PubMed Health⌕ Search

Biomedical subjects

R L Hayes

Publications and source records attributed to R L Hayes.

At least 181 records · Page 10Linked to original sources
PubMed1981

Studies of the in vivo entry of Ga-67 into normal and malignant tissue.

Previous studies of the effect of scandium on the tissue distribution of Ga-67 suggest that Ga-67 makes its initial in vivo entry into normal and malignant tissues by different routes. (Scandium blocking of plasma protein Ga-67 binding increased Ga-67 excretion, decreased its uptake in normal tissues, but had little effect on rodent tumors.) In further studies we have used other methods to alter the plasma binding of Ga-67. Iron saturation of plasma produced effects on Ga-67 tissue distribution similar to those observed with scandium. On the other hand, increasing Ga-67 plasma binding through induction of anemia and administration of apotransferrin produced the reverse of the effects observed with scandium and iron. We conclude that the initial in vivo entry of Ga-67 into tumor tissue involves mainly an unbound or loosely bound form of Ga-67, whereas its uptake by normal soft tissues is strongly promoted by its binding to transferrin.

Animals↗
PubMed1980

The effect of scandium on the tissue distribution of Ga-67 in normal and tumor-bearing rodents.

In rats and mice the intravenous administration of scandium before or with Ga-67 produces an increase in Ga-67 excretion and bone deposition, coupled with pronounced decreases in the uptake of Ga-67 in soft tissues. These effects result from the blocking by scandium of Ga-67 plasma-protein binding sites, which forces Ga-67 into an unbound or loosely bound state. This increases Ga-67 excretion and bone deposition, which in turn acts to produce greatly reduced Ga-67 uptake in soft tissues. When tumor-bearing rats and mice are administered scandium, similar effects occur, but the uptake of Ga-67 by tumor tissue remains unchanged. This suggests that Ga-67 enters tumor and normal soft tissues by different routes. With tumor, an unbound or loosely bound form of gallium is primarily involved, whereas with normal soft tissues this route is apparently of minor importance.

Animals↗
PubMed1979

1-aminocyclobutane[11C]carboxylic acid, a potential tumor-seeking agent.

1-Aminocyclobutane[14C]carboxylic acid [C-14) ACBC] was incorporated preferentially by several tumor types in rats and hamsters. The agent was cleared rapidly from rat blood, attaining its maximum tissue concentrations within 30 min after i.v. injection. Carrier ACBC had little effect on the tissue distribution of (C-14) ACBC. This agent showed no affinity for a Staphylococcus aureus abscess in rats. The total excretion was low, 3.6% in 2 hr. (C-11) ACBC was synthesized in amounts up to 415 mCi (55% chemical yield) using our modified Bücherer-Strecker technique. Forty minutes were required for the two-step synthesis and chromatographic purification. ACBC was found to be nontoxic in three animal species. The radiation dose from (C-11) ACBC should be minimal. (C-11) ACBC thus appears to have good potential as a tumor-seeking agent, particularly when used with a positron emission computed tomograph.

Adenocarcinoma↗
PubMed1979

Carbon-11-labeled amino acids for the rectilinear and positron tomographic imaging of the human pancreas.

Modification of the Bücherer-Strecker amino acid synthesis facilitated the production of DL-[11C]tryptophan and DL-[11C]valine for clinical trials in patients with proven or suspected pancreatic disease. Examples of rectilinear scans and tomographic images of the pancreas are presented in this initial paper. Positron computed tomography was done with the ORTEC ECAT system. Rapid localization of these C-11-labeled amino acids and fast clearance from the plasma permit almost immediate examination following i.v. injection. Illustrative images include the normal pancreas, pancreatitis, and pancreatic carcinoma. The use of positron tomobraphy with C-11-labeled DL-tryptophan and DL-valine appears to offer a new and promising diagnostic modality for the detection and study of pancreatic diseases.

Carbon Radioisotopes↗
PubMed1979

Effect of food intake on the tissue distribution of gallium-67: concise communication.

Fasting affects the body retention and tissue distribution of Ga-67 in experimental animals. In Ga-67 experiments, therefore, a difference in food intake between treated and control animals might result in confusing side effects. We have observed this in irradiation studies. It is suggested that a fasting regimen should be imposed in any Ga-67 animal study where an alteration in food intake might be experienced in the treated group.

Animals↗
PubMed1979

DL-[Carboxyl-11C]tryptophan, a potential agent for pancreatic imaging; production and preclinical investigations.

In animal studies, DL-[carboxyl-14C]tryptophan [DL-Try(C-14)] showed a high specificity for the pancreas, which suggested the potential of DL-[carboxyl-11C]tryptophan [DL-Try(C-11)] for clinical pancreatic inaging. The blood clearance and tissue uptake of the amino acid were very rapid, and no carrier effect was observed through a dose of 5 mg/kg. None of three transplanted hamster pancreatic adenocarcinomas that we studied showed a selective uptake of DL-Try(C-14) by the tumor, and none of the three enzymatic regimens investigated gave significant enhancement of the pancreatic specificity. Commercial L-Try(C-14) gave slightly better pancreatic specificity than the analogous racemic compound but without enough improvement to warrant attempts at optical resolution. DL-Try(C-11) was synthesized in amounts up to 325 mCi using a rapid, high-temperature, high-pressure modification of the Bücherer-Strecker amino acid synthesis. Yields ranged from 30--60%, and a total of 40 min was required for synthesis and chromatographic purification. DL-Try(C-11) thus appears to have significant potential as a clinical pancreas-imaging agent, particularly when used in conjunction with positron computerized transaxial tomography.

Adenocarcinoma↗
PubMed1978

Behavioral and physiological studies of non-narcotic analgesia in the rat elicited by certain environmental stimuli.

These experiments characterized the analgesia resulting from exposure to certain noxious and/or stressful manipulations. Rats exposed either to electric grid shock (0.35-2.0 mA for 10-30 sec) or to 5 min of presumably non-painful centrifugal rotation (about 7.0 transverse g's) were analgesic as measured by tail-flick, hot plate and responses to applications of a calibrated paw pinch or alligator clip. Analgesia produced by shock (SA) or centrifugal rotation (RA) persisted after termination of these manipulations. Neither SA nor RA were attended by generalized sensory, attentional or motoric deficits. Intraperitoneal injection of hypertonic saline also increased tail-flick latencies. Exposure to brief ether anesthesia or horizontal oscillation, both of which have been reported to increase ACTH secretion (a commonly used indicator of stress), did not produce analgesia as measured by the tail-flick test. The use of classical conditioning procedures to pair shock with environmental stimuli resulted in increased tail-flick latencies. The narcotic antagonist naloxone (1 mg/kg, i.p.) did not reduce the tail-flick inhibition produced by shock, rotation, hypertonic saline or classical conditioning. Chlordiazepoxide (5 mg/kg, i.p.) also failed to antagonize the increased tail-flick latencies produced by shock or conditioning. Tail-flick inhibition produced by shock or rotation was markedly reduced by complete spinal cord transection at thoracic levels. These results suggest that: (1) the selective modulation of nociceptive input at the level of the spinal cord can be mediated by a supraspinal system or systems physiologically distinct from those involved in analgesia produced by the administration of opiates; (2) non-narcotic modulation of nociceptive input occurring within the spinal cord can be learned by exposure to classical conditioning procedures; and (3) noxious stimuli are sufficient but not necessary to produce a non-narcotic analgesia; stress alone, however, is not always sufficient to produce this analgesia.

Analgesia↗
PubMed1978

Differential effects of spinal cord lesions on narcotic and non-narcotic suppression of nociceptive reflexes: further evidence for the physiologic multiplicity of pain modulation.

These studies examined the effects of bilateral lesions of the dorsolateral funiculus (DLF) of the rat spinal cord on the inhibition of a nociceptive reflex produced either by a systemic injection of 4 mg/kg of morphine or by a 20 sec exposure to 1.0 mA of transcutaneous electric shock. Reflex inhibition was quantified and analgesia inferred by use of a modified version of the D'Amour-Smith tail-flick test. Lesions which included only the DLF reduced morphine-produced analgesia (MA) by 73% but had no effect on shock-produced analgesia (SA) observed in the same rats. Baseline tail-flick latencies of this group were not affected by the lesions. Control lesions restricted to the dorsal columns attenuated neither MA nor SA. Lesions which included both the dorsal columns and DLF did not affect SA and produced no greater reduction in MA than lesions of the DLF alone. Previous work indicates that both MA and SA result, at least in part, from supraspinal activity. The current data indicate that: (1) supraspinal modulation participating in two different types of analgesic induction involves separate descending spinal pathways and (2) the maximal expression of analgesia produced by administration of narcotics requires the integrity of a supraspinal neural system projecting in the DLF.

Animals↗
PubMed1978

The medical use of gallium radionuclides: a brief history with some comments.

The use of gallium radionuclides in nuclear medicine dates back to the late 1940s, following the observation in toxicologic studies that gallium tended to localize to a high degree at sites of osteogenic activity. Initial attempts in the early 1950s to use 72Ga for clinical diagnosis and therapy of malignant bone lesions were unproductive. However, the basic information gained then in the preclinical and clinical investigations was quite instrumental in generating the present-day use of gallium radionuclides as effective radiopharmaceutical agents. Although initial clinical trials of 72Ga were unproductive, subsequent studies with 68Ga and 67Ga, together with advances in nuclear medical instrumentation, resulted in the identification of gallium radionuclides as effective tumor- and abscess-localizing agents. A major factor in the recognition of the peculiar biologic properties of gallium radionuclides was the existence of a carrier (stable isotope) effect. Also, it appears from basic studies of the mechanism(s) of the uptake of gallium in tumor tissue that the biodistribution of gallium involves many essential biologic processes. The future use of gallium radionuclides may, therefore, actually very well fall more into the field of basic biologic investigations rather than into the field of nuclear medical diagnosis.

Animals↗
PubMed1978

Effect of structure on tumor specificity of alicyclic alpha-amino acids.

The selective affinity of [carboxyl-11C]-1-aminocyclopentanecarboxylic acid (ACPC) for tumor tissue has led us to study the tumor-localizing characteristics of a series of alicyclic alpha-amino acid analogs of ACPC. The tissue distributions of [14C]-1-aminocyclopropanecarboxylic acid, 1-aminocyclobutanecarboxylic acid (ACBC), 1-aminocyclohexanecarboxylic acid, 1-amino-2-methylcyclopentanecarboxylic acid were compared with that of ACPC in Buffalo rats bearing Morris 5123C hepatomas. ACPC and ACBC were found to have significantly higher tumor-to-nontumor concentration ratios than the other four amino acids. ACBC generally had higher tumor-to-nontumor ratios than did ACPC, significantly so for muscle, kidney, and testis and marginally so for blood. These results suggest that [carboxyl-11C]ACBC may be a better agent than [carboxyl-11C]ACPC for tumor imaging by positron tomography.

Amino Acids↗