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Biomedical subjects

H L Atkins

Publications and source records attributed to H L Atkins.

At least 37 records · Page 2Linked to original sources

Tin-117m(4+)-DTPA for palliation of pain from osseous metastases: a pilot study.

UNLABELLED: The physical and biological attributes of 117mSn(4+)-DTPA indicate that it should be an effective agent for palliative therapy of painful bony metastatic disease. The aim of this study was to evaluate whether or not this agent could effectively reduce pain while sparing the hemopoietic marrow from adverse effects. METHODS: Fifteen patients (10 males and 5 females) with painful bony metastases from various primary cancers were included in the study. Seven patients received 1.22 to 3.11 MBq/kg of 117mSn intravenously (Group 1) and eight patients received 4.85 to 5.77 MBq/kg (Group 2). All but one were treated as outpatients and followed for a minimum of 2 mo. RESULTS: In the first group, pain relief was non-assessable in four patients because of death or additional treatment of soft-tissue disease by another modality. One patient had no relief of pain, one had complete relief of pain and one had transient relief of pain. No myelotoxicity was observed. For Group 2, three patients achieved complete relief of pain, two good relief, two partial relief and one began to experience pain relief when he suffered a pathological fracture 2 mo post-treatment. None of these patients had myelotoxicity. CONCLUSION: Tin-117m(4+)-DTPA can reduce pain from metastatic disease to bone without inducing adverse reactions related to bone marrow. Further studies are needed to assess tolerance levels for the bone marrow and to evaluate response rates and duration of effect.

Bone Marrow↗

Radiation exposure to human trachea from xenon-133 procedures.

UNLABELLED: The general dosimetry of 133Xe for human studies is well documented, but the resultant radiation exposure to tracheal tissue is poorly known. This organ is of central relevance because the tracer is primarily eliminated through exhalation. METHODS: We report actual 133Xe concentrations in respiratory air during measurement of regional cerebral blood flow (rCBF), when the tracer is administered both by inhalation and intravenous injection. Data were collected from 102 patients, with equal gender representation and an age range of 18-82 yr. Most of the patients had subarachnoid hemorrhage or Alzheimer's disease or were normal control subjects. Average administered doses were 18 +/- 4 mCi by inhalation and 15 +/- 3 intravenously. RESULTS: We found average respiratory concentrations of about 1.80 mCi/liter during a 1-min inhalation and 0.74 mCi/liter following intravenous injection of standard doses. These activities drop rapidly: average respiratory concentrations during the second minute are 0.70 mCi/liter for inhalation and 0.19 mCi/liter for intravenous injection and reach negligible levels thereafter. We calculate that the tracheal absorbed dose from 133Xe procedures is approximately 28 mrad following inhalation and about 11 mrad following intravenous injection. These values reflect the full 11-min exposure, but most of the activity is only present initially. CONCLUSION: These values will agree with previous estimates and indicate an excellent safety margin.

Administration, Inhalation↗

Assessment of left ventricular enlargement from planar thallium-201 images.

Although a subjective assessment of left ventricular (LV) size can be made from planar thallium images, the validity of this practice had not been critically assessed. The objective of this study was to determine the accuracy of planar thallium imaging in the assessment of LV size by using two-dimensional guided M-mode echocardiographic measurements as the standard. Consecutive patients (n = 100) who had clinically indicated stress thallium and echocardiography done within a time interval of 1 month were selected. LV size was classified as dilated or normal on immediate and 4-hour-delayed thallium scans by the consensus of two blinded observers. When present, perfusion defects were noted. LV end-diastolic internal diameter (LVIDd) was measured on M-mode images. The mean LVIDd was 5.7 cm in patients with dilated LVs compared with 5.0 cm in those with normal LVs (p < 0.01). By using an LVIDd of 5.6 cm as the upper limit of normal, the sensitivity and specificity of planar thallium imaging for detection of left ventricle enlargement were 87% and 86%, respectively. Corresponding positive and negative predictive accuracies in this population were 65% and 96%, respectively. There was a higher incidence of fixed defects in group 1 (p < 0.01). We conclude that LV enlargement can be easily and reliably determined from routine planar thallium images.

Echocardiography↗

Pinhole SPECT: an approach to in vivo high resolution SPECT imaging in small laboratory animals.

UNLABELLED: The performance of pinhole SPECT and the application of this technology to investigate the localization properties of radiopharmaceuticals in vivo in small laboratory animals are presented. METHODS: System sensitivity and spatial resolution measurements of a rotating scintillation camera system are made for a low-energy pinhole collimator equipped with 1.0-, 2.0- and 3.3-mm aperture pinhole inserts. The spatial detail offered by pinhole SPECT for in vivo imaging was investigated in studies of the brain and heart in Fisher 344 rats by administering 201TICI, 99mTc-HMPAO, 99mTc-DTPA and 99mTc-MIBI. Image acquisition is performed using a rotating scintillation camera equipped with a pinhole collimator; projection data are acquired in conventional step-and-shoot mode as the camera is rotated 360 degrees around the subject. Pinhole SPECT images are reconstructed using a modified cone-beam algorithm developed from a two-dimensional fanbeam filtered backprojection algorithm. RESULTS: The reconstructed transaxial resolution of 2.8 mm FWHM and system sensitivity of 0.086 c/s/kBq with the 2.0-mm pinhole collimator aperture provide excellent spatial detail and adequate sensitivity for imaging the regional uptake of the radiopharmaceuticals in tumor, organs and other tissues in small laboratory animals. CONCLUSION: The resolution properties of pinhole SPECT are superior to those which have been achieved thus far with conventional SPECT or PET imaging technologies. Pinhole SPECT provides an important approach for investigating localization properties of radiopharmaceuticals in vivo.

Animals↗

Biodistribution of Sn-117m(4+)DTPA for palliative therapy of painful osseous metastases.

Tin-117 has certain physical characteristics (half-life of 13.6 days, low-energy-conversion electrons, gamma photon of 158.6 keV) that suggest that it may be a favorable agent for radionuclide therapy. It has been shown in animal models that Sn-117m in the chemical form Sn(4+)diethylenetriaminepentaacetic acid localizes selectively in bone. The authors therefore studied its whole-body distribution in 10 patients to obtain absorbed dose estimates for therapy. The results showed that more than 50% of the administered activity was absorbed in the bones of patients with metastatic carcinoma. Retention was determined primarily by radioactive decay. For adult men, the radiation absorbed dose estimate averaged 54.8 mGy/MBq (203 rad/mCi) to bone surfaces and 6.1 mGy/MBq (22.6 rad/mCi) to the red marrow. All other tissues received less than 1/10 of the dose received by red marrow. These results suggest that a clinical therapeutic trial should be attempted.

Adult↗

SPECT and planar brain imaging in crack abuse: iodine-123-iodoamphetamine uptake and localization.

The uptake, distribution, and clearance properties of 123I-IMP in the brain were evaluated in controls and asymptomatic crack users to investigate cerebral blood flow alterations in crack abuse. Serial dynamic planar images of the brain (0-25 min), SPECT of the brain (0.5 hr and 4 hr) and whole-body scans (75 min) were obtained in 21 crack abusers and 21 control subjects. Major observations include: (a) foci of abnormally reduced 123I-IMP activity mainly in the frontal and parieto-occipital cortex or marked irregularities in the uptake of 123I-IMP throughout the cerebral cortex consistent with moderate to severe disruption in regional cerebral blood flow were observed on the 0.5 hr SPECT images of 16/21 asymptomatic crack users; (b) no correlation could be demonstrated between the incidence or severity of SPECT perfusion abnormality with the frequency, amount or length of time of crack use; (c) focal perfusion defects observed in 6/21 crack users on the 0.5-hr SPECT images partially or completely filled-in on delayed SPECT at 4 hr in four of six subjects; (d) the rate of cerebral uptake of 123I-IMP in crack users averaged 23% less than observed in control subjects over the first 25 min after tracer administration; and (e) 123I-IMP activity reaching the brain of cigarette smoking control subjects (n = 14) at 25 min after injection averaged 42.5% less than in nonsmoking controls (n = 7). Quantitative measurements of the uptake and distribution properties of 123I-IMP in the brain proved to be an objective, sensitive and useful measure of regional cerebral blood flow in crack abuse.

Adult↗

Characterization of the structure of the erythropoietin receptor by ligand blotting.

Erythropoietin (Epo) regulates the growth and differentiation of erythroid cells by binding to a specific receptor. We characterized the native Epo receptor on erythroleukemia cell lines by ligand blotting. Solubilized cell membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred onto nitrocellulose, and probed with 125I-Epo. Specificity was demonstrated by inhibition of 125I-Epo binding by unlabeled excess Epo but not other peptide growth factors and by the cellular distribution of the Epo binding protein. A single membrane protein of 61 Kd +/- 4 Kd was sufficient to bind 125I Epo in both human (OCIM2, K562) and murine (GM979, Rauscher, DA-1) cell lines. This finding is consistent with the predicted size of the Epo receptor from the murine cDNA clone. However, chemical crosslinking of 125I-Epo to its receptor has identified two Epo binding proteins of 105 Kd and 85 Kd. This difference may occur because the receptor is size fractionated before Epo binding in the ligand blot, but after Epo binding in crosslinking studies. Ligand blotting demonstrates that the native Epo receptor is composed of a single 61-Kd Epo binding protein, and suggests the presence of additional proteins of 20 to 25 Kd that associate with the receptor after Epo binding.

Animals↗

Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor.

We have cloned a partial cDNA encoding murine stem cell factor (SCF) and show that the gene is syntenic with the Sl locus on mouse chromosome 10. Using retroviral vectors to immortalize fetal liver stromal cell lines from mice harboring lethal mutations at the Sl locus (Sl/Sl), we have shown that SCF genomic sequences are deleted in these lines. Furthermore, two other mutations at Sl, Sld and Sl12H, are associated with deletions or alterations of SCF genomic sequences. In vivo administration of SCF can reverse the macrocytic anemia and locally repair the mast cell deficiency of Sl/Sld mice. We have also provided biological and physical evidence that SCF is a ligand for the c-kit receptor.

Amino Acid Sequence↗

The scintigraphic pattern of renal angiomyolipoma.

The patterns of renal and gallium scintigraphy in a patient with renal angiomyolipoma are presented. Renal study with Tc-99m DTPA demonstrated a photopenic area in the flow and delayed images. Ga-67 citrate imaging did not show any evidence of increased activity. Although this pattern is also seen in renal cysts, scintigraphy seems to be valuable in the evaluation of angiomyolipoma. It helps differentiate it from renal carcinoma or renal abscess (which may be gallium avid), especially when the tumor is characterized by a paucity of adipose tissue and complicated by hemorrhage, in which case CT and ultrasonographic patterns are not diagnostic.

Abscess↗

The role of factor analysis in the evaluation of new radiopharmaceuticals.

Factor analysis of dynamic scintigraphic studies has been proposed for a variety of clinical applications. This method also called FADS (Factor Analysis of Dynamic Structures) enables spatial separation of complex images into discrete factors according to their time/activity characteristics. FADS, which does not require a priori formulation of a compartmental model of tracer kinetics, is particularly suitable for the evaluation of new radiolabeled compounds as potential radiopharmaceuticals. In animals as well as in humans it is possible to obtain information on the spatial time-distribution of tracers by analyzing computer acquired scintigraphic studies. On the basis of data obtained and analyzed with this method using [123I]IMP in humans, dogs, rabbits and rats, with two 99mTc labeled monoclonal antibodies in dogs and with 99mTc DTPA in renal transplants, we recommend this method as an adjunct in radiopharmaceutical development and evaluation.

Amphetamines↗

Quantitative evaluation of renal excretion on the dynamic DTPA renal scan.

In order to evaluate the renal excretion quantitatively, the authors analyzed the Tc-99m DTPA renogram using mean transit time (MTT) with deconvolution analysis and compared it to the perfusion index. One hundred thirteen studies consisting of 25 normal, 11 obstruction, 35 transplant-norm, 12 transplant-obstruction, and 30 transplant-rejection were evaluated. In the non-transplant obstruction, MTT is significantly long (3.40 +/- 0.85 minutes vs 2.02 +/- 0.42 minutes) and has high sensitivity (100%) and specificity (93%, 23/25) for the diagnosis of obstruction. In the transplant-obstruction, if the field of view includes both transplant and liver or spleen as a blood pool image, MTT has high sensitivity for the diagnosis (10/11) and for the follow up of obstruction (12/12), with the same specificity, but low sensitivity for rejection (25%). Perfusion index is of value in the diagnosis of rejection (73% specificity, 77% sensitivity) but is useless for the detection of obstruction (25% specificity, 75% sensitivity). The authors conclude that MTT is a useful marker for diagnosis and serial quantitative evaluation of renal obstruction. Also, they suggest the use of multiple techniques based on different principles for the complete evaluation of the renal scan.

Humans↗

Asymmetric gallbladder contraction following cholecystokinin hepatobiliary imaging.

Three patients are presented with abnormal hepatobiliary images. A slow infusion of the terminal octapeptide of cholecystokinin caused asymmetric contraction in all three. Two of the patients displayed a bilobate appearance of the gallbladder. In one of the patients, there were typical changes associated with adenomyomatosis by other imaging modalities. The third patient showed good contraction of the fundus of the gallbladder but not of the proximal segment. In two of the patients, the global ejection fraction was considered to be normal. The asymmetrical contraction under the stimulus of cholecystokinin may be an important indicator of biliary dysfunction despite a normal ejection fraction.

Adolescent↗