Imaging of Fibroblast Activation Protein Alpha Expression in a Preclinical Mouse Model of Glioma Using Positron Emission Tomography.
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 [89Zr]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 (Ka) of 10-8 M-1 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.
['Pandya|Darpan N|DN|', 'Sinha|Akesh|A|', 'Yuan|Hong|H|', 'Mutkus|Lysette|L|0000-0002-7378-7137', 'Stumpf|Kristina|K|0000-0002-3422-5959', 'Marini|Frank C|FC|', 'Wadas|Thaddeus J|TJ|']
D000818:Animals D045744:Cell Line, Tumor D016543:Central Nervous System Neoplasms D010450:Endopeptidases D005260:Female D018093:Gelatinases D015972:Gene Expression Regulation, Neoplastic D005909:Glioblastoma D006801:Humans D008565:Membrane Proteins D051379:Mice D008819:Mice, Nude D009363:Neoplasm Proteins D009374:Neoplasms, Experimental D049268:Positron-Emission Tomography D012697:Serine Endopeptidases
fibroblast activation protein alpha glioma PET cancer Zirconium-89