DTPA Administration Research Articles

Imaging findings of giant cell tumor of tendon sheath

Objective To explore the imaging features of giant cell tumor of tendon sheath(GCTTS) so as to improve the accuracy of imaging diagnosis. Methods Thirty-nine cases of GCTTS confirmed by pathological examination were retrospectively analyzed.Of the 39 cases, 32 were diffuse form and 7 were localized form.Seventeen patients underwent X-ray examination,18 had CT pain examination,37 had pain MR imaging and 17 had contrast-enhanced MR imaging. Results X-ray showed local soft tissue masswith slightly high density, and the adjacent bones were shown destruction or erosion tovarious degrees(10/17). No obvious calcification and periosteal reaction were shown. CT scans could provide images better than X-ray films.CT showed local soft tissue masses in the peri-articular muscle gaps. Some tumors were lobulated with cross-jointed growth(8/18),and the adjacent bones were shown destruction or erosion tovarious degrees (11/18) .No obvious calcification and periosteal reaction were shown. On MRI, most cases were isointense on T1WI (32/37) ,and hyperintense on T2WI (27/37) . Most cases tended to be heterogeneously enhanced following Gd- DTPA administration (14/17) .The lesions were typically located adjacent to a tendon or partially/completely encasing it. Conclusions The imaging findings of GCTTS have some certain characteristics. MRI is able to depict the characteristic internal signal of GCTT and its relationship with adjacent tissues, which is valuable for diagnosis, treatment and follow-up. Key words: Giant cell tumor; Tomography, X-ray computed; Magnetic resonance imaging; Diagnosis

Calcium and Zinc DTPA Administration for Internal Contamination with Plutonium-238 and Americium-241

The accidental or intentional release of plutonium or americium can cause acute and long term adverse health effects if they enter the human body by ingestion, inhalation, or injection. These effects can be prevented by rapid removal of these radionuclides by chelators such as calcium or zinc diethylenetriaminepentaacetate (calcium or zinc DTPA). These compounds have been shown to be efficacious in enhancing the elimination of members of the actinide family particularly plutonium and americium when administered intravenously or by nebulizer. The efficacy and adverse effects profile depend on several factors that include the route of internalization of the actinide, the type, and route time of administration of the chelator, and whether the calcium or zinc salt of DTPA is used. Current and future research efforts should be directed at overcoming limitations associated with the use of these complex drugs by using innovative methods that can enhance their structural and therapeutic properties.

A decennial booster dose of reduced antigen content diphtheria, tetanus, acellular pertussis vaccine ( Boostrix™) is immunogenic and well tolerated in adults

Reduced-antigen-content diphtheria–tetanus–acellular-pertussis (dTpa) vaccines are predominantly recommended for once-in-a-lifetime use. A second dTpa ( Boostrix™, GlaxoSmithKline Biologicals) administration in 164 adults previously vaccinated with dTpa 10 years previously was evaluated. Before the decennial booster, 89.4% and 94.8% subjects were seroprotected (antibodies ≥0.1 IU/mL) for diphtheria and tetanus, respectively. One-month post-booster, all subjects were seroprotected/seropositive against all vaccine antigens. Robust GMC increases indicated a booster response similar to the first booster. The decennial booster was well tolerated without serious adverse events, consistent with product experience. This study supports replacing traditional Td boosters with dTpa, and use of Boostrix™ as a decennial booster. This study is registered at www.clinicaltrials.com NCT00548171.

Quantitative evaluation of blood–cerebrospinal fluid barrier permeability in the rat with experimental meningitis using magnetic resonance imaging

Disruption of the blood–brain barrier (BBB) and/or the blood–cerebrospinal fluid barrier (BCSFB) is thought to be one of the major pathophysiological consequences of meningitis and contributes to the development of adverse neurological outcomes. In order to clarify this hypothesis further, we sequentially quantified the permeability of these barriers with magnetic resonance imaging (MRI) contrast enhancement using gadolinium–diethylene triamine pentaacetic acid (Gd–DTPA) in rats with various experimentally-induced meningitis. Meningeal inflammation was elicited by an intracisternal injection of interleukin (IL)-1β, prostaglandin (PG) E 2, or lipopolysaccharide (LPS). Barrier permeability was calculated from the gadolinium-enhancement ratio (GER) in the subarachnoid space (SAS). The secretion of Gd–DTPA into the SAS was monitored by T1-weighted imaging after an intravenous injection of Gd–DTPA. As a significant linear correlation was observed between the GER and the standard solution, the concentration of the secreted Gd–DTPA were determined from the GER. The maximal intensity in SAS was detected at 5 min after Gd–DTPA administration and it declined gradually. Among the inflammatory agents, IL-1β was found to induce the most severe meningitis as determined from the GER. The concentration of Gd–DTPA in the SAS increased in a dose-dependent manner following IL-1β intracisternal injection. On the other hand, no significant changes in signal intensity of the brain parenchymal areas due to IL-1β injection were observed. The findings suggest that the permeability of the BCSFB can be evaluated quantitatively by calculating the GER. MRI with Gd–DTPA provides a useful method to monitor the change in the permeability to the brain barriers.

Treatment of PuO2 Lung Contamination using a Dry Powder Formulation of DTPA

Lung contamination can result from accidental release of actinides such as Pu and Am. The therapeutic approach to reduce the effective radiation dose is to remove the α-emitting radionuclides from the body by promoting their decorporation. DTPA is the recommended treatment of internal contamina-tion by plutonium. The present work investigates the decorporation efficacy of a dry powder formulation of CaNa3-DTPA on a pulmonary contamination with PuO2. Sprague-Dawley rats were exposed to PuO2 aerosols, and 2 hours later received an intratracheal insufflation of CaNa3-DTPA (18.2 ± 1.4 µmol /kg) formulated into porous particles. Urines were collected daily for 7 days. Initial lung deposit (ILD) was determined by X ray spectrometry counting 7 days post-inhalation. Fourteen days post-inhalation, rats were euthanized, liver, femurs and lungs were collected and broncho alveolar lavages (BAL) were carried out. The total alpha activity of samples was measured by liquid scintillation counting in BAL, BAL cells and BAL fluids. The ILDs of untreated rats and DTPA-treated rats were respectively 15.6 ± 2.3 and 13.6 ± 2.3 kBq. The cumulative activity urinary excretion over 7 days was 7-fold higher after DTPA administration as compared to untreated rats, and represented approximately 7% of the ILD for DTPA-treated animals. In the main retention tissues, liver and skeleton, the deposit of activity in DTPA-treated rats was less than 5% of the one of untreated animals (1.13% of ILD in liver of untreated rats vs 0.05% in DTPA-treated rats; 2.75% in skeleton vs 0.1%). Distribution of alpha activity within lungs was determined. Activity recovered in BAL fluids from DTPA-treated rats was 7.3-times lower than in BAL fluids from untreated animals. Although the activity associ-ated with BAL cells tended to decrease, the difference between the 2 groups remained non significant, suggesting that pulmonary surfactant and/or serum-derived proteins represented the major accessible lung compartment for DTPA decorporation. However, no significant decrease in whole lung activity was ob-tained. Our study shows the efficacy of a dry DTPA powder on actinide decorporation. By inhibiting ac-tinide deposit in skeleton and liver, a limitation of the dose delivered to these tissues is expected, thus limiting the risks for radiation-induced diseases. In addition, DTPA treatment modified distribution of activity within lungs. It is generally admitted that soluble compounds leading to more homogeneous irra-diation of the lungs cause higher damage than insoluble forms. The decorporation of the most soluble fraction of radionuclide present in BAL fluids, could thus limit lung damage.

MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF PERIPHERAL NERVE SHEATH TUMORS OF THE CANINE BRACHIAL PLEXUS IN 18 DOGS

Magnetic resonance imaging (MRI) examinations from 18 dogs with a histologically confirmed peripheral nerve sheath tumor (PNST) of the brachial plexus were assessed retrospectively. Almost half (8/18) had a diffuse thickening of the brachial plexus nerve(s), six of which extended into the vertebral canal. The other 10/18 dogs had a nodule or mass in the axilla (1.2-338 cm3). Seven of those 10 masses also had diffuse nerve sheath thickening, three of which extended into the vertebral canal. The majority of tumors were hyperintense to muscle on T2-weighted images and isointense on T1-weighted images. Eight of 18 PNSTs had only minimal to mild contrast enhancement and many (13/18) enhanced heterogeneously following gadolinium DTPA administration. Transverse plane images with a large enough field of view (FOV) to include both axillae and the vertebral canal were essential, allowing in-slice comparison to detect lesions by asymmetry of structures. Higher resolution, smaller FOV, multiplanar examination of the cervicothoracic spine was important for appreciating nerve root and foraminal involvement. Short tau inversion recovery, T2-weighted, pre and postcontrast T1-weighted pulse sequences were all useful. Contrast enhancement was critical to detecting subtle diffuse nerve sheath involvement or small isointense nodules, and for accurately identifying the full extent of disease. Some canine brachial plexus tumors can be challenging to detect, requiring a rigorous multiplanar multi-pulse sequence MRI examination.

Contrast-enhanced hepatic mri: Comparison of half-dose and standard-dose gadolinium dtpa administration in lesion characterization with T1-weighted gradient echo sequences

The objective of this article was to compare half-dose (0.05 mm/kg) gadolinium-enhanced dynamic hepatic MR imaging to standard doses (0.10 mm/kg). Eighteen patients for follow-up hepatic MR received 0.05 mm/kg of gadolinium DTPA dynamically with gradient-echo imaging. Imaging parameters were identical to a 0.10-mm/kg study; patients were imaged during multiple phases of contrast enhancement. Two readers assessed for enhancement patterns and characterization. Quantitative signal-to-noise ratios (S/N) were obtained for abdominal viscera and contrast-to-noise ratios (C/N) were obtained on up to three lesions. No significant difference for the arterial dominant phase ( P > 0.05) was found. Significant differences were found in all categories during the portal venous phase (except pancreas) and equilibrium phase (except liver). Lesion C/N ratios were not significant at any point ( P > 0.05). Sixty-two out of 64 lesions (97%) were identically characterized. Therefore, half-dose dynamic gadolinium-enhanced MR may have diagnostic value.

Small hepatocellular carcinoma on magnetic resonance imaging. Relation of signal intensity to angiographic and clinicopathologic findings.

The authors discuss the clinicopathologic features and angiographic vascularity of various signal intensity patterns on magnetic resonance (MR) imaging of small hepatocellular carcinomas (HCCs). Magnetic resonance images of 88 resected HCCs (< or = 3 cm) were obtained using T1- and T2-weighted spin-echo images and T1-weighted images after gadolinium (Gd)-DTPA administration. Images were compared with angiographic and histopathologic findings. Forty HCCs (45%) were depicted on T1-weighted images, 51 (58%) on T2-weighted images, and 41 (49%) on T1-weighted images after Gd-DTPA administration. Overall, 64 (76%) were found on at least one image. On T1-weighted images, hyperintense HCCs histologically showed fatty metamorphosis and portal tracts within the tumor. On T2-weighted images, HCC hyperintensity correlated with expansive growth, peliotic change, and hypervascularity. By contrast, HCCs that were undetected or hypointense on T2-weighted images were well differentiated with replacing growth and portal tracts. On T1-weighted images after Gd-DTPA, hyperintense HCCs had peliotic change; undetected HCCs were well differentiated and hypovascular. Histologic grade, vascularity, portal tracts and peliotic change correlate with MR signal intensity. For hyperintense HCCs on T1-weighted images and hypo- or isointense HCCs on T2-weighted images, treatment methods must be assigned with the consideration that HCCs may be receiving transsinusoidal and portal blood supplies.

Decorporation of thorium-228 from the rat by 3,4,3-LIHOPO and DTPA after simulated wound contamination

1. With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 228Th nitrate from the rat after subcutaneous (sc) and intramuscular (im) injection to simulate wound contamination. The commencement of treatment was delayed 30 min, 6 h or 1 d and the animals killed at 7 d. 2. In all cases 3,4,3-LIHOPO was appreciably more effective than DTPA although the efficacy of treatment and the relative effectiveness of the ligands decreased rapidly with their delay in administration. 3. Optimum removal with both ligands occurred when initial local administration at 30 min after exposure was followed by repeated intraperitoneal injection at 6 h, 1, 2 and 3 d. Under these conditions the body content of 228Th was reduced to 20% of controls after sc injection and 15% after im injection. The corresponding values using repeated DTPA administration were 80% and 54%. 4. It is concluded that 3,4,3-LIHOPO represents, potentially, a considerable advance on DTPA, the current agent of choice for the treatment of wounds contaminated by 228Th.

3-D imaging of the CNS

3-D gradient echo techniques, and in particular FLASH, represent a significant advance in MR imaging strategy allowing thin section, high resolution imaging through a large region of interest. Anatomical areas of application include the brain, spine, and extremities, although the majority of work to date has been performed in the brain. Superior T1 contrast and thus sensitivity to the presence of GdDTPA is achieved with 3-D FLASH when compared to 2-D spin echo technique. There is marked arterial and venous enhancement following Gd DTPA administration on 3-D FLASH, a less common finding with 2-D spin echo. Enhancement of the falx and tentorium is also more prominent. From a single data acquisition, requiring less than 11 min of scan time, high resolution reformatted sagittal, coronal, and axial images can obtained in addition to sections in any arbitrary plane. Tissue segmentation techniques can be applied and lesions displayed in three dimensions. These results may lead to the replacement of 2-D spin echo with 3-D FLASH for high resolution T1-weighted MR imaging of the CNS, particularly in the study of mass lesions and structural anomalies. The application of similar T2-weighted gradient echo techniques may follow, however the signal-to-noise ratio which can be achieved remains a potential limitation.

Oral Zn-DTPA therapy for reducing 141Ce retention in suckling rats.

In neonatal rats DTPA reduced the intestinal retention of cerium ingested as an additive in its chloride form to milk. It also reduced retention of absorbed cerium. A similar decrease of cerium retention in gut and whole body was obtained after simultaneous or 24 hours' delayed DTPA administration.

Effect of Age on the Efficacy of Zn-Diethylenetriaminepentaacetic Acid Therapy for Removal of Am and Pu from Beagles

Decorporation of intravenously injected monomeric 241Am and 237+239Pu by the administration of 30 mumole Zn-diethylenetriaminepentaacetic acid (DTPA)/kg each day beginning 2 weeks after radionuclide injection was compared in beagles entered into the experiment when 3 months (juveniles). 1.9 years (young adults), or 10 years (mature adults) old and studied for about 5 months. DTPA therapy was most effective in the juvenile dogs and least effective in the mature adults. Retention of 241Am in the liver decreased from a pretreatment value for adults of about 50% of the injected activity to about 10% in the mature adults and less than 1% in the young adults at 140 days of treatment, while the liver retention of juveniles decreased from pretreatment values of about 16% to undetectable levels by 28 days of treatment. Plutonium retention in the liver decreased from adult pretreatment levels of about 30% of the injected activity (corrected for radioactive decay) to near 10% in the mature adults and 6% in the young adults at 140 days of treatment, while juvenile liver retention decreased from pretreatment values near 15% to undetectable levels by 56 days of treatment. Nonliver Am retention (mainly skeleton) decreased in mature adults from pretreatment values of about 45% of the injected activity to near 25%, in young adults from 35 to 20%, and in juveniles from roughly 70 to 9% by 140 days of DTPA administration. Nonliver Pu retention decreased from pretreatment values of about 50% of the injected activity (corrected for radioactive decay) for mature and young adults to about 30% by 140 days and from 75 to 16% in juveniles over the time period.

Efficacy of different DTPA treatment schedules for removal of 234Th from simulated wounds in rats.

The translocation of 234Th from a simulated wound site and the efficacy of DTPA administration, as a function of the thorium compound injected as well as the DTPA treatment schedule, have been investigated in rats. Much more 234Th injected as citrate was translocated from the injection site than after administration as nitrate, whereas the distribution pattern of 234Th translocated to the various tissues was nearly identical for both 234Th compounds. Combined local and systematic treatment with DTPA was equally or more effective than each of the treatments alone in reducing the retention of 234Th at the injection site and in the organs.

Pu and Am Decorporation in Beagles: Effects of Magnitude of Initial Ca-DTPA Injection upon Chelation Efficacy

To investigate the effects of magnitude of initial DTPA injection upon chelation efficacy, five young adult beagles were each given an intravenous injection of /sup 237 +239/Pu(IV) citrate + /sup 241/Am(III) citrate, followed by a single intravenous injection of Ca-DTPA 0.5 hr later. Amounts of this chelating agent administered were 3, 10, 30, 100, and 300 ..mu..mole Ca-DTPA/kg body mass. Animals were sacrificed 7 days later. Total-body retention of both plutonium and americium was influenced strongly by the amount of DTPA administered, although the removal of Pu by DTPA was less pronounced than that of Am; and in the range of 30 ..mu..mole/kg, an increase of DTPA administration by a factor of 2 resulted in only a 25% decrease in residual body content. Plutonium retention at 7 days was reduced from about 77% in the dog given 3 ..mu..mole/kg to 14% in the animal injected with 300 ..mu..mole/kg. Corresponding values for americium were 40 and 9%. Also, liver content of both Pu and Am was reduced significantly by larger amounts of administered DTPA, decreasing from 18 to 2% for Pu with increasing levels of DTPA, and from 21 to 1% for Am. If there is a level of Ca-DTPA administrationmore » at 30 min after injection in a beagle at which no additional chelation of Pu or Am is produced with increasing dosage, it is greater than 300 ..mu..mole/kg. In a 70-kg human, this would be equivalent to the injection of 10 g Ca-DTPA.« less

Action of DTPA on Hepatic Plutonium: II. DTPA-Induced Removal of Monomeric Plutonium from Mouse Liver Parenchymal Cells

Liver parenchymal cells were isolated 6 and 24 hr following the administration of diethylenetriaminepentaacetic acid (DTPA, 0.25 mmole/kg) to mice previously injected with /sup 239/Pu-citrate (4.4 ..mu..Ci/kg). Isolated parenchymal cells contained 440 dpm Pu/10/sup 6/ cells at 24 hr after Pu injection, just prior to DTPA administration. The PU content decreased to 330 dpm/10/sup 6/ cells at 6 hr and 140 dpm/10/sup 6/ cells at 24 hr after DTPA administration. Thus DTPA induced a striking decrease in the Pu content of isolated liver parenchymal cells. Parenchymal cells isolated from control mice not treated with DTPA changed little in Pu content from 24 to 48 hr after Pu injection. By 24 hr after DTPA treatment, the decrease in the Pu content of isolated liver parenchymal cells could account for the DTPA-induced release of Pu from the intact liver. Thus in the liver DTPA appears to act preferentially on the Pu associated with parenchymal cells. Liver parenchymal cells isolated 6 hr after DTPA administration and containing 330 dpm Pu/10/sup 6/ cells were incubated in vitro in the absence of added DTPA. After 18 hr of incubation the cells contained 130 dpm Pu/10/sup 6/ cells. This level corresponds to the level observed inmore » cells isolated 24 hr after DTPA administration. Cells isolated from untreated mice lost only 15% of their Pu content during a similar in vitro incubation. Thus, by 6 hr after DTPA administration to the mouse, isolated liver parenchymal cells appeared to retain their ability to release Pu in vitro with no need for additional exposure to DTPA. The physiological significance of this finding is discussed.« less

Action of DTPA on Hepatic Plutonium: I. Quantitation of the DTPA-Induced Biliary Excretion of Plutonium in the Rat

Rats received an intravenous injection of 0.1 μCi of ${}^{239}{\rm Pu}\text{-citrate}$ (approx 0.5 μCi/kg). At 24 hr after Pu injection, the bile ducts were cannulated and diethylenetriaminepentaacetic acid (DTPA, 0.25 mmole/kg) was injected intravenously. The amount of Pu appearing in the bile during the first 24 hr after DTPA injection was determined. In addition, the decrease in Pu content of the liver 24 hr after DTPA administration was measured in both bile duct-cannulated and noncannulated rats and compared to the amount of Pu appearing in the bile. Bile collected from control rats receiving saline instead of DTPA contained 0.40 ± 0.08 nCi of Pu (mean ± SE, n = 3), while bile collected for 24 hr after DTPA administration contained 7.2 ± 0.4 nCi Pu (mean ± SE, n = 6). Thus, DTPA administration brought about a striking increase in biliary Pu excretion. The mean decrease in liver Pu content 24 hr after DTPA administration to rats whose bile ducts were not cannulated was 7.4 ± 1.4 n...