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Biomedical subjects

H L Atkins

Publications and source records attributed to H L Atkins.

At least 73 records · Page 4Linked to original sources

Some factors affecting the cerebral and extracerebral accumulation of N-isopropyl-p-iodo-amphetamine (IAMP).

The whole body distribution of IAMP was studied in mice, rats, rabbits, dogs and marmosets by tissue counting, scintigraphy and quantitative macroautoradiography. Identical distribution patterns of IAMP were observed in these species showing high concentration in the brain, lungs, eyes, liver and kidneys. Following the initial distribution, IAMP was released from the lungs and accumulated in the blood and liver. In the cerebrum the activity decreased with time whereas it progressively increased in the eyes and juxtamedullary region of kidneys. The effect of ACTH, propranolol and metopyrone (metyrapone, USP) on the distribution of IAMP was studied in normal mice. The distribution of IAMP in Dahl salt-sensitive hypertensive rats was compared to Dahl salt-sensitive normotensive rats. Blocking doses of potassium iodide (KI) in marmosets and rats did not affect the distribution pattern of IAMP. Carrier amphetamine in doses of up to 1.5 mg/kg also did not significantly alter the biodistribution of IAMP. When higher doses (up to 8.0 mg/kg) were given, the activity in the gut, lungs, and liver decreased but there was no effect on the uptake in the brain, kidneys, eyes, adrenals, muscle and spleen. This suggests a higher ratio of saturable to nonsaturable binding sites in the latter organs.

Adenosine Monophosphate↗

Thrombus radioimmunoscintigraphy: an approach using monoclonal antiplatelet antibody.

Thrombus detection and localization is of cardinal importance in clinical medicine. The currently available method using autologous 111In-labeled platelets is too lengthy and complex for everyday use. It requires careful separation of the platelets prior to labeling and visualization of the thrombus becomes possible only 24 hr after injection. An approach to thrombus imaging using a monoclonal antiplatelet antibody labeled with 111In or 123I is described. The antibody (7E3) prepared against human platelets inhibits the interaction between fibrinogen-coated beads and both human and dog platelets. 7E3 is an IgG1 that binds to the complexed glycoprotein IIb/IIIa. Ninety percent of a tracer dose of radiolabeled 7E3 binds to human platelets and 50% binds to dog platelets. In vitro studies showed that virtually all of the platelet-bound radioactivity becomes incorporated into clots formed by adding thrombin to whole blood. 7E3 was labeled with 111In by the cyclic anhydride diethylenetriaminepentaacetic acid method or by radioiodination with 123I. At a ratio of 1:50 (anhydride:7E3) the specific activity ranged between 10 and 40 muCi/micrograms (1 Ci = 37 GBq) without change in the antibody characteristics. In vivo studies in dogs were performed by preincubating for 1 hr the radiolabeled 7E3 with citrated blood or by directly injecting the radiolabeled 7E3 intravenously. Experimental thrombi were induced by transcatheter placement of copper coils into peripheral arteries and veins as well as in the superior vena cava and pulmonary artery. With gamma camera, visualization of venous and arterial thrombi as well as sites of intimal injury without visible thrombi, could be observed 1-1.5 hr after injection. There was no need for delayed imaging because of the fast clearance of radioactivity from the circulation nor was there need for blood pool subtraction. Two to 10-hr thrombi could be imaged but 48-hr thrombi were not detectable with this method. No change in platelet counts before and after the injection of labeled 7E3 nor increased bleeding tendency occurred. The advantages of this method are a shorter preimaging preparation time, faster visualization after injection, and no need for delayed imaging or subtraction techniques. For these reasons human investigations seem to be warranted.

Animals↗

Increased pulmonary technetium-99m DTPA accumulation in a patient with Goodpasture's syndrome.

Goodpasture's syndrome is characterized by the triad of glomerulonephritis, intra-alveolar pulmonary hemorrhage, and presence of antiglomerular basement membrane antibodies. It has been shown earlier that intra-alveolar hemorrhage can be detected with radioisotopic techniques. A patient with Goodpasture's syndrome showing increased pulmonary accumulation of Tc-99m DTPA with no evidence of pulmonary hemorrhage is presented.

Adult↗

Clinical comparison of two radiocolloids for internal mammary lymphoscintigraphy.

Recent studies suggest that 99mTc-labeled radiocolloid (SC) compounded with hydrogen sulfide can be used to visualize lymph channels and nodes. Our study prospectively compared SC with 99mTc antimony sulfide (SbS) colloid, in 28 patients undergoing internal mammary lymphoscintigraphy. Images were recorded on a scintillation camera and computer at 0.5, 1.0, and 3.0 hr. Quantitative analysis included assessment of percent (%) injected dose in nodes, the percent remaining at the injection site, and the relative intensity of the most cephalad node compared to a 57Co standard. The mean (means) % injected dose of both radiocolloids within visualized nodes was less than 1% at each time interval, with no significant differences between means's. The means % injected dose remaining at the injection site at 3.0 hr was 83 for SbS and 76 for SC not statistically significant (N.S.). The means of the ratio of counts within the most cephalad node at 3.0 hr to counts within a 57Co standard was 0.98 for SbS and 1.03 for SC (N.S.). Clinical assessment of number of nodes visualized and extent of radiocolloid migration showed no difference between the two agents. The biological and clinical parameters for the two colloids appear similar when used for internal mammary lymphoscintigraphy.

Adult↗

Myocardial uptake of a bone tracer associated with hypercalcemia.

A patient with end-stage renal disease and hypercalcemia was referred for a radionuclide bone imaging study. Deposition of Tc-99m hydroxymethylenediphosphonate was apparent in the lungs and myocardium as well as in the skeleton. Renal uptake was also noted, despite anuria. Computed tomography demonstrated nephrocalcinosis but no myocardial calcification. The cause of myocardial uptake of tracer is unknown. Amyloidosis is suggested as a possibility but is not validated in this case.

Acute Kidney Injury↗

Differential radioactivity monitor for noninvasive detection of ocular melanoma.

A novel instrument for the noninvasive diagnosis of ocular melanoma was evaluated with 67Ga in patients with pathologically confirmed tumours. The decision to enucleate was based on the results of standard ophthalmic diagnostic modalities including the 32P uptake test. The differences in the ocular radioactivity at 48-72 h predicted the presence of ocular abnormality. A positive differential result was found for tumours having a volume of greater than 600 mm3. Smaller tumours indicated lower retention of 67Ga in the eye with the tumour, whereas control subjects showed less than 2% differences in the radioactivity present in either eye.

Choroid Neoplasms↗

97Ru-transferrin uptake in tumor and abscess.

The uptake of 97Ru-transferrin (Ru-TF) in tumor and abscess bearing animals was compared with 67Ga-citrate (Ga), 123I-transferrin (I-TF), and several other plasma proteins. Maximal concentration in tumor of Ru-TF in mice was three times higher than 67Ga-citrate (16.80 +/- 4.20 vs 5.08 +/- 0.58% D/g) although it occurred later (24 h compared with 67Ga which reached its maximum 2 h after injection). Whole body autoradiography (WBARG) with 103Ru-transferrin (103Ru-TF) in tumor and abscess bearing rats demonstrated details of the distribution within these lesions. Turpentine-induced abscesses in the rabbits could be visualized with the gamma camera as early as 30 min post-injection of Ru-TF. It seems, therefore, that Ru-TF can be used for tumor and abscess localization. The results indicate that Ru-TF may have some advantages over 67Ga-citrate because of the higher concentration in the lesions. 123I-transferrin reached a concentration in tumor similar to 67Ga (6.89 +/- 1.67 vs 5.08 +/- 0.58% D/g) but had a very low tumor to blood ratio (0.64). The three compounds investigated (Ru-TF, I-TF and ionic Ga, which binds instantaneously to TF in vivo) have a common ligand, transferrin. It appears, therefore, that tumor affinity is a property of the radionuclide-ligand complex rather than of the radionuclide itself.

Abscess↗

Cyclotron isotopes and radiopharmaceuticals--XXXIII. Synthesis and structural effect of selective biliary excretion of halogenated indotricarbocyanines.

Five indotricarbocyanines of structure I were synthesized and labeled with 131I in the 5 position. The substituent, R, was varied [formula: see text] R = H, F, Cl, Br and I. The dynamics of hepatic uptake and blood clearance of the labeled compounds were determined in mice. Kidney uptake in all cases was negligible. The hepatic excretion displayed 2 components. The initial hepatic disappearance rates of R = H and R = F were 7.3 and 4.5%/min, respectively. The maximum liver activity in mice occurred at 2--5 min and the % remaining in the liver at 0.5 h was 3.6, 8.6, 19, 29 and 47% for R = H, F, Cl, Br and I substitution. It is notable that a small change in the substituent at the 5' position in the molecule has such a pronounced effect. Whether electronic and/or steric effects are controlling the mechanism of hepatobiliary clearance is not obvious. A correlation of the liver activity with the covalent radius of R was noted. The comparative studies were at an injected dose of 0.4--0.6 mumol/kg, and typically at a specific activity of 200 mCi/mol. Loading dose effects were not appreciable under these conditions. Scintigraphic results are reported for dogs and a rabbit. The results suggest that indotricarbocyanines of structure (I) labeled with 123I or with 18F are potential radiopharmaceuticals for dynamic hepatobiliary function studies.

Animals↗

Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocardial ischemia.

Sixteen asymptomatic patients with coronary artery disease and silent myocardial ischemia were studied with exercise radionuclide ventriculography. Radionuclide ventriculograms were analyzed for changes in ejection fraction globally and in three regions. Results were compared with radionuclide ventriculograms in 24 symptomatic patients. Both groups (silent myocardial ischemia and angina) were similar in prevalence of multivessel disease and previous myocardial infarction, as well as in age and sex. Global ejection fraction decreased by 0.06 in both groups during exercise; regional ejection fraction also decreased by similar amounts in the two groups. Furthermore, the percent of regions with normal ejection fraction at rest that demonstrated a decrease during exercise was identical: 19 (60%) of 33 versus 26 (60%) of 46. These exercise radionuclide ventriculographic results suggest that abnormalities in regional and global left ventricular wall motion are similar in patients with coronary artery disease with and without silent myocardial ischemia.

Angiography↗

Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma.

Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver and 100 for "back-ground" tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 microgram CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the 10B(n, alpha)7Li reaction.

Animals↗

Detection of gastrointestinal blood loss with 99mTc-labeled, heat-treated red blood cells.

Studies in dogs showed that heat-treated 99mTc-labeled red blood cells (HT/RBC) afford a highly sensitive means of detecting gastrointestinal bleeding as low as 0.12 ml/min., which could not be seen with unheated 99mTc-RBC, 99mTc-sulfur colloid, or 99mTc-DTPA. In addition, as the right upper quadrant and epigastrium remained free of activity, only one fifth to one tenth of the dose of 99mTc was needed. The safety of HT/RBC in humans has been documented, and the experiments in dogs suggest that it may have advantages over other agents in detecting gastrointestinal bleeding.

Animals↗

97Ru-DMSA for delayed renal imaging.

Dimercaptosuccinic acid (DMSA) was labeled with 97Ru both with and without the addition of SnCl.2H2O. The tin-containing preparation was found to induce higher cortical deposition of 97Ru-DMSA than the tin-free preparation. Visualization of the renal cortex was excellent 4 to 48 hours after injection in normal dogs with renal insufficiency. It is concluded that 97Ru-(Sn+2)-DMSA is a potentially useful renal imaging agent when delayed scintigraphy is necessary because of decompensaton of the kidneys.

Animals↗