Tissue Distribution Studies In Mice Research Articles

Chromium-cage complex as contrast agent in MR imaging—Biodistribution studies of the [ 57Co]cobalt analogue

The synthesis and T 1 and T 2 relaxivities of the Cr(III)-(NH 2)-Sar-cage complex is reported. An outer-sphere relaxation mechanism is postulated for the relaxivity of the complex. Tissue distribution studies in mice using a [ 57Co]cobalt analogue as a radioactive tracer showed that the complex is excreted rapidly in the urine. Some renal uptake of the complex is seen. Appreciable uptake of labelled cage complex was observed in 3-methylcholanthrene induced murine rhabdomyosarcoma.

Synthesis of 6 beta-[131I](2'-iodo)ethyl-19-norcholest-5(10)-en-3 beta-ol and its tissue distribution in mice.

Iodine-131 labeled 6β- (2'-iodo) ethyl-19-norcholest-5 (10) -en-3β-ol has been prepared by iso-topic exchange using the hydrothermal melt method. A tissue distribution study in mice showed a rather selective localization of radioactivity in the adrenal gland, but the adrenal-to-liver concentration ratios were much lower than those previously observed with the iodine-131 labeled 6β-iodomethyl analog.

Disposition of intact liposomes of different compositions and of liposomal degradation products

Small unilamellar liposomes containing bovine serum albumin were prepared by a new double-emulsion technique and administered to mice and rats in intravenous injections. The elimination of intact liposomes, the association of phospholipid marker with lipoproteins, and the appearance of released internal marker and its degradation products were followed by column chromatography of plasma samples. In vitro labelled lipoproteins were administered to the animals in intravenous injections together with free bovine serum albumin and the elimination of the two substances was studied by closely related techniques. The clearance of intact PC : PS (4 : 1) liposomes from plasma was biphasic and much faster than that of labelled lipoproteins and bovine serum albumin either originating from liposomes or injected as such. The second elimination phase for these liposomes was barely detectable by our analytical methods. In contrast, DSPC : CHOL (2 : 1) liposomes showed a very significant second-phase elimination, with a half-life of 12 hr for the intact liposomes. In tissue distribution studies in mice, the major accumulation of liposomal markers was found in the liver and spleen, and less in the kidneys and intestinal wall. Uptake into liver and spleen appeared to be due to the uptake of intact liposomes, whereas the uptake into kidneys and gut wall was caused by the uptake of liposomal degradation products. The uptake of PC : PS (4 : 1) liposomes into the liver was higher than that of DSPC : CHOL (2 : 1) liposomes; the opposite was the case with their uptake into the spleen. In rats, too, liposomes of different compositions showed significant variations in stability and in plasma half-lives of intact liposomes. Generally, there was a considerable increase in the liposomal stability in the presence of cholesterol and when use was made of a phospholipid with a high transition temperature.

Iodine-125 labeled phenylphosphonic acid: A new radiopharmaceutical for long-term investigations of the skeleton

A skeletal seeking radiopharmaceutical labeled with a long-lived radionuclide was developed to evaluate regional bone formation and its subsequent resorption. The agent is [phosphonate (phenylmethylene hydroxy) bis] - I-125 or I-125 phi PA. Tissue distribution studies in mice (N = 16) showed approximately 40% of the administered dose to be retained by the skeleton up to 336 hours post IV injection. The percentage of the dose accumulated by the thyroid gland remained at less than 0.5%, indicating minimal deiodination of the I-125 phi PA. Whole body retention studies in the same species revealed a triexponential release pattern with the longest component comprising 33% of the dose with a biologic half-life of 962 days. A fractured rat tibia model was studied with I-125 phi PA and Tc-99m MDP. Chronic loss of the I125 phi PA relative to normal tibia was quantitated: five days (62.8%); 30 days (47.4%). Concomitant increased uptake of the Tc-99m MDP was observed at the fracture site relative to normal: five days (186%); 30 days (1,041%). The above data suggest that I-125 phi PA can be utilized to measure acute bone formation and chronic resorption.

Technetium-99m labelled imidodiphosphate: an improved bone-scanning radiopharmaceutical

Technetium-99m labelled imidodiphosphate was prepared in the presence of stannous ions. It was evaluated as a bone-scanning agent in animals and patients. Comparative tissue distribution studies in mice showed a relatively higher uptake of radioactivity in bone when 99Tcm -labelled pyrophosphate and diphosphonate. Accumulation of radioactivity in soft tissues, especially kidneys, was less with this radiopharmaceutical. Results in patients were most satisfactory in delineating skeletal bone and identifying bone lesions with relatively small tracer doses of the radiopharmaceutical.

Radiolabeled streptokinase and urokinase and their comparative biodistribution.

Abstract Streptokinase and urokinase were labeled with I-131 and Tc-99m. For iodination the chloramine-T method was used, and Tc-99m labelling was carried out in the presence of stannous ion. Thin layer chromatography and gel filtration showed a high labelling ratio, and autoradiography following immunoelectrophoresis showed the radioactivity over the bands corresponding to the enzymes. One hour tissue distribution study in mice showed the differences in the biological behavior of these radiopharmaceuticals. Clearance studies in dogs showed relatively faster clearance of urokinase with higher urinary excretion compared to streptokinase with minor differences between I-131 and Tc-99m labeled products.

Some Aspects of the Radiopharmaceutics of 99mTc-Phytate

This paper outlines the method of preparation of 99m-Tc-phytate and its use for scanning the reticuloendothelial system. The tissue distribution studies in mice and rats indicate that 99m-Tc-phytate is a safe and effective liver imaging agent. This was confirmed by preliminary studies in human subjects. The stability of the aqueous tin-phytate complex is remarkably good, and it could be successfully used for more than two months to prepare the labelled product.

Technetium-99m labelled pyrophosphate: a simple and reproducible bone scanning agent.

A simple method for the preparation of 99Tcm-pyrophosphate has been developed. A 1 per cent solution of sodium pyrophosphate in isotonic saline was added to a 1 per cent solution of stannous chloride in 1/3 N HCl in 10:1 ratio, pH automatically adjusted to 5. An adequate amount of 99TcmO4− eluate was added to 1 ml. of this mixture for bone scanning. Tissue distribution studies in mice showed rapid accumulation of the radiopharmaceutical in the bone. A higher value of the two-hour ratio of femur to liver specific activity was found suitable for the comparative evaluation of pyrophosphate preparations. Over 90 per cent of the radioactivity cleared from the blood in 30 minutes in dogs, and the urinary excretion was about 40 per cent in two hours. Serial scans in dogs showed an optimal visualization of the skeleton at about three hours. Good bone scans of adult patients were obtained in three to four hours using a tracer dose of the present radiopharmaceutical containing 5–10 mCi of 99Tcm along with 2–6 mg of pyrophosphate and 0·1–0·3 mg of tin.

Chromomycin A 3 , an antitumor antibiotic: tissue distribution studies in mice as measured by microbial assay.

A microbiological assay has been developed for chromomycin A(3), an antitumor antibiotic showing promise in human trials. The assay bacterium is a derived strain of Streptococcus faecalis resistant to methotrexate. Studies with mice revealed that relatively high concentrations of this antibiotic were maintained in the blood, kidneys, and liver of mice after a single-dose intraperitoneal injection of the drug.

Chromomycin A3, an Antitumor Antibiotic: Tissue Distribution Studies in Mice as Measured by Microbial Assay

A microbiological assay has been developed for chromomycin A(3), an antitumor antibiotic showing promise in human trials. The assay bacterium is a derived strain of Streptococcus faecalis resistant to methotrexate. Studies with mice revealed that relatively high concentrations of this antibiotic were maintained in the blood, kidneys, and liver of mice after a single-dose intraperitoneal injection of the drug.

Pseudourea, 2,2'-(9,10-anthrylenedimethylene) bis-(2-thio-, dihydrochloride) dihydrate: microbiological assay and tissue distribution studies in mice.

A microbiological assay for pseudourea, 2,2'-(9,10-anthrylenedimethylene)bis-(2-thio-, dihydrochloride) dihydrate (NSC 56054), a new anticancer agent, has been developed and tissue distribution studies in mice have been performed.

Pseudourea, 2,2′-(9,10-Anthrylenedimethylene) bis-(2-thio-, dihydrochloride) Dihydrate: Microbiological Assay and Tissue Distribution Studies in Mice1

A microbiological assay for pseudourea, 2,2'-(9,10-anthrylenedimethylene)bis-(2-thio-, dihydrochloride) dihydrate (NSC 56054), a new anticancer agent, has been developed and tissue distribution studies in mice have been performed.