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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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anti-1-Amino-2-[18F]fluorocyclobutane-1-carboxylic acid

, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD

Created: ; Last Update: February 10, 2011.

Chemical name:anti-1-Amino-2-[18F]fluorocyclobutane-1-carboxylic acidimage 104179256 in the ncbi pubchem database
Abbreviated name:anti-2-[18F]FACBC
Agent category:Compound
Target:L-type amino acid transporter
Target category:Transporter
Method of detection:Positron emission tomography (PET)
Source of signal:18F
  • Checkbox In vitro
  • Checkbox Rodents
Click on the above structure for additional information in PubChem.



A variety of 11C- and 18F-labeled amino acids have been studied for potential use in positron emission tomography (PET) oncology (1, 2). Most brain tumors show an increased uptake of amino acids as compared with normal brain tissue (3). These amino acids are composed of naturally occurring amino acids, such as l-[11C]leucine, l-[11C]methionine, and l-[11C]tyrosine, and non-natural amino acids, such as [11C]aminoisobutyric acid, [11C]1-aminocyclopentane-1-carboxylic acid, and [11C]1-aminocyclobutane-1-carboxylic acid. 123I-Labeled amino acids are also used in imaging in oncology (4-6). The natural amino acids are taken up by tumor cells through an energy-independent L-type amino acid transporter system and retained in tumor cells because of their higher than normal metabolic pathways, including incorporation into proteins (4). l-[11C]Methionine and [18F]fluorotyrosine have been widely used in the detection of tumors, but are not approved by the FDA. On the other hand, the non-natural amino acids are not metabolized but are taken up through both the L-type transporter and the energy-dependent A-type transporter (7). Therefore, they can accumulate intracellularly in high concentrations. In this chapter, anti-1-Amino-2-[18F]fluorocyclobutane-1-carboxylic acid (anti-2-[18F]FACBC) was shown to have a high tumor/brain ratio (8). Therefore, anti-2-[18F]FACBC could be a useful tracer in PET tumor imaging.



Nucleophilic fluorination of syn-cyclic sulfamidate precursor with K[18F]F/Kryptofix2.2.2 and subsequent acidic hydrolysis and purification provided a radiosynthesis yield of 29.5 ± 5.4% (decay-corrected, n = 5) of anti-2-[18F]FACBC at the end of synthesis (8). A radiochemical purity of 99% was obtained. The total synthesis time was 85 min. The specific activity of anti-2-[18F]FACBC was not reported.

In Vitro Studies: Testing in Cells and Tissues


Yu et al. (8) showed that anti-2-[18F]FACBC entered rat 9L gliosarcoma tumor cells in culture with 3.3 ± 0.1% injected dose (ID)/5 × 105 cells (n = 3) at 30 min of incubation. anti-2-[18F]FACBC uptake into rat 9L gliosarcoma tumor cells in culture was reduced by 59%, 33%, and 73% by the presence of 10 mM 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (L-type transporter inhibitor), N-methyl-α-aminoisobutyric acid (A-type transporter inhibitor), and a mixture of alanine, cysteine, and serine (ACS), respectively. The data suggest that anti-2-[18F]FACBC is predominantly transported into 9L cells via both L-type and A-type amino acid transporters. On the other hand, anti-3-[18F]FACBC is predominantly an L-type transporter substrate.

Animal Studies



Ex vivo biodistribution studies of anti-2-[18F]FACBC were performed in rats (n = 4/group) implanted intracerebrally with 9L gliosarcoma (8). Accumulation of anti-2-[18F]FACBC in the tumors was 0.51, 0.66, 0.65, and 0.60% ID/g at 15, 30, 60, and 120 min after injection, respectively. The accumulation in the contralateral brain tissue was <0.04% ID/g at these time points. The tumor/brain ratios were 12, 17, 14, and 26 at 15, 30, 60, and 120 min, respectively. The accumulation in the heart, muscle, bone, liver, lung, and blood was low. anti-3-[18F]FACBC and [18F]FDG exhibited tumor/brain ratios of 6.6 and 0.84, respectively, at 60 min in the same tumor model (9). No blocking studies were performed.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.


Coleman R.E., Hoffman J.M., Hanson M.W., Sostman H.D., Schold S.C. Clinical application of PET for the evaluation of brain tumors. J Nucl Med. 1991;32(4):616–22. [PubMed: 2013802]
Kaschten B., Stevenaert A., Sadzot B., Deprez M., Degueldre C., Del Fiore G., Luxen A., Reznik M. Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med. 1998;39(5):778–85. [PubMed: 9591574]
Herholz K., Heiss W.D. Positron emission tomography in clinical neurology. Mol Imaging Biol. 2004;6(4):239–69. [PubMed: 15262239]
Jager P.L., Vaalburg W., Pruim J., de Vries E.G., Langen K.J., Piers D.A. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42(3):432–45. [PubMed: 11337520]
Langen K.J., Pauleit D., Coenen H.H. 3-[(123)I]Iodo-alpha-methyl-L-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol. 2002;29(6):625–31. [PubMed: 12234586]
Lahoutte T., Caveliers V., Camargo S.M., Franca R., Ramadan T., Veljkovic E., Mertens J., Bossuyt A., Verrey F. SPECT and PET amino acid tracer influx via system L (h4F2hc-hLAT1) and its transstimulation. J Nucl Med. 2004;45(9):1591–6. [PubMed: 15347729]
Palacin M., Estevez R., Bertran J., Zorzano A. Molecular biology of mammalian plasma membrane amino acid transporters. Physiol Rev. 1998;78(4):969–1054. [PubMed: 9790568]
Yu W., Williams L., Camp V.M., Olson J.J., Goodman M.M. Synthesis and biological evaluation of anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid (anti-2-[18F]FACBC) in rat 9L gliosarcoma. Bioorg Med Chem Lett. 2010;20(7):2140–3. [PubMed: 20207538]
Shoup T.M., Olson J., Hoffman J.M., Votaw J., Eshima D., Eshima L., Camp V.M., Stabin M., Votaw D., Goodman M.M. Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors. J Nucl Med. 1999;40(2):331–8. [PubMed: 10025843]
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