Synthesis of a nonpeptide carbon-11 labeled substance P antagonist for PET studies.
CP 96,345 is a nonpeptide high affinity antagonist of the substance P (NK1) receptor. The radiosynthesis of [11C]CP 96,345 suitable for Positron Emission Tomography (PET) applications is described. [11C]CP 96,345 was prepared by O-methylation of a desmethyl precursor via in situ generation of its phenolate salt. The in vivo tissue distribution of [11C]CP 96,345 in guinea pigs (n = 2) at 5 and 30 min was determined. Uptake was low in brain (approximately 0.04% dose/g) and highest (approximately 1-2% dose/g) in the spleen and lungs. The present findings indicate that the use of [11C]CP 96,345 in PET might be more applicable to the study of substance P receptors in peripheral tissues involved with inflammatory disease and arthritis.
Del Rosario
R B
RB
Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028.
Mangner
T J
TJ
Gildersleeve
D L
DL
Shreve
P D
PD
Weiland
D M
DM
Lowe
J A
JA
Drozda
S E
SE
Snider
R M
RM
D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D006168:Guinea Pigs; D007553:Isotope Labeling / Q000379:methods; D008954:Models, Biological; D013373:Substance P / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D001713:Biphenyl Compounds; D002250:Carbon Radioisotopes; D013373:Substance P; C066892:CP 96345