Evaluation of [1-11C]-?-aminoisobutyric acid for tumor detection and amino acid transport measurement: spontaneous canine tumor studies

The non-natural amino acid positron emission tomography tracers, 2-amino[3-11 C]isobutyric acid ([3-11 C] AIB) and 2-amino[ 11 C]methyl-isobutyric acid ([ 11 C]MeAIB), are metabolically stable in vivo and accumulate in tumors. [3-11 C]AIB is transported into cells mainly via the amino acid transport system A and partially via systems L and ASC, whereas [ 11 C]MeAIB is transported into cells specifically via system A. How transport via the different systems affects the tumor uptake of these tracers, however, is unclear. In the present study, the tumor uptake of the two tracers was directly compared in eight lung cancer models (A549, H82, H441, H460, H1299, H1650, PC14, and SY), and the correlation of tumor uptake with several factors (amino acid transporter expression, contribution of amino acid transport systems to AIB uptake and tumor proliferation indices) was analyzed. Biodistribution analyses revealed that the tumor uptake of [3-11 C]AIB (4.9 to 19.2% injected dose per gram [ID/g]) was higher than that of [ 11 C]MeAIB (3.1 to 15.9% ID/g) in all eight tumors, with a statistically significant difference in three tumors (P<0.01 in H441 and H460 tumors, P<0.05 in H82 tumors). A significant correlation was observed between the tumor uptake of the two tracers (r= 0.95, P<0.01). The mRNA expression levels of the amino acid transporters of system A (SLC38A1 and SLC38A2), system L (SLC7A5) and system ASC (SLC1A5) were higher in all eight tumors than in the normal lung, with widely varying expression patterns. Although the contributions of the amino acid transport systems, Ki-67 indices and tumor doubling times greatly differed among the eight models, these factors did not correlate with the tumor uptake of either tracer. The higher tumor uptake of [3-11 C]AIB and the correlation of tumor uptake between [3-11 C]AIB and [ 11 C]MeAIB warrant further investigation in clinical studies in order to clarify the role of [3-11 C]AIB PET in oncology imaging.

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“…2). Both tracers accumulated at low levels in the lungs and at high levels in the salivary glands, consistent with previous reports (6,13,23).…”

Section: Pet Imaging With [3-11 C]aib and [ 11 C]meaib In Tumor-bearisupporting

confidence: 92%

Direct comparison of 2‑amino[3‑11C]isobutyric acid and 2‑amino[11C]methyl‑isobutyric acid uptake in eight lung cancer xenograft models

et al. 2018

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“…Initial studies with radiolabeled AIB in animals including murine melanoma xenograft and canine spontaneous tumor models demonstrated uptake in some but not all tumors [187,188]. Studies of [ 11 C]AIB in a small number of patients with soft tissue sarcomas and melanoma showed good uptake in the majority of the known tumors [177,178,189].…”

Section: αα-Dialkyl Amino Acidsmentioning

confidence: 96%

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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“…Several groups have used radiolabeled AIB for tumor imaging in animal models of brain and systemic tumors, including rodents with implanted glioma, colon, melanoma, and prostate tumors as well canines with spontaneously occurring tumors . In these studies, AIB generally demonstrated good tumor imaging properties, although the uptake in the spontaneous canine tumors was variable.…”

Section: Fluorine‐18 and Radioiodinated αα‐Dialkyl Amino Acidsmentioning

confidence: 99%

Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents

McConathy

Jarkas

et al. 2011

Medicinal Research Reviews

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Radiohalogenated α-amino acids are a diverse and useful class tumor imaging agents suitable for positron emission tomography and single photon emission computed tomography. These tracers target the increased rates of amino acid transport exhibited by many tumor cells. The most established clinical use for radiolabeled amino acids is imaging primary and recurrent gliomas, and there is growing evidence that they may also be useful for other oncologic applications, including neuroendocrine tumors and prostate cancer. This review focuses on the synthesis, radiolabeling, and preclinical evaluation of three series of nonnatural radiohalogenated amino acids: alicyclic, α,α-dialkyl, and 1H-[1,2,3]triazole amino acids which target system L, system A, and cationic amino acid transport systems, respectively.

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Evaluation of [1-11C]-?-aminoisobutyric acid for tumor detection and amino acid transport measurement: spontaneous canine tumor studies

Cited by 19 publications

References 19 publications

Direct comparison of 2‑amino[3‑11C]isobutyric acid and 2‑amino[11C]methyl‑isobutyric acid uptake in eight lung cancer xenograft models

Direct comparison of 2‑amino[3‑11C]isobutyric acid and 2‑amino[11C]methyl‑isobutyric acid uptake in eight lung cancer xenograft models

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

Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents

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