Abstract
To explore their potential use as in vivo tracers, the uptake of the amino acids glutamine, glutamate and aspartate, labeled with 11C or 14C, was evaluated in tumor cell aggregates, in vivo in rats and a few pilot studies with positron emission tomography (PET) in patients. The uptake in aggregates increased linearly with time, and was competitively inhibited by the same amino acids. The uptake of 14C-glutamate in carcinoid cells (BON) was inhibited by cystine but not by aspartate, contrary to the result in neuroblastoma (LAN). 6-Diazo-oxy-L-norleucine (a glutamine analogue) and Substance P had different effect on the uptake of glutamate in different cells. The metabolic fate of 14C-glutamate was evaluated with protein separation and with HPLC. The in vivo distribution in rats showed the highest uptake of 11C-glutamine and 11C-glutamate in pancreas and kidney, and of 11C-aspartate in the lung. In the human studies with PET, pancreas had the highest uptake followed by kidney with 11C-glutamate, and followed by spleen with 11C-aspartate. A primary pancreas tumour and metastases in liver were difficult to identify except in one case.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Aminoadipic Acid / pharmacology
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Adenocarcinoma / diagnostic imaging
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Adenocarcinoma / secondary
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Animals
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Aspartic Acid / metabolism
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Aspartic Acid / pharmacokinetics*
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Biological Transport / drug effects
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Carbon Radioisotopes / metabolism
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Carbon Radioisotopes / pharmacokinetics*
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Carcinoid Tumor / diagnostic imaging
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Carcinoid Tumor / prevention & control
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Cell Aggregation
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Chromatography, High Pressure Liquid
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Diazooxonorleucine / pharmacology
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Glioma / metabolism
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Glioma / pathology
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Glutamic Acid / metabolism
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Glutamic Acid / pharmacokinetics*
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Glutamine / antagonists & inhibitors
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Glutamine / metabolism
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Glutamine / pharmacokinetics*
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Humans
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Liver Neoplasms / diagnostic imaging
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Liver Neoplasms / secondary
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Male
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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Neuroendocrine Tumors / diagnostic imaging
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Neuroendocrine Tumors / metabolism*
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Neuroendocrine Tumors / pathology
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Octreotide / pharmacology
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Pancreatic Neoplasms / diagnostic imaging
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Pilot Projects
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Radioactive Tracers
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Rats
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Rats, Sprague-Dawley
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Substance P / pharmacology
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Tissue Distribution
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Tomography, Emission-Computed*
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
Substances
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Carbon Radioisotopes
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Radioactive Tracers
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Diazooxonorleucine
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Glutamine
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2-Aminoadipic Acid
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Aspartic Acid
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Substance P
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Glutamic Acid
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Octreotide