Search PubMed⌕ Search

Biomedical subjects

S M Larson

Publications and source records attributed to S M Larson.

317 records · Page 18Linked to original sources

Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer.

This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET) imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic (18)F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by (18)F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

Animals↗

Managing the difficult airway in patients with burns of the head and neck.

A five-phase defined protocol for airway security was developed and administered to a consecutive, selected series of surgical patients with burns to the head and neck that limited their mouth opening or neck mobility. The protocol uses fiberoptic light and scope systems to allow the anesthesia team to visually place the endotracheal tube properly before anesthesia is induced. The technique provides safe, efficient airway management for patients with burns to the head and neck and significantly diminishes patient risks.

Adolescent↗

Comparative anatomo-functional imaging of two neuroreceptors and glucose metabolism: a PET study performed in the living baboon.

Regional specialization of two types of neuroreceptor--opiate and dopamine--was mapped by positron emission tomography (PET) in the subcortical gray matter of the living baboon and analyzed in comparison with glucose metabolism. The three radiopharmaceuticals used--[18F]3-acetylcyclofoxy, [11C]3-N-methylspiperone, and [18F]2-fluoro-2-deoxyglucose--traced opiate- and dopamine-receptor distribution and regional glucose metabolism, respectively. A combination of high spatial resolution (6-7 mm) and the intrinsic sensitivity of the PET method made possible the detection of nanomolar concentrations of neuroreceptors and micromolar concentrations of metabolized glucose, with different and distinctive anatomo-functional distributions in thalami and basal ganglia.

Animals↗

MR imaging and positron emission tomography of cortical heterotopia.

Heterotopia of the gray matter is a developmental malformation in which ectopic cortex is found in the white matter of the brain. A case of a 33-year-old man with cortical heterotopia who had a lifelong history of seizures and psychomotor retardation is reported, including the results of cerebral CT, magnetic resonance imaging, and positron emission tomography using 18F-2-deoxyglucose.

Adult↗

Quantitative imaging of I-124 using positron emission tomography with applications to radioimmunodiagnosis and radioimmunotherapy.

Positron emission tomography (PET) is potentially useful for the quantitative imaging of radiolabeled antibodies, leading in turn to improved dosimetry in radioimmunotherapy. Iodine-124 is a positron-emitting nuclide with appropriate chemical properties and half-life (4.2 days) for such studies since the radiolabeling of antibodies with iodine is well understood and the half-life permits measurements over several days. Unfortunately, I-124 has a complex decay scheme with many high-energy gamma rays and a positron abundance of only 25%. It has therefore been largely ignored as a PET-imaging nuclide. However, measurements made with phantoms and animals under realistic conditions using a BGO-based PET scanner have shown that satisfactory imaging and quantitation can be achieved. Investigations of spatial resolution, the linearity of regional observed count rate versus activity in the presence of other activity, and the visualization and quantitation of activity in spheres with different surrounding background activities were carried out with phantoms up to 22 cm in diameter. Compared with F-18, spatial resolution was only slightly degraded (13.5 mm FWHM vs 12 mm FWHM) while linearity was the same over a 10:1 activity range (0.015 to 0.15 MBq/ml for I-124). The visualization and quantitation of spheres was also slightly degraded when using similar imaging times. Increasing the imaging time for I-124 reduced the difference. To verify that the technique would work in vivo, measurements were made of human neuroblastoma tumors in rats which had been injected with I-124 labeled 3F8 antibody. Although the number of samples was small, good agreement was achieved between image-based measurements and direct measurements of excised 4-g tumors. Thus quantitative imaging of I-124 labeled antibodies appears to be possible under realistic conditions.

Animals↗

Compassionate use of recombinant human thyrotropin to facilitate radioiodine therapy: case report and review of literature.

OBJECTIVE: To describe the use of recombinant human thyrotropin (thyroid-stimulating hormone) (rhTSH) to assist in radioiodine therapy in a patient with thyroid carcinoma who was unable to produce sufficient endogenous thyrotropin when hypothyroid and to review the related literature. METHODS: The study patient underwent formal dosimetric analysis and received radioiodine in conjunction with rhTSH. Follow-up scanning studies were performed. RESULTS: We found good localization of radioiodine on the posttherapy scans after administration of (131)I while the patient continued to receive thyroxine replacement after two intramuscularly administered injections of rhTSH. Some of his metastatic lesions disappeared and his serum thyroglobulin level decreased after the first rhTSH-assisted dose of (131)I was administered. His blood radioiodine clearance rate was unexpectedly more rapid in the hypothyroid state than when he was euthyroid (taking thyroxine) after administration of rhTSH. His whole-body clearance rate was more delayed when he was hypothyroid. Swelling of some of the metastatic thyroid cancer lesions developed when the patient was hypothyroid and after rhTSH was administered, the latter being much more rapid in onset. CONCLUSION: Therapeutic doses of radioiodine can be delivered with the assistance of rhTSH administration while patients continue to take suppressive doses of thyroxine. Metastatic thyroid carcinoma lesions can swell rapidly after administration of rhTSH. The commercially available form of rhTSH is approved only for diagnostic use. Its safety and efficacy in assisting radioiodine therapy have not been fully determined.

Adenocarcinoma, Follicular↗

A radiometric method for predicting effectiveness of chemotherapeutic agents in murine leprosy.

A simple radiometric method has been developed for evaluating the effect of drugs on the metabolism of M. lepraemurium. The method is based on the measurement of the 14CO2 produced through bacterial metabolism of acetate-U-14C. Seventeen drugs were tested: bacitracin, cephaloridine, chloramphenicol, cycloserine, dactinomycin, DDS, ethionamide, INH, kanamycin, methenamine mandelate, nitrofurantoin, oxacillin, polymyxin B, rifampicin, streptomycin, sulfadimethoxine and vancomycin. The drugs which caused most marked inhibition were chloramphenicol, INH, ethionamide and nitrofurantoin in order of increasing effectiveness. The radiometric study which is completed in 15 days permits direct study of the drug effect on the metabolism of M. lepraemurium and a more rapid screening of antileprosy drugs than has previously been possible. Currently, these observations are being extended to studies of the structure-activity relationships of antileprosy drugs and the metabolism and drug susceptibility of M. leprae in vitro.

Anti-Bacterial Agents↗

Radiometric studies of Mycobacterium lepraemurium.

The radiometric method has been applied for studying the metabolism of M. lepraemurium and the conditions which might force or inhibit its metabolic activity in vitro. These organisms assimilate and oxidize (U-14C) glycerol, and (U-14C) acetate, but are unable to oxidize (U-14C) glucose, (U-14C) pyruvate, (U-14C) glycine and 14C-formate. When incubated at 30 degrees C M. lepraemurium oxidizes (U-14C) acetate to 14CO2 faster than 37 degrees C. The smae effect was observed with increasing concentrations of polysorbate 80 (Tween 80), or the 14C-substrate. No change in metabolic rate was observed when the organisms were kept at -20 degrees C for 12 days. Although tried several times, it was not possible to demonstrate any "inhibitors" of bacterial metabolism in the reaction system. The radiometric method seems to be an important tool for studying metabolic pathways and the influence of physical and biochemical factors on the metabolism of M. lepraemurium in vitro.

Acetates↗

Transport limits cellular entry of hepatic arterially injected 5-[18F]fluoro-2'-deoxyuridine in human intrahepatic tumors.

The causes of tumor resistance to hepatic arterially infused fluorodeoxyuridine (FdUrd) are poorly understood. A previous study showed that sufficient arterial perfusion relative to liver is necessary for tumor response. The present study examined the effect of transport on FdUrd flux from arterial blood into tumor cells. Five patients with large intrahepatic tumors (four with colorectal hepatic metastases, one with hepatoma) were given bolus hepatic arterial (HA) injections of [18F]FdUrd, and their livers imaged dynamically with a dual-detector gamma camera. Cellular entry of [18F]FdUrd was inferred by comparison with HA-injected 99mTc diethylenetriaminepentaacetate, an extracellular indicator. The images were analyzed to determine single-pass, blood-into-cell, extraction fractions [E(FdUrd)] and fractional retention of extracted radiolabel vs. time in tumors and liver. Measured E(FdUrd) ranged from 0.75 to 0.91 (mean 0.87 +/- 0.03) in liver and from 0.56 to 0.96 (mean 0.78 +/- 0.08) in tumors. Fluorine-18 was lost from tumors and liver at similar rates following first-pass throughput of unextracted [18F]FdUrd. Less than 10% of the radiolabel remained in tumor or liver by 3.5 hr, implying that little 18F was incorporated into long-lived molecular species within tumor or liver. The observations indicate that, in many cases, limited transport significantly reduces the flux of FdUrd into the cells of intrahepatic tumors, implying that transport must be considered in efforts to increase tumor uptake of hepatic arterially infused FdUrd.

Aged↗