Carbon-11 labeled ethionine and propionine as tumor detecting agents.
To develop 18F-fluoroalkyl derivatives of methionine (MET) as a tumor detecting agent by mean of clinical PET, a pilot study assessing the potential of their parent compounds, 11C-labeled ethionine (11C-ETH) and propionine (11C-PRO), was performed. 11C-ETH and 11C-PRO were prepared by the reaction of L-homocysteine thiolactone and corresponding 11C-alkyl iodides. After i.v. injection of a mixture of 3H-MET. 14C-ETH and 11C-PRO into mice bearing FM3A mammary carcinoma, the highest FM3A uptake was found in 14C-ETH, followed by 3H-MET and 11C-PRO, while the FM3A-to-brain and FM3A-to-muscle ratios were nearly the same for all three compounds. The FM3A uptake of 14C-ETH and 11C-PRO were nearly equal or slightly higher than the liver uptake. In the pancreas, liver, FM3A and brain tissues, incorporation of 14C-ETH into acid-precipitable materials was much lower than that of 3H-MET, whereas no incorporation of 11C-PRO was found. Brain uptake of all three compounds was significantly reduced by carrier MET-loading (5 min p.i.) or by cycloheximide treatment to inhibit protein synthesis (60 min p.i.), whereas the FM3A uptake was not affected. Incorporation of 14C-ETH into acid-precipitable materials was inhibited by the cycloheximide. The results suggest that 11C-labeled ETH has a similar potential for tumor detection by PET as 11C-MET, and that 11C-PRO has similar properties to those of other artificial amino acids. The development of 18F-fluoroalkyl derivatives of MET is of interest as the next step.
Ishiwata
K
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan. ishiwata@pet.tmig.or.jp
Kasahara
C
C
Hatano
K
K
Ishii
S
S
Senda
M
M
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002087:Butyrates / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003513:Cycloheximide / Q000494:pharmacology; D005001:Ethionine / Q000493:pharmacokinetics; D005260:Female; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D008715:Methionine / Q000493:pharmacokinetics; D051379:Mice; D010865:Pilot Projects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002087:Butyrates; D002250:Carbon Radioisotopes; D011500:Protein Synthesis Inhibitors; D006710:Homocysteine; C107759:propionine; D003513:Cycloheximide; D008715:Methionine; D005001:Ethionine