Fluorine-substituted ligands for the peroxisome proliferator-activated receptor gamma (PPARgamma): potential imaging agents for metastatic tumors.
The peroxisome proliferator-activated receptor gamma (PPARgamma), a primary regulator of lipid metabolism, is present in many tumor cell lines and animal tumor systems and, in some cases, can mediate effective antitumor therapy with potent synthetic ligands. In an approach to image tumors with positron-emission tomography (PET) based on their content of PPARgamma, we have synthesized two fluorine-substituted analogues of a high affinity ligand from the phenylpropanoic acid class. The analogue having the highest affinity for PPARgamma was labeled with the positron-emitting radionuclide fluorine-18. In tissue distribution studies in normal rats and in SCID mice bearing human breast tumor xenografts, this compound did not show evidence of receptor-mediated uptake. The prospects for using PPARgamma as a target for imaging tumors may be limited by the low receptor concentrations in tumors and by the pharmacokinetic behavior of this class of ligands, which appears to be more favorable for therapy than for imaging.
Kim
S H
SH
Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
Jonson
S D
SD
Welch
M J
MJ
Katzenellenbogen
J A
JA
D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000556:secondary*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008024:Ligands; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D005462:Fluorine Radioisotopes; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors