Tissue Levels Of Radioactivity Research Articles

Tritiated Naltrexone Binding in Plasma from Several Species and Tissue Distribution in Mice

The binding of 15,16‐3H‐naltrexone in human, monkey, dog, guinea pig, rat, and mouse plasma was investigated over a range of concentrations, including predicted therapeutic levels. Studies using equilibrium dialysis at 37° indicate that the extent of binding is independent of naltrexone concentration over the concentration range of 1–500 ng/ml for dog plasma and of 0.1–500 ng/ml for human, monkey, guinea pig, rat, and mouse plasma. The extent of naltrexone binding in plasma is similar in the six species studied, the range being from 20% bound in rat plasma to 26% in plasma from beagle and mongrel dogs. This relatively low extent of naltrexone binding in plasma is consistent with previous findings of a large apparent volume of distribution for this drug in the dog. To investigate further the distribution of tritiated naltrexone, the tissue levels of radioactivity in mice at 1, 5, and 15 min after intravenous administration of 8‐3H‐naltrexone were determined. Naltrexone was rapidly distributed from plasma to tissues, with less than 4% of the dose being present in plasma at 1 min after injection.

Metabolic fate of cephacetrile after parenteral administration in rats and rabbits.

1. The metabolic fate of 14C-cephacetrile was studied in rats and rabbits. The plasma level of intravenously injected cephacetrile decreased with half-lives of 17 and 22 minutes in rats and rabbits respectively, this decline being associated with a rapid appearance of the active metabolite, desacetylcephacetrile. Intramuscularly injected cephacetrile was rapidly absorbed by rats with a maximum plasma level at 20 minutes and a half-life of 16 minutes. Cephacetrile and desacetylcephacetrile did not enter erythrocytes. Cephacetrile was weakly bound to the plasma protein in the rat, rabbit and man. 2. Both in rats and rabbits, almost all of the injected radioactivity was excreted in the urine within 72 hours as the intact antibiotic and desacetylcephacetrile, only small amounts appearing in feces via bile. Neither the gamma-lactone of desacetyl-7-cyanacetamidocephalosporanic acid nor the violet-reddish pigment (CGP-695) produced from cephacetrile were detectable in the plasma or urine of the animals. 3. In rats given the labeled antibiotic intravenously, the radioactivity was widely distributed with concentrations being high in the kidney, plasma and liver, and lowest in the brain. The radioactivity crossed the rat placenta and appeared in the fetus. Radioactivity in these tissues disappeared as the plasma level declined. 4. During daily intramuscular injection of 14C-cephacetrile to rat, no significant changes were observed in the peak level of the plasma radioactivity or in the half-lives. In addition, dosing of the labeled antibiotic for 7 days caused no increase in tissue levels of radioactivity.

The selective uptake of tamoxifen by human uterine tissue.

SummaryA series of patients who were suffering from dysfunctional uterine bleeding (menorrhagia) were dosed with [14C] tamoxifen prior to hysterectomy being performed. The proportion of the labelled dose which became bound to the various tissues of the uterus at different stages of the menstrual cycle was investigated. There was no apparent variation in the uptake of the compound during the menstrual cycle. However, it was found that the levels of radioactivity in the uterine tissues examined were higher than those found in the serum and that the proportion of radioactivity representing unchanged drug was two to three times that found in the serum. It appeared that tamoxifen had a definite affinity for the endometrium and that there was also some selective uptake by the corpus luteum.

Phenobarbital metabolism in ethanol-intoxicated rats.

The effects of an acute dose of ethanol on the metabolism of 14C-phenobarbital was studied in the rat. The ethanol-treated rats had higher blood and tissue levels of radioactivity than control animals for 10–12 h following oral administration of the drugs. No redistribution of radioactivity between blood and tissues was observed. Only unchanged phenobarbital was found in the brain, and only traces of phenobarbital metabolites were detected in the blood and liver. Ethanol inhibited the excretion of radioactivity during the first 12 h after dosing. This was due to reduced excretion of p-hydroxyphenobarbital. It is concluded that ethanol inhibits the hydroxylation of phenobarbital in the rat.

The study on metabolic fate of 5-fluorouracil-6-14C after percutaneous administration

The metabolic fate of 5-fluorouracil was studied in the rat by using 14C-labeled compound in ointment. Following the percutaneous administration of 5-fluorouracil in ointment, the rat excreted about 4% of the administered radioactivity in urine, 0.2% in feces, and 2.7% in respiratory CO2 within 72 hr, and about 90% of administered radioactivity remained at the site of application. Absorption of 5-fluorouracil in ointment from the skin was almost completed within the first 1 hr after ointment application and the maximum levels of radioactivity in rat tissues and blood also reached in about 1 hr after the application. Distribution of radioactivity in rat tissues was more highly located in the liver, kidneys, and in dermic and hypodermic tissues than in other tissues. After application of 0.5g per rat, of ointment containing radioactive 5-fluorouracil, the radioactive substances excreted in urine after 72 hr were unchanged 5-fluorouracil, α-fluoro-β-ureidopropionic acid, α-fluoro-β-guanidopropionic acid, and α-fluoro-β-alanine which were present in about 7.9%, 13.5%, 5.8%, 66.1%, and 3.7% of total radioactivity in the urine, respectively.

The whole body autoradiographic studies on the distribution of radioisotopes. XXIV. The absorption, distribution, and excretion of 3H-pregnanediol

Absorption, distribution, and excretion of 3H-pregnanediol after its percutaneous or intraperitoneal administration in female mice and rats were studied by autoradiography and liquid scintillation counting. Examination of absorption showed that 14% of the percutaneously administered radioactivity was absorbed during 48 hours. Microautoradiograms of rat skin applied with 3H-pregnanediol ointment suggested that the drug was absorbed through stratum malpighi of the cuticle and hair-follicles. Thirty minutes after intraperitoneal injection of 3H-pregnanediol in female mice, high concentration of the radioactivity was found in the gall bladder and intestinal content. A moderate level of the radioactivity was observed in the liver. Levels of radioactivity in other tissues were as low as that in blood. The lowest concentration was found in the brain. Twenty-four hours after intraperitoneal administration radioactivity in various organs except in intestinal contents decreased markedly.

Effect of feeding cod liver oil on the fate of radiotocopherol in sheep.

The metabolism of a single dose of 3H-DL-α-tocopherol was studied in 16 sheep fed a dystrophy-producing hay alone or supplemented with cod liver oil. During the experimental period, which lasted for 5 days after the radioisotope dosing, radioactivity was higher in the rumen liquor of cod liver oil fed sheep than in those which received only hay. Significantly lower levels of radioactivity were found in the non-saponifiable material of various tissues of cod liver oil fed sheep than in the corresponding tissues of the unsupplemented animals. By means of column chromatography, thin layer chromatography, and radioautography the bulk of liver radioactivity was identified as unchanged α-tocopherol. Possible reasons for the difference in tissue radioactivity levels between cod liver oil fed and unsupplemented sheep are discussed.

The distribution of cinnarizine and its metabolites in the rat

The study was conducted on 120 male Wistar rats and the radioactivity levels in the blood, liver, kidneys, heart, spleen, lungs, gonads, brain, urine and faeces were found at 7 time intervals ( 1 2 , 1, 2, 4, 8, 16, 32 hr) after administration of 14C-cinnarizine at 4 dosage rates (0.063, 2.5, and 40 mg/kg). The percentage of the tissue radioactivity due to the nonmetabolized drug was found for the blood, liver and brain. There was rapid resorption of the administered compound from the gastro-intestinal tract and peak tissue radioactivity levels were reached within 1 hr, except for the gonads in which the peak was reached only after 4–8 hr. Extensive metabolism occurred within 1 2 hr of treatment, and after 32 hr the tissue drug levels were negligible.

LEVELS OF RADIOACTIVITY IN TISSUES AND IN EXPIRED CARBON DIOXIDE AFTER ADMINISTRATION OF 1-C14-LABELLED PALMITIC ACID, 2-C14-LABELLED ERUCIC ACID, OR 2-C14-LABELLED NERVONIC ACID TO RATS

Palmitic acid -1-C14, erucic acid -2-C14, and nervonic acid -2-C14were administered to young adult rats by mouth, and levels of radioactivity in various body tissues and in respiratory CO2were determined. After [Formula: see text] hours about 20% of the label from palmitic acid and erucic acid and 30% from nervonic acid was still in the intestinal tract but after 24 hours less than 5% remained. At [Formula: see text] or 24 hours, tissue lipids of rats given palmitic acid generally contained a higher percentage of radioactivity administered than lipids from corresponding tissues of rats given erucic acid or nervonic acid. Very little radioactivity was found in brain lipids of either adult or 12-day-old rats given the labelled acids. The fatty acids were also given to adult rats by tail-vein injection and highest activities were again observed in tissue lipids of rats given palmitic acid.When given by mouth, palmitic acid contributed more radioactivity to respiratory CO2during the first 6 hours than erucic acid or nervonic acid, and peak activities did not occur until 2 to 3 hours after administration. When given by tail vein, erucic acid and nervonic acid contributed more activity to respiratory CO2than palmitic acid. Highest activities were observed during the first hour but the peak was reached somewhat later in rats given erucic acid or nervonic acid.

LEVELS OF RADIOACTIVITY IN TISSUES AND IN EXPIRED CARBON DIOXIDE AFTER ADMINISTRATION OF 1-C14-LABELLED PALMITIC ACID, 2-C14-LABELLED ERUCIC ACID, OR 2-C14-LABELLED NERVONIC ACID TO RATS

Palmitic acid -1-C14, erucic acid -2-C14, and nervonic acid -2-C14were administered to young adult rats by mouth, and levels of radioactivity in various body tissues and in respiratory CO2were determined. After [Formula: see text] hours about 20% of the label from palmitic acid and erucic acid and 30% from nervonic acid was still in the intestinal tract but after 24 hours less than 5% remained. At [Formula: see text] or 24 hours, tissue lipids of rats given palmitic acid generally contained a higher percentage of radioactivity administered than lipids from corresponding tissues of rats given erucic acid or nervonic acid. Very little radioactivity was found in brain lipids of either adult or 12-day-old rats given the labelled acids. The fatty acids were also given to adult rats by tail-vein injection and highest activities were again observed in tissue lipids of rats given palmitic acid.When given by mouth, palmitic acid contributed more radioactivity to respiratory CO2during the first 6 hours than erucic acid or nervonic acid, and peak activities did not occur until 2 to 3 hours after administration. When given by tail vein, erucic acid and nervonic acid contributed more activity to respiratory CO2than palmitic acid. Highest activities were observed during the first hour but the peak was reached somewhat later in rats given erucic acid or nervonic acid.

Specificity of zinc pathway in the rabbit: zinc-cadmium exchange

Marked perturbations of Zn65 clearance curves and subsequent blood and tissue radioactivity levels were produced in rabbits by the injection of either ZnSO4 or of CdSO4 carriers. The responses to challenge with cadmium loading, although not identical, were sufficiently similar to those obtained with zinc to suggest that cadmium may be an antimetabolite for zinc. In contrast, no deviations from control experiments were produced by injections of CuSO4, Ga(C2H3O2)2, or HgCl2. Hence, those segments of the physiological pathway of zinc through the body that were tested by these experiments proved to have sufficient specificity to discriminate completely against these latter elements.

Uptake and excretion of radioactive rose bengal dye in normal dogs.

SummaryIn normal adult mongrel dogs, radioactive rose bengal dye is rapidly removed from the blood stream with radioactivity reduced 50% in 5 to 10 minutes following intravenous injection of the dye. The liver takes up the dye rapidly, starting within 4 minutes, and excretes it quickly, as evidenced by appearance of dye in the bile 6 minutes after administration. Approximately 20% of the tagged dye passed through the bile in one hour. Urinary excretion is almost negligible, with approximately 0.1% of total dye present in the urine in 60 minutes. Renal, splenic, and pancreatic tissue levels of radioactivity are insignificant and probably represent amount of dye in the blood stream. Radioactivity over the duodenum is evident within the first hour and probably represents amount of dye excreted into the bile.

The effect of vitamin B 6 on the in vivo utilization of radioactive phenylalanine

The in vivo incorporation of phenylalanine-C 14 into tissues of control and vitamin B 6-deficient rats was investigated. Thirty minutes after the administration of the isotope, markedly higher levels of C 14 were found in the acid-soluble, lipide, and protein fractions of all control tissues examined as compared to those of vitamin B 6-deficient rats. Two hours and 7 hr. after the administration of phenylalanine-C 14, the acid-soluble fraction of all tissues from vitamin B 6-deficient animals exhibited higher levels of radioactivity than did similar tissues from control animals; however, the radiocarbon concentration in the lipides and proteins of control tissues remained higher. The administration of 1 mg. of pyridoxal daily for 3 days prior to the injection of phenylalanine-C 14 affected only slightly the uptake of C 14 in control animals; the levels of radioactivity in tissues from deficient animals similarly treated with pyridoxine tended to approximate control levels. The relation of these findings to amino acid transport into cells and to protein metabolism is discussed.