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J S Fowler

Publications and source records attributed to J S Fowler.

At least 235 records · Page 13Linked to original sources
PubMed1984

Mapping brain neuroleptic receptors in the live baboon.

An experimental strategy for external detection of specific neuroleptic receptors in living brain using positron emission transaxial tomography (PETT) and [11C]spiroperidol was applied to the mapping of brain neuroleptic receptors in the live baboon. A double injection of [11C]spiroperidol with an intervening time interval for carbon-11 decay and an intervening dose of (+)-butaclamol to block specific neuroleptic receptors produced two sets of PETT scans which were subtracted to produce a three-dimensional map of relative regional binding of neuroleptic receptors in the baboon brain. Sixty-five percent of the total radioactivity in the striatum was bound to neuroleptic receptors at 65 min after injection.

Animals↗
PubMed1983

High-resolution circular ring positron tomograph with dichotomic sampling: Dichotom-I.

The circular ring transaxial positron camera developed earlier was refitted with a new dichotomic sampling scheme and aperture collimators on the detector array to improve the sampling and the overall system resolution. The z-axis slice thickness collimators were also limited to 1 cm, which corresponds to a slice thickness of 0.5 cm FWHM. Two different types of aperture collimators were adopted for high resolution (HR) and very high resolution (VHR) imaging, respectively. In HR mode a resolution of 6.5 mm FWHM was obtained without appreciable degradation of overall sensitivity, which represents a threefold improvement in resolution over the original system. In phantom studies with HR mode a sensitivity of 4500 counts s-1 muCi-1 cm-3 was obtained for a 20 cm diameter uniform phantom filled with water. A VHR mode experiment was also conducted to observe the ultimate resolution capability of the Dichotom-I system, and a resolution of 4.2 mm FWHM was obtained at the expense of sensitivity which was reduced by a factor of four from the HR mode experiment. The experience gained with Dichotom-I suggests a relatively simple and inexpensive modification of the existing NaI(T1) ring positron cameras, most of which suffer from low resolution due to poor sampling and poor intrinsic detector resolution.

Animals↗
PubMed1983

Specific binding of [11C]spiroperidol in rat brain in vivo.

Spiroperidol labeled with carbon-11, a short-lived positron-emitting radionuclide, was used to determine the time course of specific binding of this radioligand to the neuroleptic receptor in vivo in the rat. The three major bran pools--specifically bound, nonspecifically bound, and free (unbound)--were determined over a 60-mm time course by a rapid filtration technique, utilizing (-)- and (+)-butaclamol pretreatments to assess total and nonspecifically bound activities, respectively, in striatum and cerebellum. The ratio of specifically to nonspecifically bound pools in the striatum was 4.1 at 30 min and 5.1 at 60 min. Thus [11C]spiroperidol may be useful for labeling neuroleptic receptors in vivo for serial studies using positron emission transaxial tomography.

Animals↗
PubMed1983

Methodological aspects of acute toxicity testing particularly LD50 determinations present use in development of new drugs.

It is essential to have an adequate understanding of the acute toxic effects of a new drug. It may not be necessary however to blindly follow the full classical median lethal assay on every occasion. The LD50 was developed to obtain the maximum accuracy from a modest experimental size. The objective of the study and the limitations of the assay should not be overlooked however and undue precision should not be sought. Methodological aspects including species and maximum and minimum doses will be discussed. Other methods and approaches to acute toxicity will be recommended with a more broad approach to acute toxicity than lethality alone.

Animal Husbandry↗
PubMed1983

Quantitative autoradiography with radiopharmaceuticals, Part 2: Applications in radiopharmaceutical research: concise communication.

We describe the application of macroautoradiography, a relatively simple, quantifiable method for the evaluation of positron-emitting and gamma-emitting radiopharmaceuticals. We have investigated the response properties of two types of film to positron (F-18) and negatron (C-14) emitters. Variations in the response of film to increasing film-to-source distance are described, along with the effects of different intensifying screens and mounting tape. Digitization of whole-body autoradiograms (WBARG) in small animals was performed by using a videodensitometry system (videocamera interfaced to a computer). Quantitation was derived from analysis of a series of step-wedge standards that covered the range of radioactivities in the sample. By using a close-up lens on the videocamera, a 2- by 2-cm field is digitized as a 128 X 128 array, each pixel representing 156 X 156 micron. The effect of chlorpromazine (CPZ) on glucose metabolism in mice was studied by giving C-14 2DG followed by CPZ and F-18 FDG in the same animal. Muscle activity decreased and brown-fat activity increased. The high spatial resolution of this technique enables quantification in structures as small as the basal ganglia in mice. The use of dual-nuclide ARG permits each animal to be its own control, which greatly increases the utility of this method.

Animals↗
PubMed1982

18F-5-Fluorouridine, a new probe for measuring the proliferation of tissue in vivo.

(1) Increased metabolic trapping of labeled fluorouridine reflects the interaction of three parameters in rapidly proliferating tissues: increased rates of intracellular phosphorylation, increased rates of transport, and increased rates of synthesis of RNA. (2) We have taken advantage of these metabolic phenomena, demonstrating in this paper that the uptake of 18F-5-fluorouridine, a positron-emitting radiopharmaceutical, can provide a very practical means for measuring changes in proliferative states of tissues in vivo. (3) Two major changes in proliferative states have been examined: one involves changes in growth of normal mouse tissues induced by pharmacological agents; the other involves tumor growth and neoplastic infiltration in mice and rabbits. (4) We describe tracer experiments with 18F-5-fluorouridylate, prepared by enzymatic means, and with 18F-5-fluorouridine, prepared by both enzymatic means and direct radiochemical procedures. (5) Uptakes of 18F after a pulse of 18F-5-fluorouridine were increased in mouse spleen following phenylhydrazine treatment to induce increased splenic erythropoiesis. (6) Uptakes of 18F in various mouse tissues were decreased following pretreatment with actinomycin D. This finding is consistent with the known inhibitory action of actinomycin on RNA synthesis. (7) Intracerebral Zimmerman ependymoblastoma tumors showed extraordinarily high uptakes of fluorine-18 in mice injected intravenously with 18F-5-fluorouridylate or with 18F-5-fluorouridine in contrast to very low uptakes by normal brain tissue. (8) After intracerebral injection of mice with suspensions of L1210 leukemia cells, distant organs such as lung, liver, and spleen became involved. These tissues showed significant increases of radioactivity after pulse labeling with 18F-5-fluorouridylate consistent with histological evidence for infiltration of these tissues by neoplastic cells. (9) Intramuscular VX2 carcinoma tumors in rabbits showed localized uptakes of 18F significantly higher than surrounding normal muscle tissue. (10) The most important clinical implication of the present work is the promise that 18F-5-fluorouridine uptakes can be followed in humans by positron emission tomography. This would provide a direct means of measuring different rates of in vivo proliferation in neoplasms, hematologic tissues and other organs undergoing rapid growth changes.

Animals↗
PubMed1982

Haematological, coagulation and blood chemistry data in red-bellied tamarins Saguinus labiatus.

Haematology, coagulation and clinical chemistry data are reported for a group of male and female red-bellied tamarins (Saguinus labiatus). The tamarins were juvenile and young adults and were bred in captivity. High mean values for activities of alkaline phosphatase, alanine amino-transferase, aspartate aminotransferase and creatine kinase were noted. The findings are compared with data obtained from other members of the family Callitrichidae.

Animals↗
PubMed1982

Increased accumulation of 2-deoxy-2-[18F]Fluoro-D-glucose in liver metastases from colon carcinoma.

Three patients with liver metastases from colon carcinoma were studied with 2-deoxy-2-[F-18]fluoro-d-glucose (F-18-FDG) using positron emission tomography. The radioactivity in the metastatic tumor increased continuously following the injection of F-18-FDG, whereas it decreased in normal liver tissue. This resulted in the tumor to normal-liver ratio of 3.3-4.7 at 50 min after injection. The liver tumor was visualized as an increased accumulation of radioactivity in all patients, with the central area of the tumor showing less activity. These preliminary results suggest that F-18-FDG may be useful as a positive imaging agent for the detection and characterization of liver tumors.

Adenocarcinoma↗
PubMed1981

A shielded synthesis system for production of 2-deoxy-2-[18F]fluoro-D-glucose.

A remotely operated, shielded synthesis system for the production of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) for clinical studies has been developed. Using this system, 25 mCi of 18FDG are produced a the end of a 60-min synthesis from approximately 300 mCi of F-18 (total F-18 recovered from the target at the end of bombardment). The fractional distribution of F-18 among various components of the synthesis system has been measured. This yield of 18FDG (25 mCi) is ample for two consecutive human studies in house or for shipment to collaborating institutions within a 3-hr (door to door) radius.

Deoxy Sugars↗