CEACAM5-targeted immuno-PET in androgen receptor-negative prostate cancer Journal Article


Authors: Imberti, C.; De Gregorio, R.; Korsen, J. A.; Hoang, T. T.; Khitrov, S.; Kalidindi, T.; Nandakumar, S.; Park, J.; Zaidi, S.; Pillarsetty, N. V. K.; Lewis, J. S.
Article Title: CEACAM5-targeted immuno-PET in androgen receptor-negative prostate cancer
Abstract: The incidence of androgen receptor (AR)-negative (AR-) prostate cancer, including aggressive neuroendocrine prostate cancer (NEPC), has more than doubled in the last decade, but its timely diagnosis is difficult as it lacks typical prostate cancer hallmarks. The carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) has recently been identified as an upregulated surface antigen in NEPC. We developed an immuno-PET agent targeting CEACAM5 and evaluated its ability to delineate AR- prostate cancer in vivo. Methods: CEACAM5 expression was evaluated in a panel of prostate cancer cell lines by immunohistochemistry and Western blotting. The CEACAM5-targeting antibody labetuzumab was conjugated with the chelator desferrioxamine (DFO) and radiolabeled with 89Zr. The in vivo distribution of the radiolabeled antibody was evaluated in xenograft prostate cancer models by PET imaging and ex vivo organ distribution. Results: The NEPC cell line H660 exhibited strong CEACAM5 expression, whereas expression was limited in the AR- cell lines PC3 and DU145 and absent in the AR-positive cell line LNCaP. [89Zr]Zr-DFO-labetuzumab imaging was able to clearly delineate both neuroendocrine H660 xenografts and AR- DU145 in vivo but could not detect the AR-positive xenograft LNCaP. Conclusion: Immuno-PET imaging with [89Zr]Zr-DFO-labetuzumab is a promising diagnostic tool for AR- prostate cancer. © 2024 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords: positron emission tomography; mouse; animal; metabolism; animals; mice; carcinoembryonic antigen; pathology; molecular imaging; cell line, tumor; diagnostic imaging; prostatic neoplasms; tissue distribution; prostate tumor; tumor cell line; positron-emission tomography; cell adhesion molecules; androgen receptor; antigens, cd; radioisotope; receptors, androgen; radioisotopes; leukocyte antigen; zirconium; zirconium-89; cell adhesion molecule; immuno-pet; gpi-linked proteins; glycosylphosphatidylinositol anchored protein; humans; human; male; androgen receptor–negative prostate cancer; ceacam5; ceacam5 protein, human
Journal Title: Journal of Nuclear Medicine
Volume: 65
Issue: 7
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2024-07-01
Start Page: 1043
End Page: 1050
Language: English
DOI: 10.2967/jnumed.123.267107
PUBMED: 38782457
PROVIDER: scopus
PMCID: PMC11218725
DOI/URL:
Notes: Article -- MSK corresponding authors are Naga Vara Kishore Pillarsetty and Jason Lewis -- Source: Scopus
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MSK Authors
  1. Jason S Lewis
    456 Lewis
  2. Joshua Aaron Korsen
    12 Korsen
  3. Samir Zaidi
    27 Zaidi
  4. Tran Tu Hoang
    6 Hoang