Dataset Information

High fibroblast-activation-protein expression in castration-resistant prostate cancer supports the use of FAPI-molecular theranostics.

ABSTRACT:

Purpose

To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [⁶⁸ Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC).

Methods

Tissue microarrays (TMAs) were constructed from prostatic tissue from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and neuroendocrine PC (NEPC)) and were stained with anti-FAP monoclonal antibody. A positive pixel count algorithm (H-Index) was used to compare FAP expression between the groups. Additionally, three men with advanced CRPC or NEPC underwent [⁶⁸ Ga]Ga-FAPI-04 PET/CT, and PET positivity was analyzed.

Results

The mean H-index for benign tissue, primary PC, neoadjuvant androgen deprivation therapy before radical prostatectomy, CRPC, and NEPC was 0.018, 0.031, 0.042, 0.076, and 0.051, respectively, indicating a significant rise in FAP expression with advancement of disease. Corroborating these findings [⁶⁸ Ga]Ga-FAPI-04 PET/CT was highly positive in men with advanced CRPC.

Conclusion

Increased FAP tissue expression supports the use of FAP inhibitor (FAPI)-molecular theranostics in CRPC.

SUBMITTER: Kesch C

PROVIDER: S-EPMC8712308 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

High fibroblast-activation-protein expression in castration-resistant prostate cancer supports the use of FAPI-molecular theranostics.

Kesch Claudia C Yirga Leubet L Dendl Katharina K Handke Analena A Darr Christopher C Krafft Ulrich U Radtke Jan Philipp JP Tschirdewahn Stephan S Szarvas Tibor T Fazli Ladan L Gleave Martin M Giesel Frederik L FL Haberkorn Uwe U Hadaschik Boris B

European journal of nuclear medicine and molecular imaging 20210705 1

<h4>Purpose</h4>To evaluate fibroblast-activation-protein (FAP) expression in different clinical stages of prostate cancer (PC) with regards to utility of [<sup>68</sup> Ga]Ga-FAPI-04 PET/CT imaging in patients with castration-resistant PC (CRPC).<h4>Methods</h4>Tissue microarrays (TMAs) were constructed from prostatic tissue from 94 patients at different stages of PC (primary PC, patients undergoing neoadjuvant androgen deprivation therapy, CRPC, and neuroendocrine PC (NEPC)) and were stained w ...[more]

PMID: 34226953

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Project description:Heart failure remains a major source of late morbidity and mortality after myocardial infarction (MI). The temporospatial presence of activated fibroblasts in the injured myocardium predicts the quality of cardiac remodeling after MI. Therefore, monitoring of activated fibroblasts is of great interest for studying cardiac remodeling after MI. Fibroblast activation protein (FAP) expression is upregulated in activated fibroblasts. This study investigated the feasibility of imaging activated fibroblasts with a new 68Ga-labeled FAP inhibitor (68Ga-FAPI-04) for PET imaging of fibroblast activation in a preclinical model of MI. Methods: MI and sham-operated rats were scanned with 68Ga-FAPI-04 PET/CT (1, 3, 6, 14, 23, and 30 d after MI) and with 18F-FDG (3 d after MI). Dynamic 68Ga-FAPI-04 PET and blocking studies were performed on MI rats 7 d after coronary ligation. After in vivo scans, the animals were euthanized and their hearts harvested for ex vivo analyses. Cryosections were prepared for autoradiography, hematoxylin and eosin (H&E), and immunofluorescence staining. Results: 68Ga-FAPI-04 uptake in the injured myocardium peaked on day 6 after coronary ligation. The tracer accumulated intensely in the MI territory, as identified by decreased 18F-FDG uptake and confirmed by PET/MR and H&E staining. Autoradiography and H&E staining of cross-sections revealed that 68Ga-FAPI-04 accumulated mainly at the border zone of the infarcted myocardium. In contrast, there was only minimal uptake in the infarct of the blocked rats, comparable to the uptake in the remote noninfarcted myocardium (PET image-derived ratio of infarct uptake to remote uptake: 6 ± 2). Immunofluorescence staining confirmed the presence of FAP-positive myofibroblasts in the injured myocardium. Morphometric analysis of the whole-heart sections demonstrated 3- and 8-fold higher FAP-positive fibroblast density in the border zone than in the infarct center and remote area, respectively. Conclusion: 68Ga-FAPI-04 represents a promising radiotracer for in vivo imaging of post-MI fibroblast activation. Noninvasive imaging of activated fibroblasts may have significant diagnostic and prognostic value, which could aid clinical management of patients after MI.

Dataset Information

High fibroblast-activation-protein expression in castration-resistant prostate cancer supports the use of FAPI-molecular theranostics.

Purpose

Methods

Results

Conclusion

Publications

High fibroblast-activation-protein expression in castration-resistant prostate cancer supports the use of FAPI-molecular theranostics.

Similar Datasets

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