The efficacy of DFO-HOPO, DTPA-DX and DTPA for enhancing the excretion of plutonium and ameriicum from the rat.

A hydroxypridinone derivative of desferrioxamine (Na-DFO-HOPO), a dihydroxamic derivative of diethylenetriaminepenta-acetic acid (ZnNa-DTPA-DX), and DTPA (CaNa3- and ZnNa3-DTPA) were tested at dosages of 30 mumol kg-1 for their ability to remove 238Pu or 241Am from rats after their intravenous injection as citrate or inhalation as nitrate. The most effective treatment regimen for injected Pu was the repeated administration of DFO-HOPO; by 7 days the body content was reduced to 8% of that in untreated animals. Repeated dosages of 3 mumol kg-1 DFO-HOPO were as effective as those of 30 mumol kg-1 DTPA. After inhalation of Pu nitrate, repeated treatment with DTPA, DTPA-DX or DFO-HOPO reduced the body content by 7 days to, respectively, 10, 15 and 31% of those in untreated animals. After inhalation of Am, DTPA-DX and DTPA were equally effective, the body contents being reduced to 7% of control values with repeated treatment. Injection of DFO-HOPO was ineffective for enhancing the elimination of inhaled or injected Am. The results confirm the strategy of examining the use of siderophore analogues for the decorporation of Pu or Am. However, at present DTPA should remain the agent of choice, particularly after inhalation.     

The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.     

Dosimetry of several DTPA radiopharmaceuticals in cisternography.

Previously published biologic distribution and clearance data for 169Yb-DTPA in cisternography were utilized to obtain effective spinal segment clearance data for six other easily dhelated radionuclides: 99mTc, 113mIn, 111In, 67Ga, 51Cr, and 203Pb. Absorbed radiation doses to the spinal cord and nerve roots were calculated for each radioactive DTPA compound, employing appropriate cylindrical geometry and reduction coeffients for the dose contributions from the electrons of each radionuclide. Doses are maximal at the surface and decrease rapidly with distance from the surface. The relative useful photon flux from each DTPA radiopharmaceutical for approximately the same average absorbed radiation dose to the spinal cord was determined. The results indicate that 111In and 203Pb should be considered as possible radionuclide tags for DTPA cisternographic imaging.     

Comparison of the biodistribution of manganese-54 DTPA and gadolinium-153 DTPA in dogs

The biodistribution of [54Mn]DTPA and [153Gd]DTPA dimeglumine were investigated and compared following i.v. administration to fasting anesthetized dogs. Unlike most previously reported metal ion-DTPA complexes, [54Mn]DTPA showed high uptakes in several organs including the liver, bile, pancreas, bowel, and kidney. This uptake was independent of the pH of the injected solution. Accumulation in these organs suggests a potential role for [Mn]DTPA as a paramagnetic contrast agent for NMR imaging. With the exception of the kidneys, [153Gd]DTPA showed no evidence of tissue specific uptake over the course of 4 hr, consistent with it being an extracellular ion that is cleared by glomerular filtration.     

Comparison of the biodistribution of gadolinium-153 DTPA and technetium-99m DTPA in rats

Twenty-three mature Sprague-Dawley male and female rats were simultaneously injected with trace quantities of [153Gd]DTPA and [99mTc]DTPA and 0.5 mmol/kg of nonradioactive gadolinium DTPA. Rats were killed at 1 min, 5 min, 10 min, 15 min, and 30 min after the intracardiac bolus injection. The heart, lungs, liver, brain, kidney, and blood were excised and counted in a well-counter to determine the amount of the injected material in each organ and blood. In order for the percent of total injected activity to be determined, a technique was developed which allowed discrimination of the 140 keV gamma-ray of 99mTc from sum peaks of 153Gd when the latter is counted in a well-counter with 4 pi geometry. Although the distribution of the two DTPA compounds was qualitatively similar, statistical analysis indicated that the amount of 99mTc deposited in the lungs was higher than 153Gd (p = 0.03), the amount of 99mTc deposited in the kidneys was lower than 153Gd (p = 0.0004) and the amount of 99mTc in the blood was higher than 153Gd (p = 0.0022). This may be due to the greater binding of [99mTc]DTPA or its minor impurities to plasma proteins.     

High speed injection of radiographic contrast media induces severe particulate contamination

In a study of exogenous particulate contamination during angiography, the effect of injection speed of four kinds of radiographic contrast media (RCM) was investigated. The particle count (> or = 10 microns) in all RCM increased in a speed-dependent manner and the increase was especially dramatic at 3 ml s-1. The extent of increase in particulate matter was higher for ioxaglate than for the other three RCM. As particulate matter is unwanted and unnecessary, to prevent the harmful effects in patients much attention should be paid to various factors generating particulate matters, such as characteristics of RCM and plastic syringe.     

Improved measurement of the glomerular filtration rate from Tc-99m DTPA scintigraphy in patients following nephrectomy

Objective

We aimed to improve Tc-99m DTPA glomerular filtration rate (GFR) scintigraphy (Gates’ method) in a prospective study using Cr-51 EDTA GFR test as a gold standard.

Methods

Fifty-seven Tc-99m DTPA GFR scintigrams in 45 subjects (male/female?=?33:12, age?=?45.9?±?17.6 years, 14 healthy volunteers and 31 nephrectomised patients) were compared using Cr-51 EDTA GFR tests. Using the %renal uptake of Tc-99m DTPA and Cr-51 EDTA GFR, a revised equation for GFR was established through linear regression analysis.

Results

The revised equation for improved GFR was GFR(mL/min)?=?(%renal uptake?×?11.7773)???0.7354. Gates’ original GFRs (70.1?±?20.5 mL/min/1.73 m²) were significantly lower than Cr-51 EDTA GFRs (97.0?±?31.9 mL/min/1.73 m²; P?<?0.0001), but the improved GFRs (98.0?±?26.3 mL/min/1.73 m²) were not different from (P?=?0.7360) and had a significant correlation with (r?=?0.73, P?<?0.0001) the Cr-51 EDTA GFRs. The revised GFR equation effectively demonstrated perioperative GFR changes in kidneys that were operated on and the contralateral kidneys at 3 and 6 months post-partial nephrectomy (n?=?25).

Conclusions

GFR measurement using Tc-99m DTPA scintigraphy could be significantly improved by a revised equation derived from the comparison with Cr-51 EDTA GFR.

Key Points

? Measurement of glomerular filtration rate is difficult following nephrectomy. ? Measurements can be significantly improved by new renal sctintigraphic methods. ? This helps physicians to measure kidney function of patients following nephrectomy. ? Management of renal tumour patients should become more effective.     

Examining the non-homologous repair process following cisplatin and radiation treatments

Purpose : To investigate the extent of non-homologous end-joining (NHEJ) in the mechanism of cisplatin radiosensitization. Materials and methods : Ku80-deficient cells are deficient in the non-homologous DNA double-strand break repair process, while the wild-type MEF cells maintain full mammalian cell repair capabilities. Both cell lines were exposed to clinically applicable doses of cisplatin (1, 3 and 6 μ g ml -1) for 1 h immediately before exposure to 250 kV X-rays. Radiation responses were plotted for each cell line and for all doses of cisplatin to observe relative levels of radiosensitization. Split-dose experiments were also performed on each cell line to measure levels of sublethal damage repair. Results : Radiosensitization was observed in the wild-type cells but not in the Ku80 cells when treated with a combination of 1 μ g ml -1 cisplatin followed by X-rays, implying that the NHEJ pathway may play a large role in cisplatin radiosensitization. Concurrent administration of this cisplatin dose with radiation produced similar levels of radiosensitization. Conversely, 3 and 6 μ g ml -1 cisplatin applied immediately before radiation revealed an increasing resistance to radiation in both cell lines -- possibly due to resistant subpopulations of cells remaining after subsequent lethal doses of cisplatin. Further experiments revealed that the high concentrations of cisplatin did not alter cell cycle distribution. Finally, split-dose experiments revealed that the NHEJ pathway also plays a significant role in sublethal damage repair. Conclusions : The study reveals that clinically applicable doses of cisplatin treatment results in the radiosensitization of mammalian cells due to the inhibition of the operation of NHEJ.     

Examining the non-homologous repair process following cisplatin and radiation treatments

PURPOSE: To investigate the extent of non-homologous end-joining (NHEJ) in the mechanism of cisplatin radiosensitization. MATERIALS AND METHODS: Ku80-deficient cells are deficient in the non-homologous DNA double-strand break repair process, while the wild-type MEF cells maintain full mammalian cell repair capabilities. Both cell lines were exposed to clinically applicable doses of cisplatin (1, 3 and 6 microg x ml(-1)) for 1 h immediately before exposure to 250 kV X-rays. Radiation responses were plotted for each cell line and for all doses of cisplatin to observe relative levels of radiosensitization. Split-dose experiments were also performed on each cell line to measure levels of sublethal damage repair. RESULTS: Radiosensitization was observed in the wild-type cells but not in the Ku80 cells when treated with a combination of 1 microg x ml(-1) cisplatin followed by X-rays, implying that the NHEJ pathway may play a large role in cisplatin radiosensitization. Concurrent administration of this cisplatin dose with radiation produced similar levels of radiosensitization. Conversely, 3 and 6 microg x ml(-1) cisplatin applied immediately before radiation revealed an increasing resistance to radiation in both cell lines--possibly due to resistant subpopulations of cells remaining after subsequent lethal doses of cisplatin. Further experiments revealed that the high concentrations of cisplatin did not alter cell cycle distribution. Finally, split-dose experiments revealed that the NHEJ pathway also plays a significant role in sublethal damage repair. CONCLUSIONS: The study reveals that clinically applicable doses of cisplatin treatment results in the radiosensitization of mammalian cells due to the inhibition of the operation of NHEJ.     

MR imaging of the knee joint plain, following intra-articular administration of gadolinium DTPA, saline and air

Noninvasive MRI of the knee joint yields a great deal of information on soft parts (ligaments, capsule, free fluid, menisci, cartilage) and bones. The image is changed by intraarticular administration of air and of small quantities of fluids supply many signals, such as gadolinium DTPA solution. The results and possibilities of application are discussed.     

Localization of Tc-99m DTPA in a chordoma.

The authors report a patient with chordoma that was demonstrated as a photopenic region on Tc-99m MDP bone imaging but that localized Tc-99m DTPA intensely. An explanation for the discrepancy is discussed. Complementary Tc-99m DTPA imaging in the preoperative evaluation of sacral tumors is suggested.     

Biodistribution and magnetic resonance imaging of cross-linked DTPA polysaccharides.

Large polysaccharide complexes, cross-linked with DTPA and chelated with gadolinium have been tested for various potential uses for magnetic resonance imaging (MRI) in rats. Biodistribution and pharmacokinetic data for several of the soluble polymers are presented and compared with Gd-DTPA and GdCl3. By varying the initial polysaccharide length and ratio of DTPA to glucose units, polymers of molecular weights (mol wt) from 17,000 to several million were formed, giving soluble material, gels, or particles. The larger polymers (mol wt greater than 100,000) demonstrate prolonged enhancement of the intravascular space, striking renal enhancement, and moderate hepatic uptake. Small particulate material (less than 10 microns) was also successfully used for intravascular enhancement. The material is metabolized and excreted in urine.