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Medientyp:
E-Artikel
Titel:
Imaging Fibroblast Activation Protein Alpha Improves Diagnosis of Metastatic Prostate Cancer with Positron Emission Tomography
Beteiligte:
Hintz, Hallie M.;
Gallant, Joseph P.;
Vander Griend, Donald J.;
Coleman, Ilsa M.;
Nelson, Peter S.;
LeBeau, Aaron M.
Erschienen:
American Association for Cancer Research (AACR), 2020
Erschienen in:
Clinical Cancer Research, 26 (2020) 18, Seite 4882-4891
Sprache:
Englisch
DOI:
10.1158/1078-0432.ccr-20-1358
ISSN:
1078-0432;
1557-3265
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Purpose:</jats:title>
<jats:p>Metastatic castration-resistant prostate cancer (mCRPC) is a lethal, heterogeneous disease with few therapeutic strategies that significantly prolong survival. Innovative therapies for mCRPC are needed; however, the development of new therapies relies on accurate imaging to assess metastasis and monitor response. Standard imaging modalities for prostate cancer require improvement and there remains a need for selective and sensitive imaging probes that can be widely used in patients with mCRPC.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Experimental Design:</jats:title>
<jats:p>We evaluated the transmembrane protease fibroblast activation protein alpha (FAP) as a targetable cell surface antigen for mCRPC. Genomic and IHC analyses were performed to investigate FAP expression in prostate cancer. Our FAP-targeted antibody imaging probe, [89Zr]Zr-B12 IgG, was evaluated by PET/CT imaging in preclinical prostate cancer models.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>Analysis of patient data documented FAP overexpression in metastatic disease across tumor subtypes. PET imaging with [89Zr]Zr-B12 IgG demonstrated high tumor uptake and long-term retention of the probe in the preclinical models examined. FAP-positive stroma tumor uptake of [89Zr]Zr-B12 IgG was 5-fold higher than the isotype control with mean %ID/cc of 34.13 ± 1.99 versus 6.12 ± 2.03 (n = 3/group; P = 0.0006) at 72 hours. Ex vivo biodistribution corroborated these results documenting rapid blood clearance by 24 hours and high tumor uptake of [89Zr]Zr-B12 IgG by 72 hours.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions:</jats:title>
<jats:p>Our study reveals FAP as a target for imaging the tumor microenvironment of prostate cancer. Validation of [89Zr]Zr-B12 IgG as a selective imaging probe for FAP-expressing tumors presents a new approach for noninvasive PET/CT imaging of mCRPC.</jats:p>
</jats:sec>