IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms15761.html
   My bibliography  Save this article

Synthesis and preliminary PET imaging of 11C and 18F isotopologues of the ROS1/ALK inhibitor lorlatinib

Author

Listed:
  • Thomas Lee Collier

    (Massachusetts General Hospital and Harvard Medical School
    Advion Inc.)

  • Marc D. Normandin

    (Massachusetts General Hospital and Harvard Medical School)

  • Nickeisha A. Stephenson

    (Massachusetts General Hospital and Harvard Medical School
    Present address: Department of Chemistry, University of the West Indies, Mona, Kingston 7, Jamaica)

  • Eli Livni

    (Massachusetts General Hospital and Harvard Medical School)

  • Steven H. Liang

    (Massachusetts General Hospital and Harvard Medical School)

  • Dustin W. Wooten

    (Massachusetts General Hospital and Harvard Medical School)

  • Shadi A. Esfahani

    (Massachusetts General Hospital and Harvard Medical School)

  • Michael G. Stabin

    (Vanderbilt University)

  • Umar Mahmood

    (Massachusetts General Hospital and Harvard Medical School)

  • Jianqing Chen

    (Pfizer Inc., Quantitative Medicine, Worldwide Research and Development)

  • Wei Wang

    (Pfizer Worldwide Research and Development)

  • Kevin Maresca

    (Pfizer Inc., Quantitative Medicine, Worldwide Research and Development)

  • Rikki N. Waterhouse

    (Pfizer Inc., Quantitative Medicine, Worldwide Research and Development
    Present address: Waterhouse Imaging and Biomarker Consultants, 208 Candia Road, Chester, New Hampshire 03036, USA)

  • Georges El Fakhri

    (Massachusetts General Hospital and Harvard Medical School)

  • Paul Richardson

    (Pfizer Worldwide Research and Development)

  • Neil Vasdev

    (Massachusetts General Hospital and Harvard Medical School)

Abstract

Lorlatinib (PF-06463922) is a next-generation small-molecule inhibitor of the orphan receptor tyrosine kinase c-ros oncogene 1 (ROS1), which has a kinase domain that is physiologically related to anaplastic lymphoma kinase (ALK), and is undergoing Phase I/II clinical trial investigations for non-small cell lung cancers. An early goal is to measure the concentrations of this drug in brain tumour lesions of lung cancer patients, as penetration of the blood–brain barrier is important for optimal therapeutic outcomes. Here we prepare both 11C- and 18F-isotopologues of lorlatinib to determine the biodistribution and whole-body dosimetry assessments by positron emission tomography (PET). Non-traditional radiolabelling strategies are employed to enable an automated multistep 11C-labelling process and an iodonium ylide-based radiofluorination. Carbon-11-labelled lorlatinib is routinely prepared with good radiochemical yields and shows reasonable tumour uptake in rodents. PET imaging in non-human primates confirms that this radiotracer has high brain permeability.

Suggested Citation

  • Thomas Lee Collier & Marc D. Normandin & Nickeisha A. Stephenson & Eli Livni & Steven H. Liang & Dustin W. Wooten & Shadi A. Esfahani & Michael G. Stabin & Umar Mahmood & Jianqing Chen & Wei Wang & Ke, 2017. "Synthesis and preliminary PET imaging of 11C and 18F isotopologues of the ROS1/ALK inhibitor lorlatinib," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15761
    DOI: 10.1038/ncomms15761
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms15761
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/ncomms15761?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jian Rong & Ahmed Haider & Troels E. Jeppesen & Lee Josephson & Steven H. Liang, 2023. "Radiochemistry for positron emission tomography," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15761. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.