Synthesis and evaluation of 15-(4-(2-[¹⁸F]Fluoroethoxy)phenyl)pentadecanoic acid: a potential PET tracer for studying myocardial fatty acid metabolism.
15-(4-(2-[¹⁸F]fluoroethoxy)phenyl)pentadecanoic acid ([¹⁸F]7) was synthesized as a PET probe for assessing myocardial fatty acid metabolism. The radiosynthesis of [¹⁸F]7 was accomplished using a two-step reaction, starting with the corresponding tosylate ester, methyl 15-(4-(2-(tosyloxy)ethoxy)phenyl)pentadecanoate (5), and gave the radiolabeled fatty acid, [¹⁸F]7 in a radiolabeling yield of 55-60% and a specific activity of >2000 Ci/mmol (decay corrected to EOB). The biological evaluation of [¹⁸F]7 in rats displayed high uptake in heart (1.94%ID/g at 5 min), which was higher than the uptake (%ID/g) in blood, lung, muscle, pancreas, and brain. MicroPET studies of [¹⁸F]7 in Sprague-Dawley rats demonstrated excellent images of the myocardium when compared with [¹¹C]palmitate images in the same animal. Moreover, the tracer kinetics of [¹⁸F]7 paralleled those seen with [¹¹C]palmitate, with an early peak followed by biphasic washout. When compared to [¹¹C]palmitate, [¹⁸F]7 exhibited a slower early clearance (0.17 ± 0.01 vs 0.30 ± 0.02, P < 0.0001) and a significantly higher late clearance (0.0030 ± 0.0005 vs 0.0006 ± 0.00013, P < 0.01). These initial studies suggest that [¹⁸F]7 could be a potentially useful clinical PET tracer to assess abnormal myocardial fatty acid metabolism.
Division of Radiological Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Zhude
Z
Tu
Shihong
S
Li
Terry L
TL
Sharp
Pilar
P
Herrero
Carmen S
CS
Dence
Robert J
RJ
Gropler
Robert H
RH
Mach
D000818:Animals; D002247:Carbon Isotopes / Q000737:chemistry / Q000378:metabolism; D005019:Ethyl Ethers / Q000737:chemistry / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D050356:Lipid Metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D019308:Palmitic Acid / Q000737:chemistry / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002247:Carbon Isotopes; D005019:Ethyl Ethers; D005227:Fatty Acids; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019308:Palmitic Acid; C117025:pentadecanoic acid