Purpose: 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. Experimental Design: 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. Results: 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 ¼ 3/group; P ¼ 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. Conclusions: 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.
|Original language||English (US)|
|Number of pages||10|
|Journal||Clinical Cancer Research|
|State||Published - Sep 15 2020|
Bibliographical noteFunding Information:
This work was supported by NIH/NCI R01 CA237272 (to A.M. LeBeau), NIH/ NCI R01 CA233562 (to A.M. LeBeau), a 2018 Prostate Cancer Foundation Challenge Award (to A.M. LeBeau), a 2013 Prostate Cancer Foundation Young Investigator Award (to A.M. LeBeau), and NIH/NCI T32 CA009138 (to H.M. Hintz). The authors acknowledge the University Imaging Centers at the University of Minnesota (Minneapolis, MN) for their technical advice and support of various imaging equipment. In particular, the authors thank Jason Mitchell for his PET/CT imaging assistance. We thank the University of Minnesota's Research Animal Resources staff for assisting with research animal maintenance and include a special thanks to Jason Austin for his help with injections and Yingming Li for her expertise with the IT model. The authors are grateful to Colleen Forster and the rest of the Biorepository and Laboratory Services Division at the University of Minnesota (Minneapolis, MN) for their histology and pathology support.
© 2020 American Association for Cancer Research.
Copyright 2021 Elsevier B.V., All rights reserved.
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Extramural
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