Analysis of the radiorespirometric pattern after administration of [U-14C] glucose to Ehrlich ascites tumor-bearing mice

Ehrlich ascites tumor-bearing mice were subjected to ¹⁴CO₂ radiorespirometric analysis after administration of [U-¹⁴C]glucose, and the results were compared with the levels of host liver glycolytic enzyme activities and the uptake of the radioactivity into the liver. After IP administration of [U-¹⁴C]glucose, there was a progressive decline in respiratory ¹⁴CO₂ after the transplantation of the Ehrlich ascites tumor cells. The peak time (PT) was about 10 min on day 1, but thereafter was increasingly delayed, and could not be determined on day 13. Peak height (PH) and yield value (YV) were both considerably decreased, and again the magnitudes of the changes increased with the time after transplantation of the tumor cells. Glycolytic enzyme activities in the host liver were at normal levels 13 days after transplantation of the tumor cells. The uptake of the radioactivity into the liver after IP administration of [U-¹⁴C]glucose began to decline from day 5 and was 50% the value in normal mice 13 days after transplantation of the tumor cells. These results indicate that the radiorespirometric patterns with [U-¹⁴C]glucose reflects hepatic biochemical changes rather well.     

Kinetic differences and similarities among 3 tracers of myocardial glucose uptake.

Two glucose tracer analogs, uniformly labeled [14C]2-deoxyglucose ([U-14C]2DG) and FDG, are widely used to assess myocardial glucose uptake. Despite the similar electron configuration of the fluorine and hydrogen atoms, uptake of the 2 tracer analogs may not be the same because of their different electronegativity. METHODS: To test this hypothesis, we determined glucose uptake in isolated rat hearts simultaneously from the accumulation of [U-14C]2DG radioactivity in the tissue, by continuous monitoring of FDG accumulation with a pair of coincidence detectors and by cumulative release of 3HOH from [2-3H]glucose. A first group of hearts was perfused at physiologic workload with Krebs-Henseleit buffer containing 10 mmol/L glucose; a second group, with the buffer containing 5 mmol/L glucose plus 0.4 mmol/L oleate and 1 mU/mL insulin. Third and fourth groups were subjected to ischemia (i.e., a 75% reduction in coronary flow) and reperfused. For the third group, the buffer contained 5 mmol/L glucose; for the fourth, 5 mmol/L glucose plus 0.4 mmol/L oleate. RESULTS: No difference in the total amount of tracer accumulation in any group was seen between the 2 tracer analogs. The ratio [+/-SD] of [U-14C]2DG to FDG ranged from 0.93+/-0.09 to 1.31+/-0.11. However, both tracer analogs paralleled glucose uptake in the absence of insulin but underestimated glucose uptake significantly in the presence of insulin. Changes in 2DG uptake with ischemia and reperfusion could be detected only with FDG. CONCLUSION: Although uptake of [U-14C]2DG equals uptake of FDG quantitatively, acute changes in 2DG uptake (and, thus, in the tracer-tracee relationship) are detectable only with the fluorine-labeled tracer.     

Radiorespirometric study of glucose metabolism in liver-damaged rats

Changes in glucose metabolism in rats during feeding with 3-methyl-4-(dimethylamino)azobenzene(3-Me-DAB) were investigated by radiorespirometry with ¹⁴C-labelled carbohydrates as substrates, in relation to the levels of liver glycolytic enzyme activities.Rats were fed on 0.06% 3-Me-DAB for 7 weeks. Radiorespirometry was carried out by the IP administration of [U-¹⁴C]glucose 2.5 Ci or [1-¹⁴C]acetate 2.0 Ci weekly during the experimental period.In the analysis of the radiorespirometric pattern obtained with [U-¹⁴C]glucose, the peak time (PT) was markedly shortened at week 4. At week 6 of 3-Me-DAB feeding, the peak height (PH) and yield value (YV) both increased significantly with concomitant shortening of PT. The duration of the activation in radiorespirometric parameters was paralleled reasonably well by that of glycolytic enzyme activity; the activation of liver glucose-6-phosphate dehydrogenase (G-6-PDH) shortens PT, while the activation of the tricarboxylic acid (TCA) cycle increases YV.This study showed that the radiorespirometric pattern reflected glucose metabolism in the liver well. In conclusion, radiorespirometric analysis with ¹⁴C-labelled glucose as a substrate may be useful for the clinical diagnosis of liver diseases.     

C-11-labeled glucose and its utilization in positron-emission tomography

Carbon-11-labeled glucose was prepared photosynthetically using the green alga Scenedesmus obtusiusculus Chod. The carbohydrates were extracted from the cells with dilute HCI and the glucose was isolated and purified using high-performance liquid chromatography. The manipulations in the hot cell are described. Analysis of the material (gas liquid chromatography and HPLC) showed that the glucose obtained was radiochemically pure. The total incorporation of the 11CO2 added to the algae was 60-80%. The radiochemical yield of pure carrier-added glucose was approximately 25%, at 40 min after E.O.B. including the HPLC purification and sterile filtration. The C-11 glucose uptake in rat brain was compared with that of commercial D[U-14C]glucose, and preliminary PET studies with D-[11C]glucose in a patient with a brain infarct are presented.     

Enzymatic syntheses of carbamyl phosphate, L-citrulline, and N-carbamyl L-aspartate labeled with either 13N or 11C

[13N]- and [11C]carbamyl phosphate, L-[omega-13N]citrulline, L-[ureido-11C]citrulline, [carbamyl-13N]- and [carbamyl-11C]carbamyl-L-aspartate were synthesized using carbamyl phosphate synthetase co-immobilized with either aspartate transcarbamylase or ornithine transcarbamylase. Carbamyl L-[13N]aspartate was enzymatically prepared from carbamyl phosphate and L-[13N]aspartate. The tissue distribution of radioactivity in mice after injection of radiolabeled ammonia, carbamyl phosphate or citrulline was studied. The tissue distribution of isotope derived from [13N]carbamyl phosphate and [13N]ammonia were similar, with the exception of liver, brain and pancreas, in which 13NH3 uptake was higher after retroorbital injection. The distribution of label derived from L-[omega-13N]- and L-[ureido-11C]citrulline was similar. Substantial tumor (Sarcoma-180) uptake of label from L-citrulline was observed.     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

Tumor uptake of radiolabelled pyrimidine bases and pyrimidine nucleosides in animal models: VII. [2-14C]-5-ethyl-1-(2'-deoxy-beta-D-ribofuranosyl)uracil

The differential tissue uptake and blood clearance of [2-14C]-5-ethyl-1-(2'-deoxy-beta-D-ribofuranosyl)uracil [2-14C]-5-EtUdR) in BDF1 mice bearing Lewis Lung carcinomas has been investigated. The kidney, gall bladder with contents and GIT exhibited the greatest concentration of radioactivity relative to the tumor up to 30 min after i.v. injection of [2-14C]-5-EtUdR. Blood, spleen, liver and muscle exhibited a lower concentration of radioactivity than the former group. Radioactivity levels in the stomach and skin were similar to that of the tumor. The long bone had the lowest radioactivity level of all the tissues examined. During the 1-3 h period following injection, the tumor contained more radioactivity than most other tissues with the exception of the gall bladder and contents, GIT and kidney. Packed erythrocytes contained 62-78% of the radioactivity in the whole blood. Clearance of injected radioactivity from whole blood followed two-compartment kinetics. Elimination was mainly renal, although some biliary excretion of injected radioactivity was also observed.     

Oxidation of lactate in rats after short-term strenuous exercise

Oxidation of lactate and glucose was investigated in rats after short-term strenuous running to exhaustion at a speed of 80-110 m.min-1, lasting about 100 sec. Immediately after the exercise, 4 microCi of [U-14C]lactate (LA and AR) or 9.4 microCi of [U-14C]glucose (GL) was injected into the aorta through an indwelling catheter. In AR, the rats ran at a speed of 25 m.min-1 for 20 min after injection of [U-14C]lactate. Expired gas was collected by a bottomless metabolism chamber while the rats were on the treadmill for 120 min. Blood lactate concentration tended to decrease faster in AR than in LA. Peak evolution of 14CO2 expiration occurred at 12.5 min recovery in LA, 7.5 min of recovery in AR, and 35 min of recovery in GL. Cumulative percent recovery of 14C as 14CO2 was 48.5% +/- 2.8% in LA, 74.0% +/- 2.9% in AR, and 18.6% +/- 1.6% (mean +/- SE) in GL. Significant differences were found in these rates between groups (P less than 0.01). It was suggested that a great deal of lactate was oxidized directly, not after conversion to glucose in rats after short-term strenuous exercise to exhaustion and mild exercise following strenuous exercise (active recovery) enhanced lactate oxidation.     

Intracellular reactions affecting 2-amino-4-([11C]methylthio)butyric acid ([11C]methionine) response to carbon ion radiotherapy in C10 glioma cells

PurposeThe response of 2-amino-4-([¹⁴C]methylthio)butyric acid ([¹⁴C]Met) uptake and [¹²⁵I]3-iodo-alpha-methyl-l-tyrosine ([¹²⁵I]IMT) uptake to radiotherapy of C10 glioma cells was compared to elucidate the intracellular reactions that affect the response of 2-amino-4-([¹¹C]methylthio)butyric acid ([¹¹C]Met) uptake to radiotherapy.MethodsAfter irradiation of cultured (3 Gy) or xenografted C10 glioma cells (25 Gy) using a carbon ion beam, the accumulation of [¹⁴C]Met and [¹²⁵I]IMT in the tumors was investigated. The radiometabolites in xenografted tumors after radiotherapy were analyzed by size-exclusion HPLC.Results[¹⁴C]Met provided earlier responses to the carbon ion beam irradiation than [¹²⁵I]IMT in both cultured and xenografted tumors. While [¹²⁵I]IMT remained intact in xenografted tumor before and after irradiation, the radioactivity derived from [¹⁴C]Met was observed both in high molecular fractions and intact fractions, and the former decreased after irradiation.ConclusionThe earlier response of [¹¹C]Met uptake to tumor radiotherapy could be attributable to the decline in the intracellular energy-dependent reactions of tumors due to radiotherapy.     

Metabolic studies with L-[1-14C]tyrosine for the investigation of a kinetic model to measure protein synthesis rates with PET

To evaluate a kinetic model for measuring protein synthesis rates by positron emission tomography (PET) in neoplastic and normal tissue, metabolic studies with L-[1-14C]tyrosine were carried out. As an animal model, rats bearing Walker 256 carcinosarcoma were used. Within 60 min after injection, several metabolic parameters were measured. The highest radioactivity uptake, expressed as the differential absorption ratio, was found in pancreas, followed by liver, tumor, and brain. A rapid decarboxylation was observed during the first 15 min. After 60 min, 7.4% of the total injected 14C was expired as 14CO2. In plasma a significant amount of [14C]bicarbonate was detected, but in tissue the amount was negligible. Protein incorporation increased with time. The incorporation rate was the highest in the liver followed by pancreas, tumor, and brain tissues. At 60 min after injection, more than approximately 80% of the 14C in tissue was protein bound. In plasma after a rapid clearance during the first 15 min, the total 14C level increased rapidly and paralleled the increase of protein-bound 14C. As nonprotein [14C]metabolites, in plasma, tumor and brain tissues, p-hydroxyphenylpyruvic acid, p-hydroxyphenyllactic acid, and unidentified metabolites were observed by high performance liquid chromatography. The formation of 14C-labeled 3,4-dihydroxyphenylalanine was found to be negligible. The total amount of these nonprotein metabolites increased with time. At 60 min after injection the percentages of the total nonprotein metabolites and [14C]bicarbonate were only 5.0%, 1.9%, and 3.7% in plasma, tumor and brain tissue, respectively. From our data it is concluded that [11C]carboxylic-labeled tyrosine would be a suitable radiopharmaceutical for measuring protein synthesis rates in neoplastic and normal tissue by PET.     

Evaluation of 4'-[methyl-14C]thiothymidine for in vivo DNA synthesis imaging.

We evaluated 4'-[methyl-11C]thiothymidine ([methyl-11C]S-dThd) to obtain a thymidine analog that might prove simpler to use for imaging DNA synthesis and that might follow the same biochemistry as its surrogate. METHODS: [Methyl-14C]S-dThd was synthesized by rapid methylation of 5-trimethylstannyl-4'-thio-2'-deoxyuridine via a palladium-mediated Stille coupling reaction with 14C-methyl iodide. Degradation of [methyl-14C]S-dThd, when incubated in human blood, was analyzed by high-performance liquid chromatography (HPLC). The in vivo potential of [methyl-14C]S-dThd was evaluated by studying its distribution in EMT-6 mammary carcinoma-bearing mice. 2-Fluoro-2'-deoxycytidine, a potent inhibitor of DNA synthesis, was used to modulate cell proliferation. Tissue extraction was also performed to investigate the incorporation of [methyl-14C]S-dThd into DNA. RESULTS: [Methyl-14C]S-dThd was obtained in a 31%-41% radiochemical yield (calculated from 14C-methyl iodide) at 130 degrees C, 5-min reaction in N,N-dimethylformamide followed by semipreparative HPLC purification. The radiochemical purity of [methyl-14C]S-dThd was >99% and the specific activity was 2.04 GBq/mmol (according to the specific activity of 14C-methyl iodide). [2-14C]Thymidine, when incubated with human blood, demonstrated rapid degradation. In contrast, [methyl-14C]S-dThd was stable with <3% degradation at 60 min. An in vivo distribution study showed the accumulation of radioactivity in proliferating tissues (spleen, thymus, duodenum, and tumor). On the other hand, the radioactivity of nonproliferating tissues (lung, liver, kidney, and muscle) was rapidly cleared in parallel with the clearance of blood radioactivity. The tumor uptake of [methyl-14C]S-dThd was high (8.8 percentage injected dose per gram at 60 min) and selective (tumor-to-blood ratio, 12.2 at 60 min). 2-Fluoro-2'-deoxycytidine pretreatment significantly reduced the tumor uptake of [methyl-14C]S-dThd. Relative blood flow as measured by the uptake of 4-[N-methyl-14C]iodoantipyrine was similar between the treated and untreated groups. Tissue extraction studies showed that most of the total tissue radioactivity of rapidly proliferating tissues was recovered in the DNA fraction at 60 min after [methyl-14C]S-dThd injection. CONCLUSION: The labeling procedure is rapid and suitable for 11C labeling. Positron-labeled 4'-thiothymidine should be useful for imaging DNA synthesis by PET.     

Application of lectins to tumor imaging radiopharmaceuticals

We investigated the in vitro binding of 125I-lectins to Ehrlich ascites tumor (EAT) cells and in vivo uptake of 125I-lectins in Ehrlich solid tumor (EST) bearing mice. In in vitro binding assays, phaseolus vulgaris agglutinin (PHA), pisum sativum agglutinin(PSA), and concanavalia agglutinin(Con A) showed a high affinity for EAT cells. The in vivo biodistribution of 125I-lectins showed 125I-I-PSA to be significantly taken up into EST tissues 24 h postinjection. After IV injection of 125I-PSA, uptake of the radioactivity into the tumor tissues reached a maximum at 6 h, and thereafter decreased. Rapid clearance of the radioactivity from blood and its excretion into kidney soon after injection of 125I-PSA were observed. When compared with the biodistribution of 67Ga-citrate in EST bearing mice 24 h postinjection, tumor to liver (T/B), tumor to muscle (T/M), and tumor to blood (T/B) ratios were superior for 125I-PSA. At 6 h postinjection, the T/B-ratio of 125I-PSA was 2.5, and this value may be sufficient to enable discernible diagnostic images. Our results suggest that PSA might be a useful tumor imaging radiopharmaceutical.     

Preferential labeling of glial and meningial brain tumors with [2-(14)C]acetate.

Acetate is preferentially transported into and metabolized by astrocytes, rather than synaptosomes or neurons, and labeled acetate is used as a glial reporter molecule to assess glial metabolism and glial-neuronal interactions. Because monocarboxylic acid transporter specificity might confer a phenotype to help localize, detect, and characterize brain tumors of glial origin, use of [2-(14)C]acetate and [(14)C]deoxyglucose (a glucose analog metabolized by all brain cells) was compared in rat and human brain tumors. METHODS: Cultured C6 glioma or U-373 glioblastoma/astrocytoma tumor cells were injected into the caudate nucleus of anesthetized CDF Fisher rats; 2--3 wk later, an intravenous pulse of [2-(14)C]acetate or [(14)C]deoxyglucose was given, and timed blood samples were drawn during the 5- or 45-min experiment, respectively. Local (14)C levels in the brain were assayed by quantitative autoradiography, and acetate uptake or glucose use was calculated. Uptake and metabolism of the [(14)C]acetate was also assayed in C6 glioma and human surgical tumor samples in vitro. RESULTS: [(14)C]Acetate uptake into rat brain C6 tumors was 9.9 +/- 2.1 mL/100 g/min, compared with 3.9 +/- 1.0 mL/100 g/min in contralateral tissue (n = 6; P < 0.001), and was much higher than that into other brain structures (e.g., 5:1 for white matter and 2:1 for cortical gray matter). Glucose use in C6 tumors was 111 +/- 34 micromol/100 g/min, versus 81 +/- 5 micromol/100 g/min in contralateral tissue (n = 6; P = 0.08); no left-right differences in glucose use or acetate uptake were seen in other brain structures. The tumor-to-contralateral-tissue ratio for acetate (2.3 +/- 0.3) exceeded that for deoxyglucose (1.4 +/- 0.5) (P < 0.05), indicating that acetate is a sensitive C6 glioma marker. [(14)C]Acetate uptake also demarcated a few 3-wk-old C6 tumors that had unlabeled necrotic cores. U-373 tumors were smaller than C6 tumors in rat brain and were detected equally well with [(14)C]acetate and [(14)C]deoxyglucose. In vitro uptake of [(14)C]acetate into human glioblastoma or meningioma tumors was higher than uptake into pituitary adenoma. Rat C6 and human tumors with high uptake metabolized acetate to acidic compounds and amino acids. CONCLUSION: Tumor imaging with radiolabeled acetate can help to localize and classify brain tumors. Transporter and metabolic substrate specificity are traits that can be exploited further for in vivo imaging of brain glial tumors.     

A 13C NMR study of the application of [U-13C]succinate for metabolic investigations in rabbit renal proximal convoluted tubular cells

The fate of the 13C label arising from [U-13C]succinate in rabbit renal proximal convoluted tubular (PCT) cells, incubated with [U-13C]succinate, was investigated by 13C NMR spectroscopy of the perchloric acid extracts of the cell pellets. The 13C label of [U-13C]succinate was predominantly metabolized into glutamate, glutamine, and into glucose, lactate, and alanine, which is the consequence of a carbon efflux of the label from the Krebs cycle at the stage of alpha-ketoglutarate and oxaloacetate, respectively.     

131 I标记人源抗HBs Fab瘤内注射治疗荷人肝癌裸鼠的实验研究

目的　探讨13 1I标记人源抗乙肝表面抗原单克隆抗体Fab片段 (抗HBsFab)瘤内给药治疗荷人肝癌裸鼠移植瘤的合理性。方法　荷瘤裸鼠分为 5组 ,分别经瘤内注射13 1I 抗HBsFab、13 1I 无关Fab、13 1I、PBS及腹腔注射13 1I 抗HBsFab。 5d后每组各取 2只作组织分布测定 ,其余观察 3周 ,计算各组肿瘤生长抑制率。结果　瘤内注射13 1I 抗HBsFab组放射性计数瘤 /肝比值是腹腔注射组的 9倍 ,3周后前者肿瘤生长抑制率高于后者 ,分别为 62 .3%和 46.7%。结论　采用瘤内注射13 1I标记人源抗HBsFab导向治疗肝癌 ,具有低毒高效的治疗作用 ,临床实用价值大     

Characterization of acetate metabolism in tumor cells in relation to cell proliferation: acetate metabolism in tumor cells

To reveal the metabolic fate of acetate in neoplasms that may characterize the accumulation patterns of [1-(11)C]acetate in tumors depicted by positron emission tomography. Four tumor cell lines (LS174T, RPMI2650, A2780, and A375) and fibroblasts in growing and resting states were used. In uptake experiments, cells were incubated with[1-(14)C]acetate for 40 min. [(14)C]CO(2) was measured in the tight-air chamber, and the metabolites in cells were identified by thin layer chromatography and paper chromatography. The glucose metabolic rate of each cell line was measured with [2,6-(3)H]2-deoxy-glucose (DG), and the growth activity of each cell line was estimated by measuring the incorporation of [(3)H]methyl thymidine into DNA. Compared with resting fibroblasts, all four tumor cell lines showed higher accumulation of (14)C activity from [1-(14)C]acetate. These tumor-to-normal ratios of [1-(14)C]acetate were larger than those of DG. Tumor cells incorporated (14)C activity into the lipid-soluble fraction, mostly of phosphatidylcholine and neutral lipids, more prominently than did fibroblasts. The lipid-soluble fraction of (14)C accumulation in cells showed a positive correlation with growth activity, whereas the water-soluble and CO(2) fractions did not. These findings suggest that the high tumor-to-normal ratio of [1-(14)C]acetate is mainly due to the enhanced lipid synthesis, which reflects the high growth activity of neoplasms. This in vitro study suggests that [1-(11)C]acetate is appropriate for estimating the growth activity of tumor cells.     

Application of lectins to tumor imaging radiopharmaceuticals

We investigated the in vitro binding of ¹²⁵I-lectins to Ehrlich ascites tumor (EAT) cells and in vivo uptake of ¹²⁵I-lectins in Ehrlich solid tumor (EST) bearing mice. In in vitro binding assays, phaseolus vulgaris agglutinin (PHA), pisum sativum agglutinin (PSA), and concanavalia agglutinin (Con A) showed a high affinity for EAT cells. The in vivo biodistribution of ¹²⁵I-lectins showed ¹²⁵I-PSA to be significantly taken up into EST tissues 24 h postinjection. After IV injection of ¹²⁵I-PSA, uptake of the radioactivity into the tumor tissues reached a maximum at 6 h, and thereafter decreased. Rapid clearance of the radioactivity from blood and its exretion into kidney soon after injection of ¹²⁵I-PSA were observed. When compared with the biodistribution of ⁶⁷Ga-citrate in EST bearing mice 24 h postinjection, tumor to liver (T/B), tumor to muscle (T/M), and tumor to blood (T/B) ratios were superior for ¹²⁵I-PSA. At 6 h postinjection, the T/B-ratio of ¹²⁵I-PSA was 2.5, and this value may be sufficient to enable discernable diagnostic images. Our results suggest that PSA might be a useful tumor imaging radiopharmaceutical.     

Incorporation of blood lactate and glucose into tissues in rats after short-term strenuous exercise

The purpose of this study was to investigate the main site of removal of blood lactate and glucose and which is the more important substrate for muscle glycogen resynthesis in rats after short-term strenuous exercise, to exhaustion. Male Wistar rats ran to exhaustion at a speed of 70-100m.min-1. Immediately after the exercise the rats received an injection of [U-14C]lactate (LA, 0.025 microCi.g-1, n = 5) or [U-14C]glucose (GL, 0.015 microCi.g-1, n = 5) into the aorta through an indwelling catheter. The rats were sacrificed after 40 min of recovery. During 40 min of recovery, 20.4% +/- 2.0% (mean +/- SE) of 14C injected was recovered as 14CO2 in LA, while 4.1% +/- 0.4% of 14C was recovered as 14CO2 in GL. In LA, the content of 14C incorporated per tissue weight in the vastus lateralis was significantly greater than that in the kidney, heart, and blood, while in GL that in the vastus lateralis was significantly greater than in any other tissues measured. The incorporation of 14C-glucose into muscle glycogen (vastus lateralis) was about five times greater than that of 14C-lactate. Data from this study indicate that lactate and glucose are incorporated from the blood into the skeletal muscle which was active during exercise and that blood glucose is a more preferred substrate for muscle glycogen resynthesis in rats after strenuous exercise to exhaustion.     

Radioprotection of liver lipids of whole-body gamma-irradiated female rats by cystamine.

The effect of administration of cystamine (5 mg/100 g body weight) before 1200 R whole-body gamma irradiation has been studied on irradiation-induced changes in liver and its subcellular fractions'lipids of fasted female rats. Cystamine prevented the irradiation-induced increase in liver triglycerides and liver mitochondrial total phospholipids, but it decreased microsomal total phospholipids and proteins. Cystamine prevented the radiation-induced increased 32P-radioactivity (counts/min/mumole phospholipid phosphorus) of microsomal phosphatidyl choline. Cystamine prevented the radiation-induced increased uptake of NaH232PO4 (counts/min/g liver) in liver microsomal phosphatidyl ethanolamine and supernatant phosphatidyl choline; but in microsomal phosphatidyl choline, cystamine did not do so, but on the other hand it itself increased the uptake in control rats. Cystamine did not prevent the irradiation-induced decreased incorporation of (U-14C)glucose into liver triglycerides, total phospholipids and phosphatidyl choline. Cystamine itself decreased the incorporation of (U-14C)glucose into liver triglycerides and phosphoglycerides of control rats.     

The application of isotopes to the study of lactate metabolism

The use of 14C as tracer to measure lactate turnover and oxidation and its role in gluconeogenesis are discussed. Lactate is formed as well as utilized in many cells, and most of it in the body is present within cells so that interpretation of 14C data from labelled lactate is more complex and more difficult than that of compounds present largely extracellularly, such as glucose. Apparent uptake of [14C]lactate may occur in the absence of net lactate utilization, and 14CO2 production does not provide a measure of true lactate oxidation. In vivo sites of tracer administration and sampling of blood are of critical significance for evaluation of lactate turnover, lactate space, its incorporation into glucose, and oxidation.