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Biomedical subjects

K A Morton

Publications and source records attributed to K A Morton.

At least 19 recordsLinked to original sources
PubMed2004

Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [18F]4-fluorobenzyltrozamicol.

The pancreas is one of the most heavily innervated peripheral organs in the body. Parasympathetic and sympathetic neurons terminate in the pancreas and provide tight control of endocrine and exocrine functions. The aim of this study was to determine whether the pancreas can be imaged with a radioligand that binds to specific neuroreceptors. Using fluorine-18 4-fluorobenzyltrozamicol (FBT), which binds to the presynaptic vesicular acetylcholine transporter, positron emission tomography scans were performed in four adult mice, two adult rhesus monkeys, and one adult human. In these mammals, the pancreas is intensely FBT avid, with uptake greater than in any other organ at 30, 60, and 90 min. The maximum standardized uptake value (SUV) ratios of pancreas to liver, for example, ranged from 1.4 to 1.7 in rhesus monkeys (mean 1.6; median 1.7) and from 1.9 to 4.7 (mean 3.24; median 3.02) in mice. The maximum SUV ratio of pancreas to liver in the human was 1.8. These data suggest that neuroreceptor imaging of the pancreas in vivo is feasible in animal models and humans. This imaging could allow researchers to interrogate functions under control of the autonomic nervous system in the pancreas, with applications possible in transplanted and native pancreata. Also, as beta cell function is intimately related to parasympathetic cholinergic input, FBT activity in the pancreas may correlate with insulin-producing beta cell mass. This could ultimately provide a method of in vivo imaging in animal models and humans for diabetes research.

Animals↗
PubMed2001

Photodegraded nifedipine stimulates uptake and retention of iron in human epidermal keratinocytes.

Photodegraded nifedipine has been shown to increase uptake of nontransferrin bound iron into erythroid cells. If iron could be loaded into keratinocytes, it might be possible to exploit epidermal desquamation for the purpose of eliminating potentially toxic amounts of iron from the body. We investigated the ability of photodegraded nifedipine to stimulate iron transport and accumulation in human epidermal keratinocytes. Nifedipine was degraded to its nitroso derivative by exposure to sunlight. 59Fe uptake was measured in keratinocyte monolayers, and total iron content was measured in stratified epidermal cultures. Photodegraded nifedipine increased iron uptake into keratinocytes 80-fold compared to controls. The effect of photodegraded nifedipine on iron uptake was rapid, was concentration dependent and occurred at physiologically relevant concentrations of nonprotein-bound iron. Stimulation of iron uptake by photodegraded nifedipine was independent of transferrin and worked equally well in the presence or absence of serum proteins. Iron content in keratinocytes was increased 3-fold by four daily treatments with photodegraded nifedipine. The increased iron content resulting from photodegraded nifedipine treatment was retained during a 4 d washout period. Photodegraded nifedipine may be a way delivering clinically significant amounts of iron to the epidermis.

Cells, Cultured↗
PubMed2000

The effect of gadolinium contrast media on radioiodine uptake by the thyroid gland.

OBJECTIVE: Patients with thyroid cancer may require detailed anatomic imaging before 131I therapy. Imaging by contrast-enhanced CT is contraindicated because it may result in saturation of tissues with iodine, decreasing the avidity of thyroid or thyroid cancer cells to subsequent radioiodine for extended intervals. Gadolinium-enhanced MRI offers an alternative to CT for detailed anatomic imaging. However, it is not known whether gadolinium contrast affects uptake of iodine by the thyroid gland since lanthanides affect ion transport in a variety of ways. The objective of this project was to determine whether the gadolinium MRI contrast injection alters thyroid uptake of radioiodine. METHODS: Radioiodine uptake by the thyroid gland was measured at 6 h and 24 h after the oral administration of 100 microCi 123I-Na-I. Three to seven days later, a standard dose (20 mL) of Magnevist (gadolinium DTPA) was administered intravenously. Another capsule of 100 microCi 123I Na-I immediately was given orally, and 6-h and 24-h radioiodine uptake by the thyroid gland was again measured and compared to baseline values. RESULTS: There was no statistically significant difference in uptake of radioiodine uptake by the thyroid gland between baseline values and those acquired immediately after the administration of Magnevist. CONCLUSION: Contrast-enhanced MRI may be safely performed before contemplated determinations of thyroid uptake of radioiodine, 131I therapy for hyperthyroidism, and postsurgical 131I imaging and therapy for well-differentiated thyroid cancer.

Adult↗
PubMed2000

Gallium-67 imaging in lymphoma: tricks of the trade.

OBJECTIVE: Although the use of 18F-fluorodeoxyglucose (FDG) PET for evaluating lymphoma is gaining in popularity, PET is not yet universally available and large prospective comparisons between 67Ga and 18F-FDG PET scans in predicting the long-term outcome after treatment are lacking. Scintigraphic imaging with 67Ga remains an important tool in evaluating the response of lymphoma to therapy. There are a variety of challenges and pitfalls inherent in 67Ga imaging for lymphoma. These are discussed and problem cases are illustrated. After reading this article, the nuclear medicine professional should be able to: (a) optimize the technical approach to and (b) maximize the diagnostic accuracy of 67Ga scintigraphy in assessing the response of lymphoma to therapy.

Fluorodeoxyglucose F18↗
PubMed1999

Photodegraded nifedipine promotes transferrin-independent gallium uptake by cultured tumor cells.

UNLABELLED: It was reported previously that normal soft tissues accumulate 67Ga by a transferrin-dependent route, but uptake by tumors can be transferrin independent. It was also reported that, although overexpression of the transferrin receptor can promote Ga avidity, the transferrin-independent uptake of 67Ga is significant and can be augmented to exceed transferrin-mediated levels by increasing extracellular calcium. In assessing the effect of calcium channel blockers on uptake of 67Ga, it was observed that, after exposure to light (either visible or ultraviolet [UV]), nifedipine strongly potentiates the cellular uptake of 67Ga by a transferrin-independent process. METHODS: The effect of nifedipine on 67Ga uptake as a function of time, concentration, duration and type of preexposure to light was determined in two cultured Chinese hamster ovary cell lines. One cell line lacks the transferrin receptor. In the other, the human transferrin receptor has been restored by transfection and is overexpressed constitutively. RESULTS: Although there are some differences in pattern of stimulation of uptake, nifedipine subjected to either UV or fluorescent light strongly promotes the uptake of 67Ga in the cultured cells in a time-dependent and concentration-dependent manner. Maximal uptake of 67Ga occurs when the cells are incubated for 30 min with 25 micromol/L nifedipine preexposed to either 4h of fluorescent or 1h of UV light. Under these conditions, uptake of 67Ga is 1000-fold greater than basal levels and 50-fold greater than can be achieved by the transferrin-dependent route. Light-shielded nifedipine has no effect on 67Ga uptake. CONCLUSION: The effect of photodegraded nifedipine on the uptake of 67Ga is independent of expression of the transferrin receptor. The potential for photodegraded nifedipine to improve oncologic imaging with 67Ga warrants further investigation.

Animals↗
PubMed1998

Uptake of gallium-67 in transfected cells and tumors absent or enriched in the transferrin receptor.

UNLABELLED: Gallium-67 has been a controversial tumor-imaging agent in nuclear medicine for decades. This controversy centers on why tumors are variable in gallium-avidity, whether 67Ga uptake is a transferrin-independent or dependent process, and whether tumors and normal tissues differ in mechanism of uptake. If the factors that control uptake of 67Ga were understood better, then efforts to improve oncologic imaging with 67Ga by increasing the tumor activity, or by decreasing the background, may be warranted. METHODS: Conventional systems for evaluating the mechanism and control of 67Ga uptake have significant limitations. We have endeavored to circumvent these by developing a pair of transfected cell lines. One cell line has no transferrin receptor. In the other, the human transferrin receptor has been restored by transfection and is over-expressed constitutively, without the necessity to manipulate factors such as cell growth or iron content. The uptake of 67Ga, both as a citrate salt and as a gallium-transferrin complex, was examined in these pairs of cells in vitro. The effect of calcium and of soluble (ionic) iron concentration on 67Ga uptake also was determined. Tumors were grown as explants of these cells in nude mice and comparisons of uptake of 67Ga by these tumors in vivo were made. RESULTS: The in vivo uptake of 67Ga is significantly increased in tumors in which the transferrin receptor is overexpressed, compared to those without a functional transferrin receptor. However, a notable amount of accumulation of 67Ga also occurs, both in vitro and in vivo, by a transferrin-independent route. In vitro experiments demonstrate that the uptake of 67Ga by the transferrin-independent route can be enhanced further to levels that equal or exceed those achieved by the transferrin-dependent route by increasing the content of calcium or iron salts in the incubation medium. CONCLUSION: Significant transferrin-independent uptake of 67Ga occurs both in vitro and in vivo. This uptake can be stimulated further in vitro, suggesting that in vivo enhancement might also be possible to enhance the utility of the radiometal for tumor imaging.

Animals↗
PubMed1997

Determination of glomerular filtration rate using technetium-99m-DTPA with differing degrees of renal function.

UNLABELLED: Glomerular filtration rate (GFR) is an important index of renal function. Twenty-four-hour creatinine clearance overestimates GFR in patients with poor renal function. Inulin and iothalamate clearances are accepted reference standards for determining GFR but are expensive and laborious. We have previously reported that GFRs obtained by measuring the disappearance of 99mTc-DTPA from ultrafiltered (protein-free) samples of plasma were virtually identical to those obtained by the iothalamate method. However, the subjects used in that study had normal to only moderately decreased renal function. METHODS: The accuracy of measuring GFR by plasma clearance of 99mTc-DTPA was determined in subjects where renal function varied from normal to severely impaired. In all subjects, GFR was established by clearance of 125I-iothalamate from urine and serum and was used as the standard of reference. RESULTS: For subjects with normal to moderately diminished renal function (GFR > 20 ml/min), the correlation between values of GFR obtained by the DTPA and iothalamate methods was high (n = 18, r = 0.966). The difference between the pairs of GFR values obtained by the two methods was not statistically significant (p > 0.1). In patients with severe renal insufficiency (GFR < 20 ml/min), the correlation between the DTPA and iothalamate methods was poor (n = 11, r = 0.236), and the GFR values obtained by the two methods were statistically different (p < 0.01). CONCLUSION: These results suggest that GFR can be determined accurately by plasma clearance of 99mTc-DTPA in all patients except those with severe renal insufficiency.

Adult↗
PubMed1995

Biodistribution and dosimetry of indium-111-polyclonal IgG in normal subjects.

UNLABELLED: Indium-111-polyclonal IgG is a new imaging agent of infection and inflammation that has been developed as a possible replacement for radiolabeled leukocytes. We undertook a study to determine the safety, biodistribution and dosimetry of the agent in normal subjects. METHODS: Twelve normal male volunteers with an average age of 34 yr (range 21-55 yr) were studied. Each was injected with 1.22-1.47 mCi 111In-labeled polyclonal IgG; digital whole-body images, in addition to blood, urine and fecal samples, were obtained immediately after injection and at 6, 24, 48, 72, 96 and 120 hr. Whole-body counts, as well as individual organ data obtained by outlining regions of interest, were measured. Blood, urine and fecal counting were done in a well counter and compared to known standards; dosimetry calculations were performed with the MIRD technique. RESULTS: The mean whole-blood activity had a two-phase disappearance curve: the T1/2I was 11.4 hr (61.1%) and the T1/2II was 112.5 hr (38%). Twelve percent of the dose was excreted in the urine and 1.14% in the feces. Skeletal muscle had the highest percentage of uptake, followed by the bone marrow, liver and lungs; the spleen showed less than 1% uptake. Activity in the lungs varied with time, falling by 37% after 18 hr and by 68% after 72 hr. Dosimetry calculations indicated that the highest absorbed dose was to the liver (1.42 rad/mCi) followed by the testes (1.23 rad/mCi) and red marrow (0.976 rad/mCi). The total-body dose was 0.467 rad/mCi, with an effective dose equivalent of 790.84 mrem. CONCLUSION: The biodistribution of 111In IgG is similar to that of 99mTc-HMPAO-labeled leukocytes. Activity in the liver, kidneys and GI tract may make evaluation of infection in these regions difficult. The dosimetry data indicate that adequate doses can be administered for clinical imaging without exposing the patient to excessive radiation.

Adult↗
PubMed1994

Scintigraphic appearance of bone during external beam irradiation.

Separate imaging studies employing Tc-99m MDP, In-111 labeled leukocytes, and Tc-99m SC were performed in a patient receiving external beam radiation therapy to the mediastinum and left hemithorax. The leukocyte scan demonstrated greatly increased activity at the site of the radiation port. The bone marrow (sulfur colloid) scan was normal and the bone scan demonstrated only minimally increased activity in the irradiated region. The varying appearance of these scans may represent the difference in the early effect of radiation on bone and bone marrow elements.

Bone Marrow↗
PubMed1994

Bilateral fatigue fractures of the radial shaft in a gymnast.

A 24-year-old female gymnast had a 3-month history of bilateral forearm pain. A Tc-99m MDP bone scan demonstrated focally increased activity in the radial shafts on blood pool and delayed images, characteristic of fatigue fractures. Fatigue fractures commonly occur in the lower extremities. Upper extremity fatigue fractures, in contrast, are uncommon and usually involve the humerus or ulna. Fatigue fracture of the radial shaft from gymnastic exercise has not been previously reported.

Adult↗
PubMed1994

The efficacy of indium-111-polyclonal IgG for the detection of infection and inflammation.

UNLABELLED: The purpose of this study was to determine the efficacy of 111In-polyclonal immunoglobulin (IgG) for the diagnosis of infection or inflammation. METHODS: Fifty-three patients with suspected infection were prospectively studied. Each underwent an 111In-polyclonal IgG study; biopsy, surgery, additional nuclear medicine scans and radiographic studies were used to confirm the IgG scan results. RESULTS: The polyclonal IgG scan had a sensitivity of 97.9% and a specificity of 94% for infection or inflammation. When only infection or severe inflammation such as bowel infarction was considered, the sensitivity remained the same but the specificity fell to 83%. Chronic infections were detected equally as well as acute infections. Antibiotics, steroids, anti-inflammatory agents, diabetes and diminished renal function did not affect scan sensitivity. There were no adverse reactions to the radiopharmaceutical. Three patients underwent extended imaging. Their scans stayed positive for an average of 8 days. Three patients treated for infection had their scans turn negative on repeat study, confirming the efficacy of their antibiotic therapy. CONCLUSION: Indium-111-polyclonal IgG is an effective imaging agent of infection and/or inflammation that is useful in a variety of infections and in severe inflammatory diseases. The ease of preparation and safety make it an attractive alternative to labeled leukocytes.

Adult↗
PubMed1993

The sequence of the Haemophilus influenzae mutB gene indicates it encodes a DNA helicase II-like protein.

A 6.2-kb Haemophilus influenzae genomic DNA fragment which partially complemented both the mutator and ultraviolet light sensitive (UVs) phenotypes of the H. influenzae mutB1 mutant was isolated. This fragment was also able to complement the UVs phenotype of Escherichia coli uvrD mutant hosts. The uvrD+ gene complemented the mutator phenotype of mutB1 hosts. The nucleotide (nt) sequence of the 6.2-kb fragment revealed an open reading frame (ORF) of 2184 bp. This ORF shows similarity at both the nt and amino acid (aa) levels with the uvrD gene of E. coli. Comparison of the sequences revealed eight regions of aa conservation in addition to seven previously identified helicase superfamily domains. The nt sequence 5' to the mutB ORF contains several potential regulatory motifs, including a LexA-binding site. Based upon these observations, we are confident that the mutB gene of H. influenzae encodes an ATP-dependent DNA helicase-like activity.

Adenosine Triphosphatases↗
PubMed1993

The use of computer-assisted diagnosis in cardiac perfusion nuclear medicine studies: a review (Part 2).

Computer-assisted diagnosis (CAID) is commonly used to evaluate cardiac nuclear medicine studies such as thallium perfusion scans. Part I of this series (Journal of Digital Imaging, Vol 5, No 4, pp 209-222) reviewed the basic theory underlying CAID in nuclear medicine and its use in planar thallium imaging. This review discusses the application of CAID to SPECT perfusion studies.

Artifacts↗
PubMed1993

The use of computer-assisted diagnosis in cardiac perfusion nuclear medicine studies: a review (Part 3)

Computer-assisted diagnosis (CAID) is commonly used to evaluate cardiac nuclear medicine studies such as thallium perfusion scans. Part 1 of this series (Journal of Digital Imaging, 5:209-222, 1992) reviewed the basic theory underlying CAID in nuclear medicine and its use in planar thallium imaging. Part 2 discussed the application of CAID to SPECT perfusion studies (Journal of Digital Imaging, 6:1-15, 1993). This article reviews new variations of CAID programs for SPECT imaging and the application of expert systems and neural networks to CAID of nuclear medicine perfusion studies.

Algorithms↗
PubMed1993

Comparison of methods for identifying early methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis.

Hepatotoxicity may complicate therapy with methotrexate in patients with rheumatoid arthritis. Prevention of cirrhosis may depend upon early identification of liver damage, usually accomplished by serial biopsy. To determine the adequacy of noninvasive methods for identifying hepatotoxicity, 22 sets of data were obtained in patients undergoing therapy with methotrexate for rheumatoid arthritis. Comparisons were made between liver biopsy, hepatocellular enzymes and two noninvasive radioisotopic methods that have been shown to be abnormal in hepatocellular disease: the rate constant of excretion of the 14C-aminopyrine and the time from injection to peak hepatic activity of 99mTc-diisopropylimidodiacetic acid. The hepatocellular enzymes and the time-to-peak-activity of diisopropylimidodiacetic acid were not useful predictors of methotrexate-induced hepatotoxicity. The aminopyrine breath test was abnormal in approximately half the patients with hepatotoxicity but showed poor specificity. Noninvasive methods remain inferior to biopsy for the detection of mild to moderate methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis.

Adult↗