·Volkan BeylergilTimothy J Akhurst
Mar 9, 2013·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Arutselvan NatarajanSanjiv Sam Gambhir
Jul 24, 2010·Nature Reviews. Cancer·Jane TrepelLen Neckers
Aug 17, 2010·Cancer Biotherapy & Radiopharmaceuticals·Guus A M S van Dongen, Maria J W D Vosjan
Jun 6, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gabriel FischerCarmen Wängler
Mar 29, 2014·Expert Opinion on Investigational Drugs·Komal JhaveriGabriela Chiosis
Mar 9, 2012·Expert Opinion on Drug Discovery·Hardik J PatelTony Taldone
Sep 25, 2012·Nuclear Medicine and Biology·Melissa A DeriJason S Lewis
Jul 1, 2011·Drug Discovery Today. Technologies·Danielle J Vugts, Guus A M S van Dongen
Jul 2, 2011·Nuclear Medicine and Biology·Diane S AbouPeter M Smith-Jones
Nov 26, 2015·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Mai LinCarlos González-Lepera
Sep 17, 2013·Medicinal Research Reviews·Emily B Corcoran, Robert N Hanson
Jun 1, 2011·Seminars in Nuclear Medicine·Samuel L RiceJason S Lewis
Nov 9, 2011·Biochimica Et Biophysica Acta·Komal JhaveriGabriela Chiosis
Apr 4, 2012·Molecular Oncology·Moritz F KircherSteven M Larson
Sep 19, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Scott M Knowles, Anna M Wu
Apr 5, 2017·Nuclear Medicine and Biology·Stacy Lee QueernSuzanne Elizabeth Lapi
Jun 27, 2017·Organic & Biomolecular Chemistry·Tomas Richardson-SanchezRachel Codd
Dec 13, 2017·Journal of Labelled Compounds & Radiopharmaceuticals·Eszter Boros, Jason P Holland
Jan 1, 2012·Pharmaceuticals·Albert J ChangSuzanne Lapi
Jan 6, 2015·Chemical Communications : Chem Comm·Darpan N PandyaThaddeus J Wadas
Jul 4, 2012·Therapeutic Advances in Medical Oncology·Robert B Den, Bo Lu
Jun 27, 2018·Rapid Communications in Mass Spectrometry : RCM·Thomas De VijlderDarrel J Pemberton
Jun 30, 2018·Chemistry : a European Journal·Jason P Holland
Jan 23, 2014·Molecular Imaging·Alexander ZheleznyakSuzanne E Lapi
Dec 6, 2018·Angewandte Chemie·Malay PatraJason P Holland
Feb 1, 2019·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Thomas J TelferRachel Codd
Oct 10, 2013·Dalton Transactions : an International Journal of Inorganic Chemistry·Eric W PriceChris Orvig

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
size-exclusion chromatography
Protein Assay

Software Mentioned

Adobe Photoshop
Win
Un
ASIPro VMâ¢
Scan
It
Scan Radio - TLC

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.