Investigations into tumor accumulation and peroxisome proliferator activated receptor binding by F-18 and C-11 fatty acids.
[11C]Acetate, a myocardial PET imaging agent for analysis of oxidative metabolism, has potential use in tumor imaging. Aromatic fatty acids display antitumor effects with phenylacetate currently in clinical trial. Tumor differentiation and cytostasis resulting from phenylacetate treatment may involve the peroxisome proliferator-activated receptor alpha (PPARalpha). To examine whether aromatic fatty acids are potential imaging agents for PPARalpha or tumors in general, [11C]phenylacetic acid (PAA) and [18F]fluorophenyl-acetic acid (FPAA) were synthesized and evaluated in EMT-6 tumor bearing mice and 9L-Glioma tumor bearing rats and compared to [11C]acetate. [11C]Acetate showed better tumor accumulation than PAA or FPAA. The aromatic fatty acids did not directly bind PPARalpha as confirmed by a biodistribution study of PAA in PPARalpha -/- mice.
Jonson
Stephanie D
SD
Division of Radiological Sciences, Washington University School of Medicine, 510 South Kingshighway, St. Louis, MO 63110, USA.
Welch
Michael J
MJ
D000085:Acetates / Q000493:pharmacokinetics*; D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010648:Phenylacetates / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*
D000085:Acetates; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D010648:Phenylacetates; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C455112:2-(4-fluorophenyl)acetic acid; C025136:phenylacetic acid