TY - JOUR
T1 - Synthesis and evaluation of 15-(4-(2-[18F]Fluoroethoxy)phenyl) pentadecanoic Acid
T2 - A potential PET tracer for studying myocardial fatty acid metabolism
AU - Tu, Zhude
AU - Li, Shihong
AU - Sharp, Terry L.
AU - Herrero, Pilar
AU - Dence, Carmen S.
AU - Gropler, Robert J.
AU - Mach, Robert H.
PY - 2010/12/15
Y1 - 2010/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78650410901&partnerID=8YFLogxK
U2 - 10.1021/bc100343h
DO - 10.1021/bc100343h
M3 - Article
C2 - 21070001
AN - SCOPUS:78650410901
SN - 1043-1802
VL - 21
SP - 2313
EP - 2319
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 12
ER -