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G L McIntire

Publications and source records attributed to G L McIntire.

18 recordsLinked to original sources
PubMed2000

Time course of nodal enhancement with CT X-ray nanoparticle contrast agents: effect of particle size and chemical structure.

RATIONALE AND OBJECTIVES: Levels of CT enhancement in rabbit lymph nodes were followed with time after subcutaneous injection of four iodinated, insoluble nanoparticle contrast agents to provide experimental support for the hypothesis that clearance of these agents is related to the chemical structure of the agent itself. The impact of particle size was also studied. METHODS: Subcutaneous injections (2 x 0.25 mL) were made in the dorsum of rabbit paws with 15% suspensions of four nanoparticle contrast agents. Images were obtained at 4, 10, 24, 48, and 72 hours and 5, 7, and 14 days after injection. Average attenuation (in Hounsfield units [HU]), node volume, and total iodine uptake were estimated from the CT scans for each lymph node at each time point. RESULTS: All the agents provided adequate enhancement of both the popliteal and axillary lymph nodes of the rabbit (ie, > delta100 HU). Lymph node volume appears to be related to the persistence of enhancement, with long-lived agents demonstrating the greatest increase in size. The rate of clearance from the lymph nodes is related to the structure of the agent. CONCLUSIONS: Clearance of insoluble, iodinated nanoparticle contrast agents from lymph nodes can be modulated by changes in the structure of the agent itself. Using the same agent, smaller particles deliver material to the lymph nodes more quickly and clear more quickly.

Animals↗
PubMed2000

Long-term effect of irradiation on lymph node uptake of interstitially delivered nanoparticulate contrast media.

RATIONALE AND OBJECTIVES: To characterize the long-term effects of therapeutic doses of ionizing radiation on the uptake and distribution of percutaneously delivered particulate contrast media in normal lymph nodes. METHODS: Two milliliters of an iodinated nanoparticle suspension (76 mg I/mL) was injected subcutaneously or submucosally into nine normal adult beagles. Region of interest analysis was used to estimate the volume, attenuation, and iodine concentration of opacified targeted lymph nodes and nonopacifled contralateral nodes on 24-hour postinjection CT images. All lymph nodes were then irradiated with 50 Gy in 25 fractions of 2 Gy/d. Contrast-enhanced quantitative CT was repeated 12 months after irradiation. RESULTS: Contrast-enhanced nodes averaged 2.3+/-0.8 times the volume of nonenhanced contralateral nodes before irradiation. The mean attenuation of contrast-enhanced nodes increased to 305 to 380 Hounsfield units from a pre-enhancement value of approximately 25 Hounsfield units. Opacified node volumes after irradiation averaged 61% to 86% of preirradiation volumes but were generally not statistically different. Contrast uptake assessed by average attenuation and iodine concentration decreased significantly by an average of 17% to 22% after irradiation and was significantly less than preirradiation uptake. Qualitatively, irradiated nodes generally appeared smaller than nonirradiated nodes, but the distribution pattern of contrast media did not appear to be appreciably altered. CONCLUSIONS: Lymph node irradiation resulted in only minimal decreases in contrast media uptake and node volume at 12 months. These effects presumably would not appreciably alter the potential clinical value of indirect lymphography for evaluating patients undergoing radiation therapy.

Animals↗
PubMed2000

Pharmacokinetics and hepatic disposition of bis[1-(ethoxycarbonyl)propyl]5-acetylamino-2,4,6-triiodoisophthalate in rats and isolated perfused rat livers.

Bis[1-(Ethoxycarbonyl)propyl]5-acetylamino-2,4,6- triiodoisophthalate+ (NC 68183) was designed as a new computed tomography imaging agent. The purpose of this study was to determine the pharmacokinetics and metabolism of NC 68183 in conscious rats and in the isolated perfused rat liver. Animals were i.v. dosed at 69 and 690 mg of iodine/kg. Blood samples were collected at 5, 15, 30, and 60 min, and 7 days after dosing. Tissue samples (liver, kidney, and spleen) were taken at 60 min and 7 days after dosing. NC 68183 was cleared from blood in first order kinetics following an i.v. administration of 69 mg I/kg. The volume of distribution (Vss) at steady state and elimination half-life (t(1/2)) were estimated as 24 ml and 11 min. The clearance of NC 68183 from blood was changed to zero-order kinetics following administration of 690 mg/kg, and its elimination rate was 16 microg I/ml.min. The liver and spleen were the only tissues to have the nanoparticle residue at day 7 following administration. NC 68183 (75 mg of agent, 35 mg of I) was injected into the isolated perfused rat liver system. Bile flow increased from 1.0 to 1.3 microl/min/g liver following administration. The biliary excretion rate maximum was estimated as 11 microg/min/g liver. The metabolite was identified using liquid chromatography/mass spectrometry as a monocarboxylic acid product, which exclusively excreted into the bile in a soluble iodinated metabolite. Pharmacokinetics data suggested that NC 68183 primarily resides in the blood pool following an i.v. administration with a plasma half-life appropriate for blood pool imaging.

Animals↗
PubMed1999

CT imaging of intrathoracic lymph nodes in dogs with bronchoscopically administered iodinated nanoparticles.

RATIONALE AND OBJECTIVES: The purpose of the study was to determine if airway instillation of iodinated nanoparticles results in contrast material enhancement of tracheobronchial lymph nodes in dogs. MATERIALS AND METHODS: Eight dogs underwent intrabronchial instillation of iodinated nanoparticles; six dogs received 900 mg each, and two dogs received 450 mg each. Spiral computed tomography (CT) was then performed 2-34 days later. RESULTS: CT scans obtained 2 days after instillation showed the presence of contrast material within the lung parenchyma but no nodal enhancement. Scans obtained 6-34 days after instillation showed enhancement of the right, left, and middle tracheobronchial lymph nodes (analogous to the mediastinal nodes in humans). Mean nodal attenuation on CT images was 117 HU +/- 43, and the mean nodal volume was 129 mm3 +/- 113. Histologic specimens of the nodes showed macrophage hyperplasia. CONCLUSION: Iodinated nanoparticles instilled into small airways are transported to the tracheobronchial lymph nodes, where they result in contrast enhancement.

Administration, Topical↗
PubMed1999

Lymph node extraction of radiopaque nanoparticulates in the rabbit as measured in vivo with CT.

RATIONALE AND OBJECTIVES: The purpose of this study was to estimate in vivo extraction of lymphographic material in the popliteal node of the rabbit. MATERIALS AND METHODS: Serial quantitative computed tomography (CT) of target tissues in four legs of two rabbits was performed after subcutaneous injection of an improved lymphographic contrast agent. Massage was used as a lymphotrophic intervention. RESULTS: At 15 minutes, the mean change in Hounsfield units measured 815 in the popliteal node, 219 in afferent lymphatic vessels, and 127 in efferent lymphatic vessels. The nodal extraction of nanoparticulates from the lymph was approximately 55%. Nodal massage allowed the amount of nanoparticulate remaining in sinusoidal lymph to be estimated. CONCLUSION: Functional CT performed with timed studies, proper radiopaque materials, and physiologic interventions can depict in vivo lymphatic physiology under minimally invasive conditions.

Animals↗
PubMed1999

Blood pool and liver enhancement in CT with liposomal lodixanol: comparison with lohexol.

RATIONALE AND OBJECTIVES: The authors compared the time course and blood pool and hepatic enhancement of three different doses of liposomal iodixanol with those of iohexol. MATERIALS AND METHODS: A liposomal iodixanol formulation was prepared with 200 mg of iodine per milliliter total and 80 mg of iodine per milliliter encapsulated. Twelve normal New Zealand white rabbits divided into four groups received 75-, 100-, or 150-mg encapsulated iodine per kilogram doses of liposomal iodixanol or 2 mL/kg iohexol with 300 mg of iodine per milliliter. A liver section was scanned with serial computed tomography (CT) before the injection, immediately afterward, and at 1-minute intervals for 10 minutes. Region-of-interest measurements of the aorta and liver were plotted at each time point, and contrast enhancement was plotted as a function of time and iodine dose. RESULTS: All liposomal iodixanol doses produced greater liver enhancement than iohexol. Results were significant (P < .05) for 100 mg and 150 mg iodine per kilogram dose groups at time points beyond 2 minutes. Peak hepatic enhancement (change in attenuation) was 54.9 HU +/- 7.6 with iohexol, compared with 59.6 HU +/- 6.1, 73.3 HU +/- 3.6, and 104.1 HU +/- 8.8 for 75, 100, and 150 mg encapsulated iodine per kilogram doses, respectively. Hepatic enhancement increased rapidly after injection of liposomal iodixanol, plateauing 2-3 minutes later. Blood pool enhancement decreased rapidly. Steady-state liver enhancement with liposomal iodixanol increased linearly with dose. Aortic enhancement was greater with iohexol. CONCLUSION: Liposomal iodixanol yielded greater hepatic enhancement at lower total iodine doses than iohexol. Although liver enhancement occurred rapidly after injection, blood pool enhancement was brief.

Animals↗
PubMed1999

Interstitial MR and CT lymphography with Gd-dTPA-co-alpha, omega-diaminoPEG(1450) and Gd-dTPA-co-1,6-diaminohexane polymers: preliminary experience.

RATIONALE AND OBJECTIVES: The authors assessed the efficacy of two gadolinium-based polymers used as lymphotrophic contrast media for computed tomography (CT) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Two gadolinium-based polymers, gadolinium diethylenetriaminepentaacetic acid (DTPA)-co-1,6-diaminohexane (NC 22181) and Gd-DTPA-co-alpha, omega-diamino-polyethylene glycol(1450) (NC-66368), were formulated at a concentration of 80 mmol/L gadolinium. Doses of 0.1, 0.25, 1.0, or 2.0 mL per paw were administered subcutaneously into the hindpaws of normal rabbits. Spin-echo T1-weighted MR imaging (1.5 T) of rabbit popliteal and iliac nodes was performed before and immediately, 10 minutes, 2-3 hours, and 24 hours after injection. CT was performed 2-3 hours after injection of the high doses only. RESULTS: MR imaging revealed prompt enhancement of the popliteal nodes with both polymers at doses of 0.25 mL and above. For doses of 1.0 mL or less per paw, nodal percentage enhancement was maximal at 2 hours and then declined at 24 hours. At the highest doses, however, a reservoir of subcutaneous contrast material remained at the injection site and resulted in peak enhancement at 24 hours. At CT, popliteal node enhancement was faintly visible 2-3 hours after the administration of NC 22181. At lower doses, no enhancement was appreciable at CT. CONCLUSION: At 80 mmol/L formulations, the two gadolinium-based polymers provide excellent popliteal nodal enhancement on MR images. In addition, high doses of one polymer (NC 22181) were sufficiently concentrated in popliteal nodes to be visible on CT scans. Thus, this agent may be useful for both CT and MR lymphography.

Animals↗
PubMed1999

Lymph node uptake of interstitially delivered particulate contrast media before and after irradiation in dogs.

RATIONALE AND OBJECTIVES: The authors' purpose was to assess the effects of ionizing radiation on the uptake and distribution of interstitially delivered particulate contrast medium in normal lymph nodes in dogs. MATERIALS AND METHODS: Two milliliters of an iodinated nanoparticle suspension (NC 67722 Sterile Suspension, 76 mg of iodine per milliliter) was injected subcutaneously or submucosally into nine normal adult beagle dogs. Targeted lymph node groups were evaluated with computed tomography (CT). Region-of-interest analysis was used to estimate volume, attenuation, and iodine concentration of the opacified nodes and nonopacified contralateral nodes on CT images obtained before and 24 hours after the injection. All right-sided and some left-sided lymph nodes were irradiated with 50 Gy in 25 fractions of 2 Gy per day, beginning 28-35 days after the CT examination. Contrast medium administration and quantitative CT imaging were performed again 3 months after irradiation. RESULTS: Contrast material uptake resulted in a twofold increase in node volume before irradiation (P < .0001). Mean attenuation of contrast-enhanced nodes increased to 230-330 HU from a precontrast enhancement value of 36.5 HU. After irradiation, opacified node volumes decreased to approximately 25%-50% of their preirradiation volumes (P < .02). Contrast material uptake decreased 10%-15% after irradiation but was not significantly less than preirradiation uptake. Qualitatively, no substantial difference in contrast material distribution existed between irradiated and nonirradiated nodes. CONCLUSION: An elective irradiation dose decreased lymph node size, but the imaging characteristics of opacification were not otherwise appreciably altered 3 months after irradiation.

Analysis of Variance↗
PubMed1998

Pulmonary delivery of nanoparticles of insoluble, iodinated CT X-ray contrast agents to lung draining lymph nodes in dogs.

Lung cancer continues to be a leading cause of death around the world. Staging of this disease is critically dependent upon the involvement or noninvolvement of the lymph nodes which drain the region of lung containing the lesion/tumor. Palpation, unenhanced CT, and lymph node excision (i.e., mediastinectomy) are currently used to ascertain the status of these regional draining lymph nodes. The work reported herein details the first efforts toward the pulmonary instillation of iodinated nanoparticles for contrast-enhanced CT of lung draining lymph nodes. The data reflect the impact of dose, time post instillation, and formulation (surfactant) upon the observed CT enhancement of the tracheobronchial lymph nodes of beagle dogs. In addition, initial safety is discussed with both macroscopic and microscopic observations. The results indicate that pulmonary instillation of small volumes of iodinated nanoparticles could be successfully used to aid staging of lung cancer by CT imaging.

Administration, Inhalation↗
PubMed1995

Hepatic imaging with iodinated nanoparticles: a comparison with iohexol in rabbits.

RATIONALE AND OBJECTIVES: We evaluated the efficacy of a particulate computed tomography (CT) contrast agent in an animal model of focal liver disease. METHODS: Ethyl ester of diatrizoic acid (EEDA) is an iodinated (89 mg I/ml) nanoparticulate (200 nm) contrast agent intended for intravenous use that is currently undergoing preclinical testing in our laboratory. Focal liver abscesses were created in 11 New Zealand White rabbits. Iohexol and EEDA were administered to each animal on different days. CT scanning was performed at intervals following contrast agent administration. Liver and abscess enhancement were measured and compared. Dynamic imaging experiments in normal animals were also performed using both agents. RESULTS: EEDA resulted in significantly greater enhancement of the liver and liver-to-abscess contrast than did iohexol at all time points beyond 5 min at approximately 25% of the total iodine load. During dynamic imaging, liver and aortic enhancement were greater with EEDA than with iohexol, except during a 20- to 40-sec period immediately following contrast agent administration. CONCLUSION: EEDA is superior to iohexol for imaging liver abscesses. Our results suggest that liver-directed agents such as EEDA may prove to be more efficacious than currently available extracellular agents designed for liver CT scanning.

Animals↗
PubMed1995

The electrophoretic mobility of tripeptides as a function of pH and ionic strength: comparison with iontophoretic flux data.

Capillary electrophoresis (CE) is an extremely efficient separations tool which can also be used to determine fundamental molecular parameters, e.g., the electrophoretic mobility of a molecule. We have studied the changes in the CE estimated electrophoretic mobility of thyrotropin releasing hormone (TRH) as a function of pH and ionic strength. Further, we have used CE to estimate the mobilities of two synthetic analogs of TRH to examine the behavior of positive (basic) and negative (acidic) peptides under the conditions of this work. These data were then compared with literature values of iontophoretic flux of these molecules under similar formulation conditions. Our results suggest that CE could potentially assist formulation optimization for the iontophoretic delivery of peptides.

Amino Acid Sequence↗
PubMed1994

Percutaneous computed tomography lymphography in the rabbit by subcutaneously injected nanoparticulates.

RATIONALE AND OBJECTIVES: Surgical lymphangiography is infrequently used in staging cancer because of its inherent limitations. Radiopaque nanoparticulates target lymph nodes draining interstitial tissues and could make percutaneous lymphography feasible. METHODS: Experimental nanoparticulate contrast agent formulations were injected subcutaneously in the forepaw or hindpaw of normal rabbits or rabbits with induced reactive nodal hyperplasia. Axillary and popliteal nodes were imaged with thin-section computed tomography (CT) using quantitative methods to measure node enhancement. Dose-response (0.1-2.0 ml) and time course (4 hr to 10 weeks) of enhancement were assessed. RESULTS: Nodal enhancement above 100 Hounsfield units was consistently obtained. Enhancement was significantly related to dose and peaked at 10 hr with slow washout over the observation period. Nodes with reactive hyperplasia were larger and had heterogeneous enhancement patterns distinctly different from normal nodes. CONCLUSION: Percutaneous CT lymphography effectively depicts the macroscopic intranodal architecture in rabbits.

Animals↗
PubMed1994

Time-lapse quantitative computed tomography lymphography: assessing lymphatic function in vivo.

RATIONALE AND OBJECTIVES: Immobility and massage produce different local limb lymph flow rates. We studied their influence on accumulation of radiopaque nanoparticulates in regional lymph nodes of normal rabbits. METHODS: Quantitative lymphography at 10-min intervals was used to follow the transport of subcutaneous (s.c.) nanoparticulates produced from insoluble esters of diatrizoic acid. In one design, both hindpaws received 0.5 ml of nanoparticulate s.c., and one hindpaw was massaged. In a second design, one hindpaw was injected and massaged while imaging the popliteal, presacral, and paraaortic nodes every 10 min. RESULTS: Gentle massage rapidly increased popliteal node accumulation in comparison with the immobile limb. On the massaged side, mean Hounsfield (HU) units, maximum Hounsfield units, and calculated iodine were significantly greater at 10 min and all subsequent times. In the node transfer experiments, it took 12, 30, and 45 min, respectively, to obtain 100-HU mean attenuation; 200-HU maximum attenuation thresholds were achieved at 20, 47, and 69 min, respectively. CONCLUSION: Quantitative computed tomography lymphography reflects local lymph physiology. Gentle massage of the s.c. injection site is a powerful lymphotropic stimulus.

Analysis of Variance↗
PubMed1994

Nanoparticulate computed tomography contrast agents for blood pool and liver-spleen imaging.

RATIONALE AND OBJECTIVES: We investigated the properties of a group of iodine-containing, insoluble compounds formulated as nanoparticles for use as potential blood pool and liver-spleen contrast agents. METHODS: High-resolution, quantitative computed tomography (CT) was performed prior to and at intervals following the intravenous administration of the contrast agents to rabbits. Time-density characteristics for three organs were evaluated. RESULTS: Excellent enhancement of blood (< or = 232 Hounsfield units [HU]), liver (< or = 263 HU), and spleen (< or = 350 HU) was achieved at the administered dose of 3.0 ml/kg. The composition of the agents influenced the biodistribution, as well as the residence time in blood, and time to peak enhancement in liver. CONCLUSION: Iodinated nanoparticulate compounds are promising CT contrast agents. Development of agents with desirable pharmacokinetic and biodistribution profiles may permit application-specific contrast enhancement.

Animals↗