Positron-emission tomography imaging of the TSPO with [(18)F]FEPPA in a preclinical breast cancer model.
The present study aims to image the 18-kDa translocator protein (TSPO; formerly known as the peripheral benzodiazepine receptor) in a preclinical human breast cancer (BC) xenograft mouse model with positron-emission tomography (PET). An automated radiosynthesis of [(18)F]-N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([(18)F]FEPPA) was validated for human use using a commercial synthesis module and resulted in a high radiochemical yield (30%±8%, uncorrected; n=54) and specific activity (6±4 Ci/μmol). Tumor uptake of [(18)F]FEPPA in mice bearing subcutaneous MDA-MB-231 BC xenografts was evaluated by PET-computed tomography imaging and ex vivo biodistribution studies. Although the tumor was successfully visualized, ex vivo biodistribution studies revealed low tumor uptake (0.7%ID/g), with the majority of radioactivity distributed in the spleen, muscle, and heart despite high TSPO expression in this cell line. Our laboratory routinely prepares [(18)F]FEPPA for human-imaging studies in the central nervous system, and we envision that radiopharmaceuticals that target the TSPO have the potential for imaging macrophages in the tumor microenvironment.
PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario. vasdev.neil@mgh.harvard.edu
Neil
N
Vasdev
David E
DE
Green
Douglass C
DC
Vines
Kristin
K
McLarty
Patrick N
PN
McCormick
Matthew D
MD
Moran
Sylvain
S
Houle
Alan A
AA
Wilson
Raymond M
RM
Reilly
D000813:Anilides / Q000493:pharmacokinetics; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods; D011725:Pyridines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000032:analysis* / Q000378:metabolism
D000813:Anilides; D005462:Fluorine Radioisotopes; C530438:N-(2-((N-(4-phenoxypyridin-3-yl)acetamido)methyl)phenoxy)ethyl fluoride; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human