Comparison of L-[1-11C]methionine and L-methyl-[11C]methionine for measuring in vivo protein synthesis rates with PET.

To evaluate the feasibility of using either L-[1-11C]-methionine or L-[methyl-11C]methionine for measuring protein synthesis rates by positron emission tomography (PET) in normal and neoplastic tissues, distribution and metabolic studies with 14C- and 11C-labeled methionines were carried out in rats bearing Walker 256 carcinosarcoma. The tissue distributions of the two 14C-labeled methionines were similar except for liver tissue. Similar distribution patterns were observed in vivo by PET using 11C-labeled methionines. The highest 14C incorporation rate into the protein-bound fraction was found in the liver followed by tumor, brain, and pancreas. The incorporation rates in liver and pancreas were different for the two methionines. By chloroform-methanol fractionation of these four tissues, in liver significantly different amounts of 14C were observed in macromolecules. Also in brain tissue slight differences were found. By HPLC analyses of the protein-free fractions of plasma, tumor, and brain tissue at 60 min after injection, for both methionines several 14C-labeled metabolites in different amounts, were detected. About half of the 14C-labeled material in the protein-free fraction was found to be methionine. In these three tissues the amount of nonprotein metabolites and [14C]bicarbonate amount ranged from 10% to 17% and 12% to 15% for L-[1-14C]methionine and L-[methyl-14C]methionine, respectively. From these results it can be concluded that the minor metabolic pathways have to be investigated in order to quantitatively model the protein synthesis by PET.

Reevaluation of triethers as markers for triglycerides during gastric emptying.

The validity of using triethers as markers for triglycerides during gastric emptying was investigated. Rats were given a lipid mixture containing [75Se]triether plus [131I]triolein or [3H]triether plus [14C]triolein intragastrically. Similar studies were performed on humans using a homogenized test meal to which was added [75Se]triether plus corn oil. Analysis of gastric contents at various time intervals after administration of the test meal did not show evidence of separation of triglyceride and triether in the stomach. It is discussed that the disappointing results of other workers using [3H]triether may be due to an artifact associated with instability of the tritium-to-triether bond in the preparation used.

Estimation of fat absorption from single fecal specimens using 131I-triolein and 75Se-triether. A study in rats with and without induced steatorrhea.

The simultaneous use of 131I-triolein and 75Se-triether, a nonabsorbable marker, in a single oral dose to estimate fat absorption from incomplete fecal collections was tested in rats with and without induced steatorrhea. The results in normal rats showed that analysis of single stool samples allows a valid estimate of fat absorption as defined by the balance study based on the total fecal recovery of 131I. However, in the few normal rats with poor absorption, the absorption values from successively excreted stools showed a tendency to increase. Similar findings were obtained from biliary fistula rats with marked steatorrhea. No evidence of different intestinal transit rates of test fat and marker was observed in bile-diverted rats, thus suggesting that the observed inconsistency in fat absorption values from different stool specimens reflects intraprandial differences in the absorption of fat. Studies on rats subjected to intestinal ischemia do not support the suggestion of others that separation of fat and triether will occur if a mucosal defect is involved as the cause of fat malabsorption. It is concluded that this dual isotope technique may be of value in the clinical estimation of fat absorption, as it offers important technical advantages over conventional fat balance studies.

Properties of glycerol-75Se-triether: A lipid-soluble marker for the estimation of intestinal fat absorption.

The properties of a 75Se-labeled glycerol triether were investigated in rat experiments designed to test this substance as a nonabsorbable marker for the assessment of intestinal fat absorption. After oral administration of 75Se-triether, the radioactivity was excreted almost completely with the feces. Amounts in excess of the quantity required tor clinical use did not interfere with overall fat absorption. No evidence for toxicity of 75Se-triether was observed. 131l-triolein was used as tracer fat and fat absorption was calculated by the following methods: (1) isotope balance method-oral intake minus fecal excretion of 131L; (2) isotope ratio method-comparison of the 131L to 75Se ratios in the test dose and in a stool sample. Results obtained from the isotope ratio method were in close agreement with those of the isotope balance method over a range of fat absorption of 80 to 95 per cent, thus indicating that the marker and the radioactive fat pass the gastrointestinal tract at the same rate under these experimental conditions. These results show that 75Se-triether possesses several of the properties of an ideal marker for fat absorption studies. Its advantages over other proposed markers for fat absorption studies are discussed. Simultaneous administration of 131L-TRIOLEIN AND 75Se-triether in a single dose may provide a reliable, rapid, and simple method to estimate intestinal fat absorption in man.

Evaluation of carbon-11 labelled phenylglycine and phenylalanine for pancreas scintigraphy.

Carbon-11 (t1/2 equals 20.4 min, beta-+) labelled DL-alpha-phenylalanine and DL-alpha-phenylglycine were administered intravenously to rats and the distribution of the radioactive amino acids over pancreas, liver, spleen, kidneys and blood was measured after several time intervals. From these results the ratios of the concentration in pancreas and liver were calculated and compared with the corresponding ratios from the literature for some 18-F-labelled aromatic amino acids and L-selenomethionine-75-Se. On the basis of this study it appears that DL-alpha-phenylglycine-1-11-C, in spite of a small percentage of the administered dose reaching the pancreas, and DL-alpha-phenylalanine-1-11-C are better suited to pancreas scintigraphy than L-selenomethionine-75-Se.