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Biomedical subjects

J Weininger

Publications and source records attributed to J Weininger.

At least 19 recordsLinked to original sources

Influence of pH adjustment agents on the biologic behavior of osmium-191 impurity in iridium-191m generator eluates.

The influence of four pH adjustment agents on the biologic behavior of osmium-191 (191Os) impurity in 191Os/191mIr generator eluates was studied. Extended body clearance and biodistribution studies were performed in mice. The solutions to be injected were obtained by eluting generators with a 0.9% NaCl solution at pH 1. The pH of these eluates was adjusted to 5-9 with succinate, phosphate, lysine or NaOH solution. Our results demonstrate that the biologic behavior of these generator eluates is significantly dependent on the agent used for pH adjustment. Buffering with lysine leads to the best results: (a) the mice show no adverse reaction after injection of 150 human doses and the body clearance is very rapid and (b) more than 75% I.D. at 24 hr postinjection. Preliminary calculations based on these results suggest a significant decrease in the estimated patient radiation dose when lysine buffered 191Os/191mIr generator eluates are used for radionuclide angiography.

Animals

Clot uptake of labeled active and inhibited tissue plasminogen activator.

The clot uptake of labeled active and inhibited t-PA was compared. The most efficient inhibition was obtained with diisopropyl fluorophosphate (DFP) after 4 h incubation at room temperature. Enzyme activity was followed by fibrin-plate assay, radioactivity-release technique and proton magnetic resonance (PMR). The novel PMR method developed by us is sensitive to the effect of as low as nanogram amounts of t-PA on the interaction between the fibrin and the compartmentalized water trapped in the clot. Binding of labeled enzyme to fibrin-coated plates showed that the deactivation by DFP did not impair the affinity of t-PA for fibrin. A rapid binding of 125I-labeled t-PA to the clot occurred, which reached a maximum in 30 min and declined with time. This pattern was explained by consecutive clot binding and lysis. The binding of DFP-t-PA to the clot differed markedly from that of the active protein; 2 h post-incubation the uptake of DFP-t-PA was more than double that of the untreated t-PA. Parallel measurements in clots prepared from human blood showed a qualitatively similar trend. The biodistribution of radiolabeled t-PA in mice was similar for the active and inhibited forms. Blood activity reached 10% of the injected dose within 10 min. DFP-t-PA may prove to be a useful reagent for in-vivo localization of thrombi.

Animals

Osmium-191/iridium-191m generator based on silica gel impregnated with tridodecylmethylammonium chloride.

A new separation system for an 191Os/191mIr generator is described. The system is composed of two columns in a series: a main column, packed with silica gel impregnated with tridodecylmethylammonium chloride (loaded with high activity 191Os as an osmyl chloride); and a scavenger column, packed with activated charcoal. Iridium-191m is eluted from the generator by pH 1 saline. For clinical use the eluate is buffered by succinate solution before injection. This new system is characterized by high performance (approximately 25% 191mIr recovery with 5 X 10(-4)% 191Os breakthrough) and long shelf-life (3 wk). The buffered eluate is sterile, pyrogen-free, and nontoxic, and contains no 192Ir. It is suitable for first-pass radionuclide angiocardiography with a very low radiation dose to the patient.

Adult

Effect of selenite on the toxicity of cis-DDP in mice: estimation of trace elements.

A significant accumulation of copper, zinc, iron, rubidium and bromine, in addition to platinum, was observed in kidneys and liver of mice treated with cis-DDP. This observation suggests that the toxicity of cis-DDP is due to the overall accumulation of trace elements and not only to the expected high platinum levels. Sodium selenite administration prior to cis-DDP results in fast clearance of all these trace elements from kidneys and liver; control levels are reached within 6 days. This may explain the important reduction in cis-DDP toxicity following selenite administration. An X-ray fluorescence (XRF) facility was used for the evaluation of the trace elements.

Animals

Proton MR properties of lyophilized urine samples from normal and stone former individuals.

Proton MR measurements were performed in lyophilized urine samples collected from 5 normals (N) and 5 idiopathic hypercalciuric recurrent stone formers (SF). T1 and T2 relaxation times were measured with a Bruker PC Multispec at 20 MHz and 37 degrees C in the lyophilized samples and in samples gradually rehydrated. Significantly (p less than 0.01) prolonged T1 and T2 relaxation times were measured after addition of water to the lyophilized samples. The relaxation time prolongation patterns were significantly different (p less than 0.01) for the two groups; the rehydration curves of the lyophilized urine samples from the SF group had relatively shorter lag than that of N group. In calculations of water compartmentalization for similar water content, significant (p less than 0.01) differences in the fraction of bound water (FB) were found between the two groups. These results may reflect differences in the macromolecular properties, contents, in the amount of water binding sites and/or in the water multilayer thickness between the two groups. These differences, expressed as changes of the relaxation times values may provide new diagnostic possibilities of different renal pathologies.

Female

Hydration properties of urinary compounds obtained from normal and stone former individuals. An NMR study.

Proton magnetic resonance measurements were performed on lyophilized urine samples collected from 10 recurrent calcium oxalate stone former (SF) patients, 10 thiazide treated (TSF) patients and 14 normal (N) individuals. T1 and T2 relaxation times were measured with a Bruker PC Multispec at 20 MHz and 37C on the lyophilized sample and thereafter during gradual controlled rehydration. The prolongation of the relaxation times was found to be significantly different (p less than 0.001) for the SF and N groups, while it was similar for the SF and TSF groups. Water compartmentalization was then calculated according to the Fast Proton Infusion model. After the addition of similar amounts of water, significantly (p less than 0.01) different hydration fraction (HF) and fraction bound (FB) values were calculated for the N and SF groups, while similar values were obtained for the SF and TSF groups. The results reflect differences in the urinary contents and/or properties of N and SF groups. It seems that there are more hydrophilic compounds in the urine of N individuals than in that of SFs. It can be speculated that the urinary macromolecules of SFs differ from those of Ns in the amount of water binding sites and in the water multilayer thickness surrounding them. The present results point to possible pathogenic differences between SF and N individuals.

Adult

Labeling of sarcoma associated monoclonal antibody with 111In, 67Ga and 125I.

Labeling of human sarcoma-associated murine monoclonal antibody (MAb) 23H7 with 67Ga and 111In by the bifunctional ligand method is reported. 67Ga was chelated to the MAb via desferrioxamine B and 111In via the cyclic anhydride of DTPA. Higher specific activity was obtained with 67Ga (4-5 microCi/micrograms) as compared with 111In (2 microCi/micrograms). The binding capacity of the MAb was confirmed by repeated indirect immuno-fluorescence assays performed before and after labeling. A fast blood clearance was observed: 33% recovered dose (R.D.) blood level 3 h post-injection as compared with 56% after injection of control polyclonal IgG. Preliminary results on chemically induced sarcoma bearing mice showed a relatively high tumor uptake of the labeled antibody.

Animals

Proton magnetic resonance in experimental acute and chronic renal failure in rats.

Kidney cortical and medullary "spin-lattice" (T1) and "spin-spin" (T2) relaxation times were measured by spectroscopy in several types of experimental renal failure in rats. The T1 and the measured tissue water content were used to calculate the fraction bound (FB) and hydration fraction (HF) according to a fast proton diffusion model. The present study demonstrated the possibility to differentiate between normal and pathological renal tissue resulting from renal artery clamping (RAC), renal pedicle clamping (RPC) with or without reflow, glycerol-induced acute renal failure with or without previous dehydration, and chronic hypertensive renal failure induced by 5/6 nephrectomy and saline loading, with low (6%) or normal (21%) protein diet. Shortened T1 and prolonged T2 found in both cortex and medulla of the glycerol-induced ARF in dehydrated rats seem to represent a MR ischemic pattern. The prolongation of T1 and T2 and the increase in water content in the other groups seem to relate to different amounts of tubular obstruction and renal congestion. In summary, characteristic MR properties of different types of renal failure may provide etiological and pathogenetic diagnostic possibilities.

Acute Kidney Injury

Human sarcoma-associated murine monoclonal antibody labeled with indium-111, gallium-67, and iodine-125.

Monoclonal antibody (MAb) 23H7 is a hybridoma-derived IgG that is generated following fusion of mouse myeloma cell line P3U1 and spleen cells from BALB/c mice hyperimmunized with a human fibrosarcoma. It detects a mesenchymal antigen of 23KD expressed on human sarcoma tissues and other neoplasms, including myeloid leukemias, but it rarely binds to normal tissues. The MAb 23H7 was labeled with 67Ga and 111In using the bifunctional ligand method. The 67Ga was chelated to the MAb via desferrioxamine B, while 111In was chelated via the cyclic anhydride of diethylenetriamine pentaacetic acid. Higher specific activity was obtained with 67Ga than with 111In (4.5 and 2 muCi/microgram, respectively); both gave stable complexes. When 23H7 was labeled with 125I, considerable breakdown was observed. This, together with the physical shortcomings of this isotope, emphasizes the advantages of labeling with 111In and 67Ga. The rapid blood clearance of the labeled sarcoma-associated MAb may be beneficial for early tumor uptake and for imaging shortly after injection.

Animals

Proton MR study of different types of experimental acute renal failure in rats.

Kidney cortical and medullary spin-lattice (T1) and spin-spin (T2) relaxation times were measured in several types of experimental acute renal failure in rats with a Bruker PC "Multispec." Gentamicin ARF was obtained after one i.p. injection of 100mg Gentamicin/kg BW/day for 8 days. Glycerol ARF: 24 hours after one i.m. injection of 10 ml 50% Glycerol/kg BW. Obstruction ARF: 3 days after complete ureteral ligation. Renal tissue total water content, hydration fraction, fraction bound, blood urea and creatinine were measured at the end of the experiments. Shortened T1 and prolonged T2 were found in both cortex and medulla in the Glycerol ARF group. Gentamicin renal toxicity and the non-functioning kidney with ureteral obstruction are characterized by significant prolongation of T1 and T2 in cortex, while the medullary T1 and T2 were prolonged only in obstruction ARF. The highest T1 and T2 were found in the obstructed non-functioning kidney. The total water content decreased in the Glycerol ARF, increased in the obstruction and remain unchanged in Gentamicin ARF. The hydration fraction and the fraction bound changed significantly in the opposite direction with the total water content. Different profiles of renal cortical and medullary magnetic resonance properties found in several models of experimental ARF in rats indicate that MR properties may provide etiopathogenetic diagnostic possibilities.

Acute Kidney Injury

Technetium-99m-labeled red blood cell imaging.

Red blood cells labeled with 99mTc constitute a suitable intravascular agent for imaging of vascular abnormalities. Hemangiomas are characterized by low perfusion and a high blood pool. This "perfusion blood-pool mismatch," not encountered in other lesions, may help in the specific diagnosis of this tumor. This is particularly so in cavernous hemangiomas of the liver where three-phase 99mTc-labeled red blood cell scintigraphy should precede liver biopsy. Red cell scintigraphy also is useful for establishing the vascular nature of hemangiomas of the head and neck and the skin and for diagnosis of venous occlusion. Heat-damaged red blood cells provide a specific spleen imaging agent. This should be used when patients with suspected splenic pathology have equivocal colloid scintigraphy.

Adult

186Re-HEDP: a potential therapeutic bone agent.

A lyophilized kit preparation of HEDP for labelling with 186Re has been developed as a potential bone agent useful for both diagnosis and therapy. High pressure liquid chromatographic analysis showed that the 186Re-HEDP is a mixture of several components. Preliminary in vivo studies in several animal species showed that both the 186Re-HEDP mixture and the HPLC-purified main component are bone-seeking agents with slow blood and soft-tissue clearance rates. HPLC purification slightly improved the quality of the image. In mice and rats with trauma-induced osteogenetic activity in one leg, the bone uptake of the traumatized leg was 1.7-1.9 times higher than of the normal leg. The lesion-to-normal bone ratio was 4-5.4.

Animals

Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey.

Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.

Animals

Comparative cardiac effects of three hepatobiliary radiopharmacologicals in the dog: concise communication.

Three hepatobiliary agents with an acetanilide-imidoacetic-acid moiety resembling that in lidocaine were investigated for their possible effects on contractility and conductivity in the heart and on arterial pressure and aortic blood flow. This was done in the light of lidocaine's numerous cardiac side effects. HIDA, BIDA, and DIPA, each with traces of decayed Tc-99m, were injected i.v. into anesthetized dogs with an A-V block, and their effects on the above parameters were followed until control levels were reestablished. Whereas lidocaine raises the diastolic threshold and prolongs the refractory period, the three agents tested do not prolong myocardial conductivity. Both HIDA and BIDA have an effect similar to that of lidocaine, but DIPA has no effect on the latter two parameters. Moreover, whereas lidocaine depressed myocardial contractility, blood pressure, and blood flow, HIDA has a less prominent effect on these parameters, and neither BIDA nor DIPA has any such effect. It is concluded that even though the effect of HIDA on the heart is milder than that of lidocaine, the effects of both BIDA and DIPA are even less pronounced, and they are less likely to cause cardiac side effects when similar doses are administered during nuclear medicine procedures.

Animals