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

McConathy, Jonathan; Goodman, Mark M.

doi:10.1007/s10555-008-9154-7

Cited by 109 publications

(97 citation statements)

References 152 publications

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“…In 9L cells, this new tracer showed a linear increasing uptake and reached a maximum of 15.7 6 1.0 percentage injected dose (%ID) per 100 mg of protein at 120 min. This value is comparable to or a little higher than that reported for 18 F-FACBC (1-amino-3-18 F-fluorocyclobutanecarboxylic acid), another 18 F-labeled amino acid for tumor imaging developed under a totally different uptake mechanism (18,20,21). In SF188 cells, uptake of 18 F-(2S,4R)4-fluoroglutamine exhibited different kinetics from those in 9L cells and reached maximum around 60 min and then decreased.…”

Section: In Vitro Cell Uptake Studiessupporting

confidence: 71%

“…The rodents were sacrificed 30 min after injection, and the tumors were removed (3 separate m/tomND tumors were removed from 3 separate mice, and 2 9L tumors were processed from F344 rats). Tumors were separately homogenized in 1 mL of phosphate-buffered saline (containing 0.90 mM of Ca 21 and 1.05 mM of Mg 21 ) with a Wheaton overhead stirrer and centrifuged at 18,000g for 6 min. Layers were separated and counted with a g-counter (Cobra II; Packard) (0.5 min/sample, 80% efficiency).…”

Section: In Vivo Metabolism Studies In Transgenic Mice With M/tomnd Smentioning

confidence: 99%

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PET Imaging of Glutaminolysis in Tumors by ¹⁸F-(2S,4R)4-Fluoroglutamine

Lieberman

Plöessl²,

Wang³

et al. 2011

J Nucl Med

156

183

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Changes in gene expression, metabolism, and energy requirements are hallmarks of cancer growth and self-sufficiency. Upregulation of the PI3K/Akt/mTor pathway in tumor cells has been shown to stimulate aerobic glycolysis, which has enabled 18 F-FDG PET tumor imaging. However, of the millions of 18 F-FDG PET scans conducted per year, a significant number of malignant tumors are 18 F-FDG PET-negative. Recent studies suggest that several tumors may use glutamine as the key nutrient for survival. As an alternative metabolic tracer for tumors, 18 F-(2S,4R)4-fluoroglutamine was developed as a PET tracer for mapping glutaminolytic tumors. Methods: A series of in vitro cell uptake and in vivo animal studies were performed to demonstrate tumor cell addiction to glutamine. Cell uptake studies of this tracer were performed in SF188 and 9L glioblastoma tumor cells. Dynamic small-animal PET studies of 18 F-(2S,4R)4-fluoroglutamine were conducted in 2 animal models: xenografts produced in F344 rats by subcutaneous injection of 9L tumor cells and transgenic mice with M/tomND spontaneous mammary gland tumors. Results: In vitro studies showed that both transformed 9L and SF188 tumor cells displayed a high rate of glutamine uptake (maximum uptake, 16% dose/100 mg of protein). The cell uptake of 18 F-(2S,4R)4-fluoroglutamine by SF188 cells is comparable to that of 3 H-L-glutamine but higher than that of 18 F-FDG. The tumor cell uptake can be selectively blocked. Biodistribution and PET studies showed that 18 F-(2S,4R)4-fluoroglutamine localized in tumors with a higher uptake than in surrounding muscle and liver tissues. Data suggest that certain tumor cells may use glutamine for energy production. Conclusion: The results support that 18 F-(2S,4R)4-fluoroglutamine is selectively taken up and trapped by tumor cells. It may be useful as a novel metabolic tracer for tumor imaging.

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Section: In Vitro Cell Uptake Studiessupporting

confidence: 71%

Section: In Vivo Metabolism Studies In Transgenic Mice With M/tomnd Smentioning

confidence: 99%

PET Imaging of Glutaminolysis in Tumors by ¹⁸F-(2S,4R)4-Fluoroglutamine

Lieberman

Plöessl²,

Wang³

et al. 2011

J Nucl Med

156

183

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“…These include L-11 C-methionine, L-18 F-fluoro-a-methyl-tyrosine, O-(2-18 F-fluoro-ethyl) tyrosine, and anti-1-amino-3-18 F-fluorocyclobutyl-carboxylic acid (FACBC) (29)(30)(31)(32)(33). Uptake of these tracers permits imaging of primary and metastatic tumors and is likely related to the increased expression of amino acid transporters in tumors.…”

Section: Discussionmentioning

confidence: 99%

Preparation and Characterization of l-[5-¹¹C]-Glutamine for Metabolic Imaging of Tumors

Qü¹,

Oya²,

Lieberman³

et al. 2011

J Nucl Med

116

130

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Recently, there has been a renewed interest in the study of tumor metabolism above and beyond the Warburg effect. Studies on cancer cell metabolism have provided evidence that tumor-specific activation of signaling pathways, such as the upregulation of the oncogene myc, can regulate glutamine uptake and its metabolism through glutaminolysis to provide the cancer cell with a replacement of energy source. Methods: We report a convenient procedure to prepare L-[5-11 C]-glutamine. The tracer was evaluated in 9L and SF188 tumor cells (glioma and astrocytoma cell lines). The biodistribution of L-[5-11 C]-glutamine in rodent tumor models was investigated by dissection and PET. Results: By reacting 11 C-cyanide ion with protected 4-iodo-2-amino-butanoic ester, the key intermediate was obtained in good yield. After hydrolysis with trifluoroacetic and sulfonic acids, the desired optically pure L-[5-11 C]-glutamine was obtained (radiochemical yield, 5% at the end of synthesis; radiochemical purity, .95%). Tumor cell uptake studies showed maximum uptake of L-[5-11 C]-glutamine reached 17.9% and 22.5% per 100 mg of protein, respectively, at 60 min in 9L and SF188 tumor cells. At 30 min after incubation, more than 30% of the activity appeared to be incorporated into cellular protein. Biodistribution in normal mice showed that L-[5-11 C]-glutamine had significant pancreas uptake (7.37 percentage injected dose per gram at 15 min), most likely due to the exocrine function and high protein turnover within the pancreas. Heart uptake was rapid, and there was 3.34 percentage injected dose per gram remaining at 60 min after injection. Dynamic small-animal PET studies in rats bearing xenografted 9L tumors and in transgenic mice bearing spontaneous mammary gland tumors showed a prominent tumor uptake and retention. Conclusion: The data demonstrated that this tracer was favorably taken up in the tumor models. The results suggest that L-[5-11 C]-glutamine might be useful for probing in vivo tumor metabolism in glutaminolytic tumors.

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“…Radiolabeled aromatic amino acids are mostly tyrosine or phenylalanine analogs, and are primarily system L substrates, including 2-18 F-fluoro-L-tyrosine ( 18 F-TYR), L-3-18 F-alpha-methyl tyrosine ( 18 F-FMT), O-(2-18 F-Fluoroethyl)-l-tyrosine ( 18 F-FET), and 6-18 F-fluoro-L-3,4-dihydroxyphenylalanine ( 18 F-FDOPA) [19]. FET and FDOPA have been extensively evaluated in humans.…”

Section: Synthetic Amino Acidsmentioning

confidence: 99%

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

Zhu

Shim

2011

Nucl Med Mol Imaging

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Molecular imaging is one of the fastest growing areas of medical imaging. Positron emission tomography (PET) has been widely used in the clinical management of patients with cancer. Nuclear imaging provides biological information at the cellular, subcellular, and molecular level in living subjects with noninvasive procedures. In particular, PET imaging takes advantage of traditional diagnostic imaging techniques and introduces positron-emitting probes to determine the expression of indicative molecular targets at different stages of cancer. 18 F-fluorodeoxyglucose ( 18 F-FDG), the only FDA approved oncological PET tracer, has been widely utilized in cancer diagnosis, staging, restaging, and even monitoring response to therapy; however, 18 F-FDG is not a tumor-specific PET tracer. Over the last decade, many promising tumor-specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current non-18 F-FDG PET tracers in oncology that have been developed based on tumor characteristics such as increased metabolism, hyperproliferation, angiogenesis, hypoxia, apoptosis, and tumor-specific antigens and surface receptors.

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

Cited by 109 publications

References 152 publications

PET Imaging of Glutaminolysis in Tumors by ¹⁸F-(2S,4R)4-Fluoroglutamine

PET Imaging of Glutaminolysis in Tumors by ¹⁸F-(2S,4R)4-Fluoroglutamine

Preparation and Characterization of l-[5-¹¹C]-Glutamine for Metabolic Imaging of Tumors

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

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

Cited by 109 publications

References 152 publications

PET Imaging of Glutaminolysis in Tumors by 18F-(2S,4R)4-Fluoroglutamine

PET Imaging of Glutaminolysis in Tumors by 18F-(2S,4R)4-Fluoroglutamine

Preparation and Characterization of l-[5-11C]-Glutamine for Metabolic Imaging of Tumors

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

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Product

Resources

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PET Imaging of Glutaminolysis in Tumors by ¹⁸F-(2S,4R)4-Fluoroglutamine

PET Imaging of Glutaminolysis in Tumors by ¹⁸F-(2S,4R)4-Fluoroglutamine

Preparation and Characterization of l-[5-¹¹C]-Glutamine for Metabolic Imaging of Tumors