TY - JOUR
T1 - Fluorine-substituted ligands for the peroxisome proliferator-activated receptor gamma (PPARγ)
T2 - Potential imaging agents for metastatic tumors
AU - Kim, Sung Hoon
AU - Jonson, Stephanie D.
AU - Welch, Michael J.
AU - Katzenellenbogen, John A.
PY - 2001/5
Y1 - 2001/5
N2 - The peroxisome proliferator-activated receptor gamma (PPARγ), 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 PPARγ, we have synthesized two fluorine-substituted analogues of a high affinity ligand from the phenylpropanoic acid class. The analogue having the highest affinity for PPARγ 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 PPARγ 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.
AB - The peroxisome proliferator-activated receptor gamma (PPARγ), 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 PPARγ, we have synthesized two fluorine-substituted analogues of a high affinity ligand from the phenylpropanoic acid class. The analogue having the highest affinity for PPARγ 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 PPARγ 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.
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U2 - 10.1021/bc000153b
DO - 10.1021/bc000153b
M3 - Article
C2 - 11353543
AN - SCOPUS:0035011748
SN - 1043-1802
VL - 12
SP - 439
EP - 450
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 3
ER -