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C Sawas-Dimopoulou

Publications and source records attributed to C Sawas-Dimopoulou.

14 recordsLinked to original sources

Early detection of amphotericin B induced nephrotoxicity by 99mTc-DTPA: a useful test.

Amphotericin B (AMB) with a broad spectrum of antifungal activity is used for the treatment of life-threatening mycoses, especially in immunocomprised patients. Since measurements of the blood level of AMB and of creatinine do not provide early warning of AMB induced renal toxicity, we studied the effects of AMB on biodistribution of a glomerular agent, 99mTc-DTPA. In Swiss mice, the toxicity of AMB was studied at single intravenous doses of 0.5-3.5 mg/kg body weight. Dose dependent effects consisted of decreased blood clearance and urinary excretion. Recovery of function was shown in dose ranges corresponding to high level clinical schedules. Serum creatinine changes lagged behind the 99mTc-DTPA alterations. This suggests that AMB toxicity might be monitored by blood/urinary clearance of 99mTc-DTPA.

Amphotericin B

Preparation and biological characteristics of 99mTc-diol a renal agent.

The present work concerns the production of 1,2-dihydroxypropyl-1-phosphonic acid (diol) by acid hydrolysis of (-cis) 1,2-epoxypropylphosphonic acid (phosphomycin), and its formulation as a kit easily labeled with [99mTc]pertechnetate. Biodistribution studies and whole-body autoradiographies in mice show that 99mTc-diol has a specific affinity for the kidneys: it is rapidly cleared from the blood and excreted in urine (12.09 +/- 6.40% ID are excreted in urine at 5 min and 70.81 +/- 2.41% ID at 30 min post-injection). Part of the injected activity remains in the kidney cortex sufficiently long to permit kidney imaging (5.66 +/- 0.91% ID is still in kidneys 1 h post-injection). In comparison with other agents which also localize in the kidney cortex, such as 99mTc-DMSA and 99mTc-glucoheptonate (99mTc-GHA), the main differences are the following: the peak of renal activity is reached early in the 5 min post-injection period for 99mTc-diol, only at about 10 min post-injection for 99mTc-GHA and after 3 h post-injection for 99mTc-DMSA. The uptake of 99mTc-diol by other organs, especially by bones, is much smaller than in the case of 99mTc-DMSA (1.25 +/- 0.11% ID of 99mTc-diol compared to 11.31 +/- 1.17% ID of 99mTc-DMSA, 1 h post-injection). Unlike 99mTc-DMSA, the biodistribution of 99mTc-diol is not significantly influenced by acid-base imbalance, in addition, its renal uptake decreases in the presence of probenecid whereas its urinary excretion increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Imbalance

Complexes of technetium-99m with phosphomycin, obtained by pH shifting: biological characteristics, whole-body autoradiography, gamma-camera study.

Phosphomycin (phos), a large spectrum antibiotic with preferential localization into the kidneys, can be labeled with technetium-99m at various pHs. However, the final pH in the labeling of phos by [99mTc]pertechnetate in the presence of SnCl2 seems to play a significant role in determining the biological properties of the final labeled product. Radiopharmacological characteristics of various forms of 99mTc-phos obtained at pHs 6.8, 4.5 and 2.5 were studied in mice, rats and rabbits. Significant differences in these products were shown by biodistribution studies in Balb/C mice and Wistar rats and confirmed by whole-body autoradiographies in mice and gamma-camera studies in rats and rabbits. 99mTc-phos, pH 6.8, has a high uptake in kidneys from 2 min after injection (10.25 +/- 1.11 %ID) to 3 h after injection (8.26 +/- 0.42 %ID) and a rapid urinary excretion (19.9 +/- 7.35 %ID at 2 min after injection and 75.11 +/- 3.48 %ID at 3 h). Intrarenal pharmacokinetics studied by autoradiography showed a high concentration in the inner medulla and pelvis at 1 min after injection followed by an increased localization in kidney cortex, like 99mTc-DMSA. Preferential uptake in bones was shown by 99mTc-phos, pH 2.5, from 5 min to 3 h after injection (15.05 +/- 2.67 %ID at 3 h compared to 1.79 +/- 0.19 %ID of 99mTc-phos, pH 6.8, at the same time). A high urinary excretion of 99mTc-phos, pH 2.5, is shown as in the case of other bone agents (76.5 +/- 3.46 %ID at 3 h post-injection) but without any kidney retention (1.80 +/- 0.26 %ID in kidneys 3 h post-injection).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Tissue localization of [125I]triiodothyronine in the periorbital area of mice: a microautoradiographic study.

A significant retention of [125I]triiodothyronine ([125I]T3) in the retrobulbar orbital area of mice has been previously shown. The present study was initiated to determine tissue and intracellular localization of the thyroid hormone in the above area which is concerned in human Graves' disease of the thyroid. Male and female Balb C mice were intravenously injected with 0.1 mL of [125I]T3 (0.2 mCi/micrograms). At various time intervals (30 s-10 min) the animals were sacrificed, bled and periorbital tissues were isolated under a dissecting microscope. Three series of samples were prepared: (a) frozen samples for cryomicrotome sections, (b) samples fixed in 10% formaldehyde for paraffin embedded tissues and (c) samples fixed in paraformaldehyde (2%), glutaraldehyde (2%) and 0.1 M sodium cacodylate for embedding in Epon-Araldite-DDSA. Sections 5 microns and 400-600 A thick for light and electron microscopy, respectively, were coated with Ilford L4 emulsion and exposed for 9-21 days. Light microscope autoradiography demonstrated that [125I]T3 injected intravenously is rapidly transported in the cells of fat tissue of the peribulbar orbital area and tissues with glandular or muscular function: the hormone showed a high affinity for the intra- and extraorbital lacrymal gland cells, the cells of the Harder's gland, those of the sebaceous and meibomian glands of the eye-lids, as well as for local muscular structures. Electron microscope autoradiography showed that radioactivity is already localized inside the cells 30 s after the i.v. injection of [125I]T3 and it is distributed throughout the cytoplasm, with a higher concentration in the vesicles of the Harder's gland cells (rich in lipids and porphyrin), in the endoplasmic reticulum and the mitochondria of the lacrymal glands. 10 min after injection, a shifting of the radioactivity towards the nucleus area was observed. In conclusion, after in vivo injection, the thyroid hormone rapidly penetrates the cells of fat glandular and muscular tissues in the orbital area. Intracellularly, the affinity of the hormone for the secretory vesicles, rough endoplasmic reticulum, mitochondria and nucleus suggest that T3 could play a role in secretory and metabolic functions of the tissues in the retrobulbar orbital area.

Animals

Alterations of the [59Fe]ferric citrate biodistribution in hyperferremic mice after the administration of pyrophosphate and desferrioxamine.

One of the most efficient anions in enhancing the ability of desferrioxamine (DFO) to remove iron from transferrin in vitro has been shown to be pyrophosphate (PYP). To evaluate the in vivo effect of PYP in hyperferremic mice, the biodistribution of [59Fe]ferric citrate was studied after the i.p. administration of: 1) only saline in the control animals; 2) an aqueous solution of tetrasodium diphosphate (PYP; 40 gm/2 g of b.wt.); 3) desferral (DFO; 12 mg/20 g of b.wt.); and 4) PYP + DFO at the respective dosages shown above. The radioactivity in each organ, blood, urine and feces was measured and referred to as percentage of the injected dose. PYP administered alone acted as a weaker chelator of iron than DFO. The combined administration of DFO and PYP contributed more than DFO or PYP separately, to the increase of urinary excretion of 59Fe and to the significant decrease of the radioiron concentration in liver (.01 less than P less than .05). The above induced changes are not, however, the additive result of the separate effect of DFO and PYP. That observation would suggest that DFO + PYP combined in a unique treatment, interact with iron through a common reaction pathway and that PYP plays in vivo a synergistic role in that interaction. The kind of iron with which DFO + PYP interacts is then suggested to be the transferrin-bound iron located in extracellular spaces of tissues.

Animals

99MTc-HIDA, a gallbladder imaging agent: experimental aspects.

The molecule N-(2,6-dimethyl-phenyl-carbamoyl-methyl)-iminodiacetic acid (HIDA), capable of chelating reduced 99mTc, was synthesized, characterized, labeled with 99mTc, and studied in experimental animals. The results indicated that the new 99mTc-radiopharmaceutical is rapidly cleared from the blood to the liver, then rapidly removed to the gallbladder and excreted into the duodenum through the common bile duct. A comparative kinetic study of 99mTc-HIDA and 131I-Rose Bengal performed in rabbits demonstrated that both radiopharmaceuticals had a similar blood clearance rate, but cleared at a different rate from liver to gallbladder. 99mTc-HIDA showed a faster accumulation in the gallbladder than 131I-Rose Bengal. These findings, combined with the advantage of the low acute toxicity of HIDA, were promising enough to encourage a further evaluation and clinical investigation of this new Tc-99m hepatobiliary agent.

Animals

57Co-bleomycin imaging study of tumors of the head and neck.

57Co-Bleomycin (57Co-BLM) was used to visualize malignancies of the head and neck because it does not present the disadvantages of many other radiopharmaceuticals. In a series of 21 patients with 9 control subjects and 12 cases of tumors. 57Co-BLM showed a high and rapid uptake in primary site and metastases of malignant tumors of various histologic types, but not in benign tumors such as angiofibromas. Compared to 67Ga-citrate. 57Co-BLM has many advantages for tumor imaging in the areas of nose, pharynx and larynx: No background activity due to the concentration of 57Co-BLM in normal structures of the head and neck has ever been observed, as opposed to what happens with 67Ga-citrate. Furthermore, the blood clearance of 57Co-BLM is much more rapid than that of 67Ga-citrate, so that an early study may be performed in a 6-24 hr. interval instead of 48-72 hr. with 67Ga-citrate. 57Co-BLM scintigraphy is an easy, non-invasive and sensible diagnostic technique in determining the extent of malignant tumors in ORL patients.

Bleomycin

[Comparative effectiveness of pulmonary scintigraphy and radiography in detecting toxic side-effects of Bleomycin treatment (author's transl)].

Pulmonary toxic effects subsequent to intravenous injections of bleomycin in cancer therapy have well been demonstrated. In order to prevent the acute pathological pulmonary manifestations of the treatment, it is necessary that the patient be submitted to repeated controls of the lungs. As yet, the efficiency of the current diagnostic procedures for detecting the lesions dues to bleomycin injections is not clearly demonstrated. The authors present the results of a comparative study on the effectiveness of radiological and scintigraphic examination of the lung in detecting toxic side-effects of bleomycin. Both procedures were used repeatedly on rabbits, before, during and after the bleomycin treatment. The findings are discussed on the basis of the macroscopic and histological examination of the lungs. The results demonstrate that pulmonary scintigraphy with radioactive macroaggregates is more sensitive than radiography in detecting the early lesions of the lungs after bleomycin treatment.

Animals