Imaging of Fibroblast Activation Protein Alpha Expression in a Preclinical Mouse Model of Glioma Using Positron Emission Tomography

Darpan N Pandya; Akesh Sinha; Hong Yuan; Lysette Mutkus; Kristina Stumpf; Frank C Marini; Thaddeus J Wadas

doi:10.3390/molecules25163672

Back

Imaging of Fibroblast Activation Protein Alpha Expression in a Preclinical Mouse Model of Glioma Using Positron Emission Tomography

Journal article

Open access

Peer reviewed

Imaging of Fibroblast Activation Protein Alpha Expression in a Preclinical Mouse Model of Glioma Using Positron Emission Tomography

Darpan N Pandya, Akesh Sinha, Hong Yuan, Lysette Mutkus, Kristina Stumpf, Frank C Marini and Thaddeus J Wadas

Molecules (Basel, Switzerland), Vol.25(16), p.3672

08/12/2020

DOI: 10.3390/molecules25163672

PMCID: PMC7464128

PMID: 32806623

Files and links (1)

url

https://doi.org/10.3390/molecules25163672View

Published (Version of record) Open Access

Abstract

Glioblastoma multiforme (GBM) is the most aggressive glioma of the primary central nervous system. Due to the lack of effective treatment options, the prognosis for patients remains bleak. Fibroblast activation protein alpha (FAP), a 170 kDa type II transmembrane serine protease was observed to be expressed on glioma cells and within the glioma tumor microenvironment. To understand the utility of targeting FAP in this tumor type, the immuno-PET radiopharmaceutical [ Zr]Zr-Df-Bz-F19 mAb was prepared and Lindmo analysis was used for its in vitro evaluation using the U87MG cell line, which expresses FAP endogenously. Lindmo analysis revealed an association constant (K ) of 10 M and an immunoreactivity of 52%. Biodistribution studies in U87MG tumor-bearing mice revealed increasing radiotracer retention in tumors over time, leading to average tumor-to-muscle ratios of 3.1, 7.3, 7.2, and 8.3 at 2, 24, 48 and 72 h, respectively. Small animal PET corroborated the biodistribution studies; tumor-to-muscle ratios at 2, 24, 48, and 72 h were 2.0, 5.0, 6.1 and 7.8, respectively. Autoradiography demonstrated accumulated activity throughout the interior of FAP tumors, while sequential tumor sections stained positively for FAP expression. Conversely, FAP tissues retained minimal radioactivity and were negative for FAP expression by immunohistochemistry. These results demonstrate FAP as a promising biomarker that may be exploited to diagnose and potentially treat GBM and other neuroepithelial cancers.

Animals

Cell Line, Tumor

Central Nervous System Neoplasms - diagnostic imaging

Central Nervous System Neoplasms - metabolism

Female

Gelatinases - biosynthesis

Gene Expression Regulation, Neoplastic

Glioblastoma - diagnostic imaging

Glioblastoma - metabolism

Humans

Membrane Proteins - biosynthesis

Mice

Mice, Nude

Neoplasm Proteins - biosynthesis

Neoplasms, Experimental - diagnostic imaging

Neoplasms, Experimental - metabolism

Positron-Emission Tomography

Serine Endopeptidases - biosynthesis

Details

Title: Subtitle: Imaging of Fibroblast Activation Protein Alpha Expression in a Preclinical Mouse Model of Glioma Using Positron Emission Tomography
Creators: Darpan N Pandya - University of Iowa
Akesh Sinha - University of Iowa
Hong Yuan - University of North Carolina at Chapel Hill
Lysette Mutkus - Wake Forest Institute for Regenerative Medicine
Kristina Stumpf - Wake Forest Institute for Regenerative Medicine
Frank C Marini - Wake Forest Institute for Regenerative Medicine
Thaddeus J Wadas - University of Iowa
Resource Type: Journal article
Publication Details: Molecules (Basel, Switzerland), Vol.25(16), p.3672
DOI: 10.3390/molecules25163672
PMID: 32806623
PMCID: PMC7464128
NLM abbreviation: Molecules
ISSN: 1420-3049
eISSN: 1420-3049
Grant note: W81XWH-13-1-0125 / Department of Defense P30 CA086862 / NCI NIH HHS CA219899-03 / NIH HHS
Language: English
Date published: 08/12/2020
Academic Unit: Radiology; Radiation Oncology
Record Identifier: 9984312964702771

Metrics

29 Record Views

30 Times Cited - Web of Science