TY - JOUR
T1 - CEACAM5-Targeted Immuno-PET in Androgen Receptor-Negative Prostate Cancer
AU - Imberti, Cinzia
AU - De Gregorio, Roberto
AU - Korsen, Joshua A.
AU - Hoang, Tran T.
AU - Khitrov, Samantha
AU - Kalidindi, Teja
AU - Nandakumar, Subhiksha
AU - Park, Jooyoung
AU - Zaidi, Samir
AU - Pillarsetty, Naga Vara Kishore
AU - Lewis, Jason S.
N1 - Publisher Copyright:
© 2024 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2024/7/1
Y1 - 2024/7/1
N2 - 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.
AB - 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.
KW - androgen receptor–negative prostate cancer
KW - CEACAM5
KW - immuno-PET
KW - molecular imaging
UR - http://www.scopus.com/inward/record.url?scp=85198023664&partnerID=8YFLogxK
U2 - 10.2967/jnumed.123.267107
DO - 10.2967/jnumed.123.267107
M3 - Article
C2 - 38782457
AN - SCOPUS:85198023664
SN - 1535-5667
VL - 65
SP - 1043
EP - 1050
JO - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
IS - 7
ER -
