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Biomedical subjects

G Subramanian

Publications and source records attributed to G Subramanian.

At least 55 records · Page 3Linked to original sources
PubMed1986

Detection of diffuse glomerular lesions in rats: II. Comparison of indium-111 cationic small macromolecules with technetium-99m DTPA.

Dextrans with average molecular weights of 5,000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls. However, there was poor correlation between the early renal uptake of these agents and the clearance of simultaneously injected [99mTc]DTPA. The 2-hr organ distribution and urinary excretion of these agents were compared with the corresponding values of DTPA. The differences in clearance between rats with glomerular damage and controls were greater with aminated dextran (mol wt 5,000) than with DTPA, confirming previous work with infusions of nonradioactive charged dextrans and neutral inulin. The cationic dextrans appear to reflect the presence or absence of the normal anionic charge of the glomerular membrane as well as changes in filtration rate. Aminated inulin did not differentiate between controls and rats with glomerular disease any better than DTPA, probably because the number of amino groups conjugated was insufficient to produce the charge effect.

Animals↗
PubMed1986

Detection of diffuse glomerular lesions in rats: I. Comparisons of conventional radioactive agents.

Conventional renal diagnostic agents, [131I]hippuran, [99mTc]glucoheptonate (GHA), and [99mTc] dimercaptosuccinate (DMS) were compared with [99mTc] or [111In] diethylenetriaminepentaacetic (DTPA) for the detection of glomerular damage in rats compared with controls. The glomerular lesions were induced by the i.v. injection of puromycin aminonucleoside (PA) 9 days before the radionuclide studies, a model of spontaneous "minimal change" glomerulonephritis in humans. Computer-generated early renal uptake of [99mTc]DTPA or GHA correlated with the glomerular filtration rate (GFR) quantitated by biexponential plasma clearance of DTPA administered by single i.v. injection. The early renal uptake of hippuran and DMS correlated poorly with GFR as assessed by DTPA clearance. However, the 2-hr renal retention of DMS correlated well with the DTPA clearance. None of the parameters measured with [131I]hippuran correlated well with DTPA clearance, probably because of decreased protein plasma binding of hippuran secondary to hypoproteinemia in this experimental model. It was concluded that none of these agents was superior to labeled DTPA for the detection of glomerular damage in this experimental model.

Animals↗
PubMed1985

Radioimmunoimaging of venous thrombi using iodine-131 monoclonal antibody.

Murine monoclonal antibody (Mab) specific for the NH2-terminal region of human fibrin, but not cross-reactive with fibrinogen, was used in radioimmuno-imaging of fresh, induced venous thrombi in three dogs. Iodine-131-labeled Mab was injected intravenously, with iodine 125-labeled polyclonal murine gamma-G globulin (IgG) simultaneously injected as a control. Images were strongly positive at 24 and 48 hours in all three animals, with thrombus-to-blood and thrombus-to-muscle ratios of 8.4 and 228.0, respectively, for I-131-labeled Mab; these ratios for control IgG were 1.2 and 13.0. Radioimmunodetection of thrombi in vivo is feasible in dogs and may have clinical application since Mab is specific to human fibrin.

Animals↗
PubMed1985

Technetium-99m DADS complexes as renal function and imaging agents: II. Biological comparison with iodine-131 hippuran.

To find a 99mTc agent with a high renal extraction efficiency similar to [131]hippuran, 21 analogs of DADS were labeled and evaluated. Preliminary screening by serial gamma camera imaging in rabbits showed that most analogs had a higher liver uptake and/or slower renal clearance, than hippuran. Three agents (P-DADS, AP-DADS, and CAP-DADS), exhibiting a relatively rapid blood clearance and lower liver uptake in the rabbit, were studied in greater detail in comparison with hippuran and CO2-DADS-A, the best analog to date. In the rat, the plasma clearance of the four DADS analogs was slower than that of hippuran. In rats with tubular damage induced by cisplatin, the difference in renal retention at 1 hr compared to controls was much greater with hippuran than with the DADS compounds. In the dog, there was marked hepatic retention of the four DADS compounds. In volunteers, serial posterior images obtained with these [99mTc]DADS complexes showed significant hepatic as well as renal activity. The 1-hr plasma clearance and urinary excretion were much lower than with simultaneously injected hippuran. Although these 99mTc agents are satisfactory for imaging the kidneys, they closely mimic the biodistribution of hippuran only in the rabbit, and not in the rat, dog, or man.

Animals↗
PubMed1984

Technique of leukocyte harvesting and labeling: problems and perspectives.

Mixed leukocyte suspensions obtained after gravity sedimentation of red cells and labeled with 111In lipophilic chelates are now widely used clinically for abscess localization at many medical centers. So far, labeling with 111In-oxine or tropolone has been more successful than any 99mTc method. More sophisticated approaches are available for isolation and labeling of specific leukocyte cell types, to study their migration in vivo. The most significant advances in cell harvesting include newer density gradients for isopyknic centrifugation (nonionic contrast media such as Nycodenz and Percoll, PVP-coated colloidal silica), centrifugal elutriation, and flow cytometry. Unlike current radioactive agents which label many cell types indiscriminately, more selective ligands are being developed which bind to specific cell surface receptors. These will label certain leukocyte populations or subtypes while not reacting with others, thereby avoiding laborious separation techniques. Monoclonal antibodies against leukocyte cell-surface antigens appear particularly promising as agents for selective cell labeling.

Abscess↗
PubMed1984

N,N'-bis(S-benzoylmercaptoacetamido) ethylenediamine and propylenediamine ligands as renal function imaging agents. I. Alternate synthetic methods.

A new method was developed to synthesize tetradentate ligands containing the N,N'-bis(S- benzoylmercaptoacetyl ) ethylenediamine and propylenediamine moieties (DADS compounds). Methods are also represented with which to synthesize some of the positional isomers of the above compounds. These isomers represent a new class of compounds. A total of 21 different compounds were prepared. These will be used in an effort to establish a relationship between structure and renal imaging properties.

Alanine↗
PubMed1983

New diphosphonate compounds for skeletal imaging: comparison with methylene diphosphonate.

Three-hour biodistribution of Tc-99m complexes of six diphosphonates was compared in rabbits with tibial lesions to determine which was best for detection of focal bone lesions. Sr-85 was used as a standard. N,N-dimethylaminomethylene diphosphonate (DMAD) was the only agent with a higher lesion/normal bone ratio than methylene diphosphonate (MDP), attributable to lower concentration in normal bone. Hydroxymethane diphosphonate (HDP) and 2,3-dicarboxypropane-1, 1-diphosphonate (DPD) demonstrated higher concentration than MDP in normal bone without improving lesion contrast. They also exhibited much higher uptake in the liver and kidney, as well as muscle and red marrow in the case of DPD. None was superior to MDP as an all-purpose skeletal agent, though others may be better for specific applications.

Animals↗
PubMed1982

A new formulation of Tc-99m minimicroaggregated albumin for marrow imaging: comparison with other colloids, In-111 and Fe-59.

The biodistributions of five Tc-99m colloids were compared with the 24-hr distributions of Fe-59 and In-111 in dogs by direct radioassay 1 hr after intravenous injection. One formulation of Tc-99m minmicroaggregated albumin (particle size 30-100 mn), produced the highest marrow concentration, approximately six times that of Tc-99m sulfur colloid, with similar blood, and liver concentrations and a lower splenic uptake. Nevertheless, the best colloid marrow uptake was lower than the 24-hr value for In-11 and much lower than that for Fe-59. The marrow concentration of minimicroaggregated albumin was also higher than that of sulfur colloid in rats at 30 min after injection. The principal disadvantage of Tc-99m antimony sulfide colloid was its slow blood clearance. Clinical evaluation of Tc-99m minimicroaggregated albumin for marrow imaging appears warranted, although its hepatic activity will obscure overlying and immediately adjacent marrow.

Animals↗
PubMed1981

Detection of experimentally produced acute pulmonary arterial occlusion by methyl iodide-131 inhalation imaging.

Methyl iodide-131 (CH3I-131) is described as an agent for detection of acute experimentally produced pulmonary arterial occlusion in dogs. When gaseous CH3I-131 is inhaled, radioactivity passes instantaneously from the alveoli to the lung capillary bed. Where pulmonary blood flow exists, activity is washed out into the systemic circulation, but in areas of blood stasis, a transient pulmonary "hot spot" remains. CH3I-131 is easily produced and inexpensive, but administration is awkward and strict radiation safety precautions are mandatory.

Animals↗
PubMed1981

Comparison of renal extraction efficiencies for radioactive agents in the normal dog.

The renal extraction efficiencies for various radioactive agents were measured in normal anesthetized dogs during 1 hr after a single intravenous injection. Radioassays were made on serial blood samples drawn simultaneously from the aorta upstream from the renal arteries and from one renal vein. As a reference substance [131I]o-iodohippurate was injected concurrently in all experiments. Blood clearances from serial venous samples and urinary excretion also were measured. Extraction efficiency from whole blood was calculated as (A-V) divided by A, where A = aortic concentration and V = renal venous concentration. This ratio for commercial [131I]o-iodohippurate fell steadily from 88% at 30 sec to 50% at 1 hr. For "purified" [131I]o-iodohippurate the fall was less marked, to 61% at 1 hr. The EE ratios for all other agents were stable after the first minute. The Tc-99m complexes of DTPA, glucoheptonate, and acetylcysteine had ratios averaging 27-29%. The ratios of Tc-99m DMS and Hg-197 chlormerodrin had much lower average values of 8 and 14%, respectively. None of the newer agents approached the extraction efficiency of [131I]o-iodohippurate.

Animals↗
PubMed1980

Simultaneous 99mTc-P-butyl-IDA and 131I-rose bengal scintigraphy in neonatal jaundice.

Eight neonates with jaundice were studied simultaneously with 99mTc-p-butyl-IDA and 131I-rose bengal. Due to physical decay, 99mTc-p-butyl-IDA failed to demonstrate delayed excretion through the patent extrahepatic biliary tract in 3 of 5 patients with concomitant hepatitis; 131I-rose bengal showed small-bowel activity in all 5. Neither agent demonstrated small-bowel activity in 3 neonates with extrahepatic biliary atresia. Based on this clinical trial, 131I-rose bengal remains the radiopharmaceutical of choice for distinguishing between hepatitis and biliary atresia in these patients.

Animals↗
PubMed1980

Distribution of leukocytes labeled with In-111 oxine in dogs with acute inflammatory lesions.

The biodistributions of In-111 oxine (with and without leukocyte labeling) of Ga-67 citrate and of In-111 chloride were compared in 30 dogs with chemical and bacterial abscesses and acute joint inflammation. Serial blood samples were taken and tissues radioassayed at 24 hr. The concentration of In-111-oxine leukocytes in all three types of inflammatory lesion was invariably much higher than that of Ga-67 injected simultaneously. For bacterial abscesses, the mean abscess-to-muscle concentration ratio was 3,000 for labeled leukocytes and 72 for Ga-67. Aqueous buffered In-111 oxine sulfate solution appeared better for labeling leukocytes than In-111 oxine in ethanol. When In-111 oxine was not incubated with leukocytes before injection, or if the cells were poorly labeled or damaged, the abscess localization was often inferior to that of gallium. Localization of In-111 chloride also appeared inferior to that of gallium. No significant difference in distribution in the major organs or inflammatory lesions was demonstrable between labeled suspensions of "pure"neutrophils harvested by elutriation and "mixed"cell suspensions of leukocytes after erythrocyte sedimentation with hydroxyethyl starch. For both types of leukocyte suspension labeled with In-111 oxine, the average recovery of cell-bound activity in the circulating blood at 4 hr was 32% of the administered activity, inferior to that of DFP-32. It is concluded, therefore, that In-111 oxine is a more effective agent than Ga-67 for the detection of acute focal inflammatory lesions if leukocytes are properly labeled, but current techniques are unsatisfactory for the study of neutrophil kinetics.

Abscess↗
PubMed1978

Labeling of platelets with oxine complexes of Tc-99m and In-111. Part 1. In vitro studies and survival in the rabbit.

We have used both Tc-99m oxine and In-111 oxine to study the effects in the rabbit of various parameters on platelet labeling and the in vivo survival of platelets harvested by four different methods. For In-111 oxine, platelet labeling in saline produces much higher efficiencies (90%) than labeling in the presence of plasma (20%), with no significant shortening of in vivo survival (1% survival at 5.9 days). For Tc-99m oxine, labeling efficiencies are considerably lower (30%) and survival is shorter (1% survival at 3.8 days). For both radioagents, a 30-min labeling incubation at room temperature is suggested.

Animals↗
PubMed1978

Platelets labeled with oxine complexes of Tc-99m and In-111. Part 2. Localization of experimentally induced vascular lesions.

Using rabbit platelets harvested and labeled with either Tc-99m or In-111 oxine as described in Part 1, we have successfully imaged experimentally induced fresh venous thrombi and newly injured arterial intima. Visualization of lesions up to 6 hr old is striking. Thrombi and arterial damage 24 hr old, however, were usually not imaged successfully; nor were preformed platelet-poor arterial emboli. The varying rates of platelet deposition in vascular lesions of different ages and types account for these observations. Should human cells prove as effective, widespread clinical application is anticipated.

Animals↗
PubMed1977

Myocardial uptake (rabbit) of six 99mTc-tagged pharmaceuticals and 85Sr after vasopressin-induced necrosis.

A new rapid method for producing myocardial necrosis in rabbits was developed, using percutaneous intramyocardial injection of vasopressin in peanut oil. The 15-min procedure resulted in a mortality rate of 15% and a success rate among surviving animals of 50%. When the lesions were 24 hr old, strontium-85 and a technetium-99m-tagged agent were injected intravenously simultaneously, and the animals were killed 1,6, and 24 hr later for tissue radioassay. Strontium-85 failed to accumulate appreciably in the lesions. Three bone-seeking technetium complexes (pyrophosphate, methylene diphosphonate, and imidodiphosphonate) produced lesion-to-normal myocardial ratios of 6,5, and 14, respectively, at 1 hr, and 20,30, and 33 at 6 hr. The ratios for 99mTc-glucoheptonate were only 2 at 1 hr and 4 at 6 hr, while the ratios of 99mTc-acetylcysteine and 99mTc-citrate were even lower.

Animals↗