Synthesis and quality assurance of [11C]alpha-aminoisobutyric acid (AIB), a potential radiotracer for imaging and amino acid transport studies in normal and malignant tissues

Schmall, Bernard; Conti, Peter S.; Bigler, Rodney E.; Zanzonico, Pat; Dahl, Jan; Sundoro-Wu, Boby M.; Jacobsen, Jon K.; Lee, Richard

doi:10.1016/0047-0740(84)90001-9

Cited by 27 publications

(20 citation statements)

References 21 publications

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“…In contrast, the brain uptake of [ 18 F]FET, a well-established system L AAT substrate, ranged from 2.4±0.3 to 2.6±0.4 %ID/g in nude mice under similar experimental conditions [46], representing 2.5-3.5 fold higher uptake than [ 18 F] 1 and 7-14 fold higher uptake than [ 18 F] 2 . The low brain uptake of ( R )- and ( S )-[ 18 F] 1 and ( R )- and ( S )-[ 18 F] 2 is consistent with the earlier studies performed with [ 11 C]AIB [47] as well as with [ 18 F] 1 and [ 18 F] 2 in a rat orthotopic brain tumor model [35, 36]. Again in this rat model, the values of brain uptake of ( R )-[ 18 F] 1 , ( S )-[ 18 F] 1 , ( R )-[ 18 F] 2 , and ( S )-[ 18 F] 2 at 60 min were 0.1±0.02, 0.06±0.01, 0.05±0.02, and 0.05±0.01 %ID/g, respectively, and the brain uptake of system L substrate [ 18 F]FACBC was 0.26±0.03 %ID/g [48], showing a good correlation with the present study.…”

Section: Resultssupporting

confidence: 91%

System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid

Yu¹,

McConathy²,

Olson³

et al. 2015

Nuclear Medicine and Biology

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Introduction Amino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural 18F-labeled amino acids, (R)- and (S)-[18F]FAMP 1 and (R)- and (S)-[18F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo for their potential utility in brain and systemic tumor imaging based upon primarily system A transport with positron emission tomography (PET). Methods The transport of enantiomers of [18F]FAMP 1 and [18F]MeFAMP 2 was measured through in vitro uptake assays in human derived cancer cells including A549 (lung), DU145 (prostate), SKOV3 (ovary), MDA MB468 (breast) and U87 (brain) in the presence and absence of amino acid transporter inhibitors. The in vivo biodistribution of these tracers was evaluated using tumor mice xenografts at 15, 30, 60 and 120 min post injection. Results All four tracers showed moderate to high levels of uptake (1- 9 %ID/5×105 cells) by the cancer cell lines tested in vitro. AAT cell inhibition assays demonstrated that (R)-[18F]1 and (S)-[18F]1 entered these tumor cells via mixed AATs, likely but not limited to system A and system L. In contrast, (R)-[18F]2 and (S)-[18F]2 showed high selectivity for system A AAT. Similar to the results of in vitro cell studies, the tumor uptake of all four tracers was good to high and persisted over the 2 hours time course of in vivo studies. The accumulation of these tracers was higher in tumor than most normal tissues including blood, brain, muscle, bone, heart, and lung, and the tracers with the highest in vitro selectivity for system A AAT generally demonstrated the best tumor imaging properties. Higher uptake of these tracers was observed in the pancreas, kidney and spleen compared to tumors. Conclusions These preclinical studies demonstrate good imaging properties in a wide range of tumors for all four amino acids evaluated with (R)-[18F]2 having the highest selectivity for system A AAT.

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Section: Resultssupporting

confidence: 91%

System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid

Yu¹,

McConathy²,

Olson³

et al. 2015

Nuclear Medicine and Biology

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“…27 AIB, a nonmetabolized synthetic analogue of the natural amino acid alanine, reflects the alanine-like amino acid transport. 30 Labeled with carbon-11, it has been applied as a tumor imaging agent in animal models and patients with solid tumors (e.g., adenocarcinoma, malignant melanoma). 27,30 Results have indicated that AIB is suitable for imaging soft tissue sarcomas.…”

Section: Discussionmentioning

confidence: 99%

“…30 Labeled with carbon-11, it has been applied as a tumor imaging agent in animal models and patients with solid tumors (e.g., adenocarcinoma, malignant melanoma). 27,30 Results have indicated that AIB is suitable for imaging soft tissue sarcomas. 31 Its potential in low-grade soft tissue sarcomas and in the differentiation of inflammation is being evaluated.…”

Section: Discussionmentioning

confidence: 99%

Clinical Value of [18-F] Fluorodeoxyglucose Positron Emission Tomography Imaging in Soft Tissue Sarcomas

Schwarzbach¹,

Dimitrakopoulou-Strauß²,

Willeke³

et al. 2000

Annals of Surgery

166

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“…α-methyl leucine) would be expected to be a system L substrates. Radiosyntheses of [ 11 C]AIB have been described which incorporate carbon-11 in an α-methyl position or the carboxylate position [172][173][174], while labeling of [ 11 C] MeAIB has been performed with carbon-11 incorporated in an α-methyl or N-methyl position [175,176]. Both [ 11 C] AIB and [ 11 C]MeAIB can be prepared in good radiochemical yield and high specific activity.…”

Section: αα-Dialkyl Amino Acidsmentioning

confidence: 99%

Non-natural amino acids for tumor imaging using positron emission tomography and single photon emission computed tomography

McConathy

Goodman

2008

Cancer Metastasis Rev

109

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Amino acids are required nutrients for proliferating tumor cells, and amino acid transport is upregulated in many tumor types. Studies of radiolabeled amino acids in animals and humans demonstrate that amino acid based tracers have advantageous characteristics relative to 2-[(18)F]fluoro-2-deoxyglucose in certain tumors, particularly brain gliomas. Non-natural amino acids for tumor imaging generally have greater metabolic stability and can be labeled with longer-lived radionuclides for positron emission tomography and single photon emission computed tomography such as fluorine-18 and iodine-123. Amino acids enter cells via amino acid transport with varying selectivity based on their chemical structure. This review focuses on the rationale, biological basis, current status and future prospects of radiolabeled non-natural amino acids for tumor imaging and discusses various classes of these compounds including aromatic, alicyclic and alpha,alpha-dialkyl amino acids.

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Synthesis and quality assurance of [11C]alpha-aminoisobutyric acid (AIB), a potential radiotracer for imaging and amino acid transport studies in normal and malignant tissues

Cited by 27 publications

References 21 publications

System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid

System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid

Clinical Value of [18-F] Fluorodeoxyglucose Positron Emission Tomography Imaging in Soft Tissue Sarcomas

Non-natural amino acids for tumor imaging using positron emission tomography and single photon emission computed tomography

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