iothalamate-meglumine and Brain-Neoplasms

We present a quantitative method for determining a blood-to-tissue influx constant (K1), a tissue-to-blood efflux constant (k2), and tissue plasma vascular space (Vp) that uses a computed tomographic (CT) scanner to make tissue and plasma measurements of the concentration of an iodinated compound. Meglumine iothalamate was infused intravenously over time periods of 0.5-5 min, up to 49 CT scans were obtained at one brain level, and arterial plasma was sampled over a 30- to 40-min period. K1, k2, and Vp were calculated for each voxel of the 320 x 320 matrix, using a two-compartment pharmacokinetic model and nonlinear least-squares regression. The method was used in dogs with avian sarcoma virus-induced brain tumors. As many as four studies on different days were done in the same animal. In tumor-free cortex, K1 of meglumine iothalamate was 2.4 +/- 1.7 microliter g-1 min-1 (mean +/- SD) and Vp was 3.4 +/- 0.5 ml 100 g-1. Mean whole-brain tumor K1 values ranged from 3.3 to 97.9 microliters g-1 min-1; k2 ranged from 0.032 to 0.27 min-1; and Vp ranged from 1.1 to 11.4 ml 100 g-1. These values were reproducible in serial experiments in single animals. Independent verification of K1 values was obtained with quantitative autoradiographic measurements of alpha-aminoisobutyric acid, which has similar physicochemical properties to meglumine iothalamate. The CT methodology is capable of demonstrating regional variation of transcapillary transport in brain tumors and may be of value in the study of human brain tumors.

Topics: Aminoisobutyric Acids; Animals; Autoradiography; Avian Sarcoma Viruses; Biological Transport; Brain; Brain Neoplasms; Capillaries; Dogs; Humans; Infant, Newborn; Iothalamate Meglumine; Sarcoma; Tomography, X-Ray Computed

The rate at which water-soluble chemotherapeutic drugs enter brain tumors can be extremely variable. The ability to measure or predict the rate of drug entry may have an important role in treatment. We have developed a method that uses information from contrast-enhanced computed tomographic scans to measure quantitatively the rate of transcapillary transport of iodinated compounds in brain tumors. In a group of 10 patients with brain tumors, we obtained serial measurements of tissue (Am) and arterial plasma (Cp) iodine concentration from timed computed tomographic scans done over 30 minutes, after intravenous infusion of meglumine iothalamate (Conray-60). These measurements were analyzed with a two-compartment pharmacokinetic model and nonlinear least-squares regression methods to obtain K1, a blood-to-tissue transfer constant; k2, a tissue-to-blood rate constant; and Vp, tissue plasma vascular volume. Images of K1, k2, and Vp were reconstructed after calculating these values for each 0.8 x 0.8 x 5-mm volume element of the original data. Mean whole tumor K1 values varied from 2.0 mu 1 gm-1 min-1 in a thalamic astrocytoma to 33.9 mu 1 gm-1 min-1 in a glioblastoma multiforme. The value of k2 varied from 0.034 to 0.108 min-1, and Vp varied from 2.4 to 7.9 ml 100 gm-1. In tumor-free brain, the K1 of meglumine iothalamate was 2.9 mu 1 gm-1 min-1; k2 was 0.058 min-1; and Vp was 2.1 ml 100 gm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Autoradiography; Biological Transport; Brain Neoplasms; Capillary Permeability; Female; Humans; Iothalamate Meglumine; Male; Middle Aged; Tomography, X-Ray Computed

Whether hyperosmotic blood-brain barrier (BBB) disruption is a technique that can be used to increase permeability of brain-tumor capillaries and thereby transiently increase drug delivery to the brain tumor is controversial. Nine virally induced brain tumors were studied in seven dogs, before and after hyperosmotic BBB disruption with 1.4 osmolar mannitol. Each dog was studied with computerized tomography (CT) after administration of the water-soluble tracer meglumine iothalamate. Each study lasted 30 minutes. A baseline CT scan and 35 to 40 additional CT scans were obtained to provide a time-related measurement of the amount of meglumine iothalamate in tissue (Am(t], and 30 plasma samples were collected to provide the time-related measurement of meglumine iothalamate in plasma (Cp(t]. The data were analyzed by three different methods: 1) a two-compartment model and nonlinear curve fitting were used to calculate K1 (blood-to-tissue or influx constant), k2 (tissue-to-blood or efflux constant), and Vp (plasma vascular space); 2) K1 values were calculated with a two-compartment model, assuming no efflux, at the time point for each CT scan; and 3) a "tissue advantage ratio" was calculated that expressed the ratio of tissue uptake of meglumine iothalamate at each time point, comparing values before and after BBB disruption. Regardless of which method of data analysis was used, there was a marked and significant increase in transcapillary transport of meglumine iothalamate to tumor-free brain regions, while there was only a small, transient, and insignificant increase to the brain tumors. Although there were often marked increases in delivery to cortex in the same hemisphere as the tumors, there was no significant increase to brain immediately surrounding the tumors, perhaps due to altered circulatory dynamics in this region. These data raise serious questions as to the wisdom of using this technique to increase drug delivery to brain tumors in patients and strongly support the continued study of this technique in experimental brain tumors before it is used in patients.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Neoplasms; Capillary Permeability; Dogs; Iothalamate Meglumine; Mannitol; Models, Cardiovascular; Osmolar Concentration

Topics: Animals; Blood-Brain Barrier; Brain Neoplasms; Capillary Permeability; Dogs; Iothalamate Meglumine; Mannitol; Rats

The effect of radiographic contrast agents on the central nervous system was evaluated by measurement of serum creatine kinase B-subunit (CKB) levels with use of radioimmunoassay in 58 patients who underwent computed tomographic (CT) scanning and 46 patients who underwent cerebral angiography for evaluation of cerebrovascular diseases, brain tumors, and other neurologic disorders. In 11 patients (10.6%), the CKB increased to abnormally high levels within 4 hours after the radiographic procedures, and the median value after 30 minutes was significantly higher than the corresponding precontrast value (P less than 0.01). Eight of the 11 patients had recent ischemic cerebrovascular diseases, and 7 of the 11 had undergone CT scanning. On the basis of the information available in the literature, elevation of the serum CKB levels may be interpreted as reflecting breakdown of the blood-brain barrier and neural damage. Intravascularly administered radiographic media are generally safe, but the results of the current investigation suggested the potential for detrimental effects, particularly in patients with recent cerebrovascular diseases.

Topics: Brain; Brain Neoplasms; Cerebral Angiography; Cerebrovascular Disorders; Contrast Media; Creatine Kinase; Diatrizoate Meglumine; Humans; Iothalamate Meglumine; Isoenzymes; Tomography, X-Ray Computed

The nonionic contrast agent iohexol was compared with the ionic agent iothalamate for contrast enhancement of brain tumors and radiation brain damage in dogs. Tissue enhancement during infusion of contrast and 5, 10, 15 and 30 min later was measured using quantitative computed tomography. Blood iodine was measured using x-ray fluorescence. Peak contrast enhancement occurred during infusion in tumors and after 5 min in irradiated normal brain for both contrast agents. Absolute uptake of contrast in each lesion was the same for both agents when normalized to total grams of iodine administered. Blood iodine levels were slightly but not significantly higher using iohexol. The reduced osmotic load and similar contrast enhancement of lesions suggest that the nonionic contrast medium iohexol may be a useful agent for routine CT of the brain.

Topics: Animals; Brain; Brain Neoplasms; Dogs; Ependymoma; Iodine Radioisotopes; Iodobenzoates; Iohexol; Iothalamate Meglumine; Iothalamic Acid; Male; Meningeal Neoplasms; Meningioma; Radiation Injuries, Experimental; Tomography, X-Ray Computed; Triiodobenzoic Acids

Kinetics of an iodinated contrast medium were evaluated quantitatively as a function of time up to one hour after intravenous infusion in the brains of dogs with experimentally induced radiation damage and dogs with spontaneous brain tumor. Radiation damage was characterized by an increase in iodine accumulation soon after the infusion, while tumor concentration of iodine either showed no change or decreased with time. These results suggest that contrast kinetic studies may be useful in differentiating radiation damage to normal brain tissue from a malignant brain tumor.

Topics: Animals; Brain; Brain Diseases; Brain Neoplasms; Diagnosis, Differential; Dogs; Iothalamate Meglumine; Kinetics; Radiation Injuries, Experimental; Tomography, X-Ray Computed

Rapid Sequence Tomography is shown to be a valid instrument to study the local distribution of more or less vascularized brain structures. Functional states as hypo- or hyperperfusion become clearly visible. RSCT permits a clear differentiation between intra- and extravascular contrast enhancement and offers an excellent insight into the angioarchitecture and quality of cerebral lesions.

Topics: Brain Neoplasms; Cerebrovascular Circulation; Cerebrovascular Disorders; Humans; Intracranial Arteriovenous Malformations; Iothalamate Meglumine; Tomography, X-Ray Computed

Results of initial clinical trials of brain tumor chemotherapy after osmotic blood-brain barrier disruption are promising. In general, the procedure is well tolerated. The major complication has been seizures. In this report, data are presented which indicate that the etiology of these seizures is related to the use of contrast agent (meglumine iothalamate) to monitor barrier modification. A series of 19 patients underwent a total of 85 barrier modification procedures. Documentation of barrier disruption was monitored by contrast-enhanced computed tomographic (CT) scanning, radionuclide brain scanning, or a combination of both techniques. In 56 procedures (19 patients) monitored by enhanced CT, seizures occurred a total of 10 times in eight patients. Twenty-three barrier modification procedures (in nine of these 19 patients) documented by nuclear brain scans alone, however, resulted in only one focal motor seizure in each of two patients. In eight of the 19 patients who had seizures after barrier disruption and enhanced CT scan, four subsequently had repeat procedures monitored by radionuclide scan alone. In only one of these patients was further seizure activity noted; a single focal motor seizure was observed. Clearly, the radionuclide brain scan does not have the sensitivity and spatial resolution of enhanced CT, but at present it appears safer to monitor barrier modification by this method and to follow tumor growth between barrier modifications by enhanced CT. Four illustrative cases showing methods, problems, and promising results are presented.

Topics: Adult; Blood-Brain Barrier; Brain; Brain Neoplasms; Carotid Artery, Internal; Child; Drug Therapy, Combination; Female; Humans; Iothalamate Meglumine; Male; Mannitol; Methotrexate; Middle Aged; Osmosis; Pentetic Acid; Radionuclide Imaging; Seizures; Technetium; Technetium Tc 99m Pentetate; Tomography, X-Ray Computed

Topics: Adolescent; Adult; Air; Brain Neoplasms; Cerebral Ventriculography; Child; Contrast Media; Female; Humans; Iothalamate Meglumine; Male; Middle Aged

Five hundred and fifty-three patients with intracranial metastases were analysed, before and after the availability of CT scanning, from three neurosurgical centres. A further analysis of 318 patients, who had a total excision carried out, was made from the six groups (i.e. posterior fossa or craniotomy in each centre) before and after CT scanning was available. A statistically significant reduction in the excision rate occurred in one group after the CT scan was available, and the very small number of patients who survived for more than 12 months was not significantly increased in the groups who had a CT scan carried out. Median survival in the various groups, whether analysed on a unit basis or with all three units combined, was not only poor (two to five months) but was not significantly better in the groups investigated with CT scanning. It would therefore appear that the use of the CT scan has not enabled a more careful selection of patients suitable for excision to take place or improved the median survival. Thus, by implication, and from the evidence of the literature, a more intensive preoperative investigation should be considered in order to exclude possible extracranial metastases and appraise the place of cranial irradiation.

Topics: Brain Neoplasms; Cranial Fossa, Posterior; Female; Humans; Iothalamate Meglumine; Male; Tomography, X-Ray Computed

Disorders of the free passage of the C.S.F. through the Sylvian aqueduct are among the common causes of intracranial hypertension. After the partial or complete obstruction of the aqueduct, the intracranial hypertension may be produced by three different mechanisms - a) by hypertensive hydrocephalus of the third and lateral ventricles, b) by the combination of hydrocephalus and the space-occupying lesion or c) by the acute obstruction of the aqueduct with acute dilatation of the third and lateral ventricles. The supratentorial hypertension may be, in some cases, transferred to the posterior fossa via the incisura tentorii. For many years, neurosurgeons have been trying to restore the free passage of C.S.F by different surgical techniques which could make possible free outflow of supratentorial hypertension. The number of procedures suggested has proved the importance of the obstruction of the Sylvian aqueduct and difficulties in its treatment (5, 6, 14, 15, 16, 17, 18, 19). Since 1972, the selective ventriculography of the third and fourth ventricles with Conray 60 (1, 2, 3, 4, 7, 8, 9, 10, 11, 12, 13, 20, 21) was performed by the author in 1005 patients and pathological findings were proved in 602. Our of 602 patients with pathological findings, the aqueductal stenosis was proved in 39 and complete obstruction of aqueduct in 168 patients, i.e. in 28 per cent of all pathological findings. The new techniques of interventriculostomy (third to fourth ventricle shunt) using Seldinger's technique is described, presented and documented by x-ray pictures. This technique has been used on 5 patients successfully treated upto now.

Topics: Brain Neoplasms; Brain Stem; Cerebral Aqueduct; Cerebral Ventriculography; Dilatation; Humans; Hydrocephalus; Iothalamate Meglumine

Enhanced computerized tomography (CT) is a noninvasive means of monitoring blood-brain barrier (BBB) disruption. In the present study this technique was used to monitor the degree, distribution, extent, and reversibility of osmotic BBB disruption. With a canine model, the timing of administration of iodinated contrast agent was shown to be crucial to optimize enhancement by CT of the disrupted BBB. Meglumine iothalamate given intravenously resulted in excellent enhancement on CT scan. Intracarotid infusion of this contrast agent was less satisfactory. Under similar conditions, enhancement due to metrizamide was less marked and more transient than that observed with meglumine iothalamate. Systemically administered methotrexate after osmotic BBB disruption resulted in increased brain levels in areas that closely correlated with CT scan enhancement. These results suggest that the CT scan provides an excellent noninvasive monitor of both BBB disruption and the delivery of chemotherapeutic agents to the brain. (Neurosurgery 6: 49--56, 1980)

Topics: Animals; Blood-Brain Barrier; Brain Chemistry; Brain Neoplasms; Dogs; Evans Blue; Hypertonic Solutions; Iothalamate Meglumine; Mannitol; Methotrexate; Metrizamide; Radiographic Image Enhancement; Staining and Labeling; Tomography, X-Ray Computed; Water-Electrolyte Imbalance

Topics: Adult; Aged; Brain Neoplasms; Cerebral Infarction; Contrast Media; Diagnosis, Differential; Female; Humans; Iothalamate Meglumine; Male; Middle Aged; Radiographic Image Enhancement; Time Factors; Tomography, X-Ray Computed

Topics: Adolescent; Adult; Brain Neoplasms; Cerebral Ventriculography; Child; Child, Preschool; Female; Humans; Iothalamate Meglumine; Male; Middle Aged

Topics: Brain Neoplasms; Cerebral Ventriculography; Cranial Fossa, Posterior; Humans; Iothalamate Meglumine

Topics: Adolescent; Adult; Brain Diseases; Brain Neoplasms; Cerebral Aqueduct; Cerebral Ventriculography; Child; Child, Preschool; Female; Hallucinations; Humans; Infant; Iothalamate Meglumine; Male; Middle Aged; Pinealoma

Various contrast agents with either sodium or meglumine cations and iothalamate and diatrizoate anions are compared in a series of patients with malignant gliomas. There is no difference in the ability of these agents to enhance tumors in cranial computed tomography.

Topics: Brain; Brain Neoplasms; Diatrizoate; Diatrizoate Meglumine; Glioma; Humans; Iothalamate Meglumine; Tomography, X-Ray Computed

The temporal relationship of blood iodine levels to tumor enhancement in cranial computed tomography was studied in a series of patients. Both the bolus and biphasic techniques were evaluated. Peak tumor intensity may not develop immediately, but may be more pronounced on a 20-minute scan. The low-density centers seen in malignant gliomas show delayed enhancement. These low-density centers represent a second compartment which equilibrates with the intravascular and interstitial contrast material at a much slower rate. Patients with malignant gliomas can be scanned up to one hour following contrast injection without significant loss of information.

Topics: Blood-Brain Barrier; Brain Neoplasms; Contrast Media; Glioma; Humans; Injections, Intravenous; Iodine; Iothalamate Meglumine; Permeability; Radiographic Image Enhancement; Tomography, X-Ray Computed

Difficulties still remain in the routine radiologic examination of the lateral recesses of the fourth ventricle. Ventriculography with the direct introduction of water-soluble contrast medium into the third ventricle has improved the results. The normal anatomic and radiologic appearances and pathologic changes of the lateral recesses are discussed.

Topics: Brain Neoplasms; Cerebral Ventriculography; Contrast Media; Humans; Hydrocephalus; Iothalamate Meglumine

After the first report on ventriculography with a water-soluble contrast medium, Conray, by Campbell et al., many authors reported complications such as convulsion which are attributable to the irritating effect of this agent. On the other hand its value has been appriciated. Recently Gonsette recommended a new water-soluble contrast medium, meglumine iocarnate (Dimer-X), for ventriculography and reported that this new agent is less epileptogenic and less harmful. Because of these advantages, they have been performing ventriculography routinely with Dimer-X and recognized its usefulness. The only noticeable complication has been the transient elevation of body temperature in almost a half of the series. As far as our experience goes there is no case of convulsive seizure as complication. As compared to gas ventriculography, the fine details of dimension and configuration of the ventricles are far more beautifully delineated with the water-soluble contrast media.

Topics: Adult; Brain Neoplasms; Cerebellar Neoplasms; Cerebral Ventricle Neoplasms; Cerebral Ventriculography; Child; Child, Preschool; Craniopharyngioma; Ependymoma; Female; Humans; Infant; Iothalamate Meglumine; Iothalamic Acid; Male; Pinealoma; Teratoma

Topics: Brain Diseases; Brain Neoplasms; Cerebral Ventriculography; Contrast Media; Drug Evaluation; Humans; Iothalamate Meglumine; Solubility; Water