Synthesis of C-11-{beta}-aminoisobutyric acid (C-11-{beta}-AlB): A major in vivo catabolite of [methyl-C-11]thymidine
Journal Article
·
· Journal of Nuclear Medicine
OSTI ID:441622
- USC PET Imaging Science Center, Los Angeles, CA (United States)
Carbon-11 labeled thymidine (TdR) is being used for brain tumor imaging in patients with PET. Following clearance of 5-methyl C-11 TdR from plasma in humans, there is a progressive increase of C-11 activity in normal brain and tumor presumably secondary to accumulation of C-11 beta-AIB, a major by-product of thymidine catabolism in vivo. Canine studies have demonstrated that the major radiolabeled species in acid soluble extracts of brain and tumor tissues during C-14 TdR studies is beta-AIB. The previously reported synthesis of beta-AIB is not suitable for incorporation of carbon-11. A convenient method of synthesis of C-11 beta-AIB was developed where commercially available beta-alanine ethyl ester was converted to the cold precursor reagent, benzaldimine-beta-alanine ethyl ester, in 87% yield. Treatment of the imine derivative with LDA (1.1 eq) in THF at -78{degrees} C, followed by addition of iodomethane (1.1 eq) produced the alpha-methylated benzaldimine-beta-alanine ethyl ester in 73% chemical yield. Deprotection of the amino group by acidic hydrolysis followed by basic hydrolysis of the ester group produced the desired product in 50% chemical yield. Chemical structures of unlabeled intermediates and product were confirmed by H-1 NMR and CI mass spectrometry. Labeling was accomplished using C-11-methyl iodide prepared from C-11-CO{sub 2} according to literature methods. After removal of protecting groups and neutralization, the enatiomeric mixture was purified by HPLC using a semipreparative reverse phase C-18 column and PBS as eluent. The desired compound was eluted at 8.26 minutes. In preliminary runs, the synthesis time was 39 minutes including HPLC purification, with radiochemical yields of 5-6% (EOB). Radiochemical purity was >99%
- OSTI ID:
- 441622
- Report Number(s):
- CONF-950603--
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 36; ISSN 0161-5505; ISSN JNMEAQ
- Country of Publication:
- United States
- Language:
- English
Similar Records
Development of (/sup 11/C)-. cap alpha. -aminoisobutyric acid and (/sup 18/F)-haloperidol as substrate-specific radiotracers
Synthesis of 3-(C-11-methyl)-nifedipine, a potent Ca/sup ++/ channel antagonist, for positron emission tomography
Enzymatic syntheses of (1-(C-11))pyruvic acid and L-(1-(C-11))lactic acid via DL-(1-(C-11))alanine
Thesis/Dissertation
·
Thu Dec 31 23:00:00 EST 1981
·
OSTI ID:5212462
Synthesis of 3-(C-11-methyl)-nifedipine, a potent Ca/sup ++/ channel antagonist, for positron emission tomography
Conference
·
Sat Dec 31 23:00:00 EST 1983
· J. Nucl. Med.; (United States)
·
OSTI ID:6842988
Enzymatic syntheses of (1-(C-11))pyruvic acid and L-(1-(C-11))lactic acid via DL-(1-(C-11))alanine
Conference
·
Sat Dec 31 23:00:00 EST 1983
· J. Nucl. Med.; (United States)
·
OSTI ID:6758931