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Biomedical subjects

P Som

Publications and source records attributed to P Som.

At least 55 records · Page 3Linked to original sources

Anti-colon/ovarian tumor antigen: localization of colon cancer xenografts in athymic rats.

Tumor localization studies in athymic rats bearing human colon tumors were performed using the radioiodinated monoclonal antibody SP-21 and its F(ab')2. Antibody preparations isolated from ascitic fluid and antibody from bioreactor effluent were used in these studies with similar radioimmunolocalization results. The intact antibody had an optimal localization time of 4-8 days after injection, while the F(ab')2 fragments had an optimal localization time of 3-4 days. Whole-body autoradiography, whole-body immunohistochemistry, and scintigraphy confirmed that the intact antibody and the antibody fragments localized preferentially in the tumor. The antibody distribution within the tumor was uniform, and not confined to the periphery, nor to focal areas within the tumor. Dose-response studies were performed with the intact antibody over a range of 10-100 micrograms/kg of total body weight with no clear-cut relationships observed. Comparisons of different radio-iodination methods indicated that the chloramine-T-based methods resulted in preparations with higher tumor uptake.

Animals↗

Detection of cardiomyopathy in an animal model using quantitative autoradiography.

A fatty acid analog (15-p-iodophenyl)-3,3 dimethyl-pentadecanoic acid (DMIPP) was studied in cardiomyopathic (CM) and normal age-matched Syrian hamsters. Dual tracer quantitative wholebody autoradiography (QARG) with DMIPP and 2-[14C(U)]-2-deoxy-2-fluoro-D-glucose (FDG) or with FDG and 201Tl enabled comparison of the uptake of a fatty acid and a glucose analog with the blood flow. These comparisons were carried out at the onset and mid-stage of the disease before congestive failure developed. Groups of CM and normal animals were treated with verapamil from the age of 26 days, before the onset of the disease for 41 days. In CM hearts, areas of decreased DMIPP uptake were seen. These areas were much larger than the decrease in uptake of FDG or 201Tl. In early CM only minimal changes in FDG or 201Tl uptake were observed as compared to controls. Treatment of CM-prone animals with verapamil prevented any changes in DMIPP, FDG, or 201Tl uptake. DMIPP seems to be a more sensitive indicator of early cardiomyopathic changes as compared to 201Tl or FDG. The trial of DMIPP and SPECT in the diagnosis of human disease, as well as for monitoring the effects of drugs which may prevent it seems to be warranted.

Animals↗

Quantitative neutron capture radiography for studying the biodistribution of tumor-seeking boron-containing compounds.

Biodistribution of two compounds presently considered for use in neutron capture therapy has been studied in mice carrying a transplantable Harding-Passey melanoma. A method is described by which quantitative assessment can be made of the boron distribution in whole-body sections of such animals. An alpha-particle-sensitive film is placed in close contact with a freeze-dried section of an animal and exposed to neutrons. The tracks visible after etching are analyzed optoelectronically in fields of 0.6 X 0.6 mm2 and compared to standards of boron homogeneously distributed in liver homogenates. The dynamic range of this method is about two orders of magnitude in concentration, with a lower detection limit of 0.1 to 0.01 ppm 10B, depending on the rate of induction of spurious tracks by fast neutrons present in the neutron beam chosen. In a transplantable Harding-Passey melanoma in mice, it was found that the sulfhydryl boron hydride Na2B12H11SH presently used for therapy of glioblastoma clears blood, muscle, and brain very rapidly. Its accumulation in tumors was persistent for more than three days. A higher tumor accumulation was observed with its disulfide, which has been suggested for neutron capture therapy. For both compounds, a marked heterogeneity of boron distribution within one tumor was found.

Animals↗

Dual tracer autoradiographic study of beta-methyl-(1-14C) heptadecanoic acid and 15-p-(131I)-iodophenyl-beta-methylpentadecanoic acid in normotensive and hypertensive rats.

The myocardial distribution of 15-p-[131I]iodophenyl-3-(R,S)-methylpentadecanoic acid (BMPDA) and 1[14C]-3-(R,S)-methylheptadecanoic acid (BMHDA) was compared in normotensive and hypertensive rats using quantitative dual tracer autoradiographic techniques. The myocardial distribution of carbon-14 [14C] BMHDA and iodine-131 [131I] BMPDA was nearly homogeneous in the normotensive rats, while both tracers showed similar, though very heterogeneous, distribution in hypertensive hearts with decreased uptake in the endocardial region. Our data demonstrate that myocardial distribution of [131I]BMPDA was essentially the same as [14C]BMHDA, and thus single photon emission computed tomographic imaging with 123I-labeled BMPDA could be useful for the detection of regional changes of myocardial fatty acid uptake in patients with prolonged and severe hypertension.

Animals↗

Radioimmunoimaging of experimental thrombi in dogs using technetium-99m-labeled monoclonal antibody fragments reactive with human platelets.

Monoclonal antibody 50H.19, which reacts with human platelets, was converted to fragments, pretinned, and made into kits for subsequent radiolabeling with 99mTc. The antibody, which cross-reacts with dog platelets, was used to evaluate in vitro binding to blood clots and in vivo in experimental thrombi in dogs. After radiolabeling, 97.4 +/- 6.4% of the 99mTc was antibody-associated. The preparations retained immunoreactivity, as determined by: binding studies using whole blood and determining the ratio of cell-to-plasma radioactivity (ratios of 57.6-61.2) and binding of the antibody to clots (clot/serum ratios were 57.2-74.6%). Approximately 50% of the radioactivity was cleared from the blood in 3-6 min and 18-24% was excreted in urine within 3 hr. Experimental thrombi in dogs could be visualized consistently within 2-3 hr postinjection in peripheral veins and arteries, pulmonary arteries, and the right ventricle. In addition, damage to blood vessel intima without visible thrombi could also be detected. This method has the following advantages: short and simple pre-imaging preparation, and rapid visualization of thrombi with no need for blood-pool subtraction or delayed imaging.

Animals↗

Quantitative whole-body autoradiography of radiolabeled antibody distribution in a xenografted human cancer model.

Quantitative whole-body autoradiography (WBAR) was used to study the biodistribution of goat anti-carcinoembryonic antigen and normal goat IgG, each labeled with 125I, in hamsters bearing the carcinoembryonic antigen-producing GW-39 human colonic carcinoma xenograft. Comparisons between computer-assisted videodensitometric profiles of WBARs and tissue radioactivity counts were made at 1, 3, and 7 days following administration of the radiolabeled IgGs. The results indicated that maximal tumor accretion of the radiolabeled antibody and normal IgG occurred within 1-3 days, with a marked selective accretion of antibody in the tumor being evidenced at 3-7 days because of clearance of normal IgG. Radioactivity derived from antibody IgG showed 6.5 to 118.7 times that found in other tissues, as measured by videodensitometry, whereas organ radioactivity counting revealed ratios of only 6.7 to 29.6. Specificity of tumor-cell accretion of the radiolabeled antibody was confirmed by microscopic autoradiography, showing intense labeling of the proliferating perimeters of GW-39 tumors. WBAR was found to have a resolution of 0.10 to 0.25 mm in 100-g hamsters, which appears to be greater than the resolving power of external body imaging by gamma camera scintigraphy. These studies suggest the use of WBAR and microautoradiography to complement external imaging methods for the analysis of antibody distribution and localization in cancer radioimmunodetection models.

Animals↗

Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement.

Severe hypertension causes global and regional changes in myocardial perfusion and substrate utilization. Regional perfusion and fatty acid utilization were evaluated by dual-tracer autoradiography in normotensive and hypertensive rats of the Dahl strain. The regional distributions of perfusion and fatty acid utilization were homogeneous in normotensive rats. Severe hypertension was associated with a homogeneous pattern of regional perfusion, but fatty acid utilization was focally decreased in the free wall of the left ventricle. The decrease in fatty acid uptake was associated with a concomitant increase in glucose utilization. These findings suggest that severe hypertension is associated with uniform myocardial perfusion and focal alterations in the substrates used for the performance of myocardial work.

Animals↗

A mucocele of the submandibular gland.

We encountered an unusual case of a mucocele arising from the submandibular gland. Among the limited number of cystic salivary gland neoplasms reported in the literature, there have been no reports, to our knowledge, of a similar cystic lesion. The unique characteristics of this mass permitted definitive diagnosis by computed tomographic scanning.

Adenolymphoma↗

The development and in-vivo behavior of tin containing radiopharmaceuticals--I. Chemistry, preparation, and biodistribution in small animals.

Tin is an essential ingredient of most technetium-99m radiopharmaceutical preparations but its in-vivo distribution and long-term fate are not well understood. Tin-117m (t1/2 14d; gamma 159 keV, 86%) is an ideal tracer for studying biological behavior of tin compounds as well as for developing clinically-useful radiopharmaceuticals. This work describes the preparation and in-vivo distribution in mice of a number of tin-117m labeled compounds with commonly used ligands. High bone uptake of most compounds studied as well as the unexpectedly high bone uptake of Sn4+-DTPA indicates a high bone affinity of tin bound to chemically diverse ligands. Various compounds show subtle but significant differences in blood clearance, excretion, and soft-tissue uptake. Differences among Sn2+ and Sn4+ compounds with the same ligand are particularly noteworthy. For stannic chelates, higher bone uptake, faster blood clearance, and reduced soft-tissue concentration were observed. It appears that tin compounds bind to bone predominantly through the tin atom and that the differences in biodistribution depend on factors such as the net charge on the complex, the oxidation state of tin, and hydrolytic and kinetic stabilities of the complexes. The results indicate that the favorable half-life and decay characteristics of tin-117m in various stannic compounds, especially stannic-DTPA, make it potentially useful as an agent for skeletal scintigraphy and radiotherapy of bone tumors.

Animals↗

The development and in-vivo behavior of tin containing radiopharmaceuticals--II. Autoradiographic and scintigraphic studies in normal animals and in animal models of bone disease.

Various 117mSn (2+ and 4+) compounds in well defined oxidation states were studied in normal mice using whole body autoradiography (WBARG), tissue distribution and scintigraphy in animal models of vitamin A induced bone disease, fracture, infected fracture and ischemic muscle lesions. The 117mSn4+-DTPA showed high affinity to normal bone with low soft tissue concentration. Increased deposition of this compound in fractures and ischemic lesions in muscle was also demonstrated. In hypervitaminosis A, reduced bone uptake of 117mSn4+-DTPA was shown to occur. Nude mice bearing osteogenic sarcoma of human origin showed uptake in spiculated pattern. The similar distribution of 117mSn4+-DTPA which does not contain phosphate or phosphonate groups, and the 99mTc(Sn) skeletal imaging compounds may indicate that tin is important in binding to bone. 117mSn4+-DTPA may not be ideal for routine imaging except when long term follow up is required. It should however be considered for therapy of bone tumors because of the long physical half-life of 117mSn (t1/2 = 14.03 days), abundance of short-range conversion and Auger electrons and its preferential deposition in cortical bone as indicated by our results.

Animals↗

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↗

Prevalence and clinical associations of intraocular pressure changes in Graves' disease.

We investigated an unselected series of 55 patients with treated or untreated hyperthyroid Graves' disease, assessing their clinical and laboratory status and ophthalmological findings, including the difference in intraocular pressure (dIOP) between upgaze and straight gaze using applanation tonometry. An increased dIOP (greater than 2 mm Hg) was detected in only 22% of Graves' patients [who had a mean dIOP of 3.5 +/- 1.6 (+/- SEM) mm Hg]. dIOP did not correlate with age, sex, age at disease onset, duration of disease, mode of antithyroid treatment, or thyroid function testing at the time of examination. Mean Hertel exophthalmometry measurements in patients with a dIOP greater than 2 mm Hg were 22.0 +/- 2.9 mm compared with 18.4 +/- 3.7 mm in those with a dIOP less than 2 mm Hg (P less than 0.027, by Wilcoxon rank sum test). Only 58% of patients with increased dIOP had clinical exophthalmos, but all had other evidence of Graves' eye disease. Computed tomographic scanning revealed significant proptosis and/or orbital muscle involvement in all of the patients with increased dIOP.

Adult↗

Pancreas accumulation of radioiodinated HIPDM in mice and rats.

High pancreatic affinity for 131I-labeled HIPDM was observed in mice and rats. Although the brain uptake of [131I]HIPDM is very fast, the pancreatic uptake is rather slow. The pancreas to liver ratios (per gram) were 5.08 +/- 0.52 in mice and 5.15 +/- 0.65 in rats at 2 hr and 7.05 +/- 0.53 in mice and 8.06 +/- 1.14 in rats at 5 hr after administration. These ratios are higher than those obtained with routinely used pancreatic agent [75Se]selenomethionine. An increase in liver uptake and decrease in pancreatic uptake was observed at higher dose of carrier HIPDM, which resulted in lower pancreas to liver ratios. HIPDM is a new type of compound which shows predilection for pancreas. Our results suggest that [123I]HIPDM might be a useful agent for pancreas imaging.

Animals↗

Acute response to elastase in sheep lungs measured with Ga-67.

The early inflammatory changes in sheep's lungs were studied with Ga-67 citrate, injected i.v. immediately following intrabronchial instillation of different doses of elastase into the right diaphragmatic lobes of 15 sheep. The elastase-induced lesions in the first five sheep (two received 4,000 units; three got 6,000) were imaged up to seven times in an 8-day period to measure the temporal changes in the lesion and to select the appropriate imaging time; the other ten sheep (800-8,000 units) were imaged once at 52 hr. Localization of Ga-67, as seen on the posterior and right lateral projections, was confined to a well-circumscribed region in the right lung field. The lesion could be detected as early as 4 hr after elastase instillation. It decreased to 60% of its initial area at 4 hr, while the total Ga-67 activity in the sheep remained constant after 52-75 hr. Gallium-67 uptake in the lesion correlated positively with the dose of elastase (r = 0.88, p less than 0.001) and with the reduction in perfusion, as determined 4 wk after the elastase instillation (r = 0.66, p less than 0.05). Early Ga-67 uptake in inflammatory lung lesions could therefore be used as a reliable predictor of the size of the acute elastase-induced inflammatory reaction, as well as of the sequelae involving the regional vascular supply 4 wk later.

Animals↗