Aspectos físico-químicos de los contrastes radiológicos iodados y sus posibles reacciones secundarias / Physical and chemical aspects of the iodine radiological contrasts and its possible secondary reactions

El objetivo del presente trabajo es exponer un grupo de compuestos iodados con tres y seis átomos de iodo en su molécula que son derivados del ácido benzoico y son utilizados en Radiología como medios de contraste de gran interés clínico. Se estudian sus constantes físico-químicas y las ventajas que presentan los contrastes no iónicos sobre los iónicos. Se describen también los posibles efectos colaterales indeseables en un pequeño pero importante número de pacientes que pueden producirse por su inyección intravascular (AU)

Intraneoplastic application of metrizamide-containing liposomes: kinetic studies with computed tomography.

Liposomes may serve as drug carriers not only for systemic chemotherapy but also for intraneoplastic drug therapy because they show a sustained drug release. In the present study, the in vivo kinetics of intraneoplastic deposits of large multilamellar vesicles containing metrizamide was followed up in a rat tumor model with computed tomography. The influence of four different lipid compositions on the retardation capacity of large multilamellar liposomes was investigated. By comparing the dynamic data of X-ray attenuation and volume of liposome deposits, a rank order for the in vivo stability of metrizamide containing multilamellar vesicles could be established: the least stable liposomes were made of pure dimyristoyl-phosphatidyl-choline, the most stable type was made of equimolar parts of stearoyl-palmitoyl-phosphatidyl-choline and cholesterol. Of intermediate stability were liposomes made of equimolar parts of dimyristoyl-phosphatidyl-choline and cholesterol, and those made of pure stearoyl-palmitoyl-phosphatidyl-choline. The addition of 50% cholesterol increased the membrane stability of both dimyristoyl-phosphatidyl-choline and stearoyl-palmitoyl-phosphatidyl-choline liposomes. No diffusion of large multilamellar liposomes away from the injection site was observed. The in vivo stability of the liposomes was considerably less than that observed in vitro, suggesting active degradation processes. It is concluded that large, multilamellar liposomes may be suitable carriers for intraneoplastic chemotherapy. The present model is easily adaptable to be transferred into clinical conditions, and may allow direct monitoring of intraneoplastic liposome-mediated chemotherapy in human brain tumors.

In vitro release and depot effect after intratumoral application of metrizamide-containing liposomes.

The drug release and intratumoral residence time of small and large liposomes composed of saturated phospholipids and cholesterol were measured in vitro and in tumor-bearing rats by computed tomography. The in vitro release of metrizamide at 37 degrees C was higher in tissue fluid than in diluted serum and PBS-buffer. The extent of release was 20%/48 h for the 100 nm-liposomes and 10%/48 h for the 480 nm liposomes. The decrease of x-ray contrast after intratumoral application resulted in a half-life of t50 = 0.05 d for metrizamide solution and t50 = 0.42 d for small liposomes. Large liposomes showed a linear decrease in contrast, the half-life being t50 = 15 d. While small liposomes rapidly leave the tumor, large liposomes rest intact in the tumor for about 30 d. Therefore they fulfill a fundamental prerequisite for intratumoral depots of cytostatics with controlled release.

[Adverse reactions and intracranial contrast medium after myelography].

Correlation between adverse reactions and intracranial contrast media after myelography was studied. Myelography was carried out for 12 cases with metrizamide and 14 with iotrolan. In all patients, cranial CT scans were performed 18 approximately 22 hours after myelography. CT attenuation value of subarachnoid cistern was higher than the gray matter in 12 cases and lower in 14 cases. Six cases suffered from adverse reactions, but only 1 case belongs to the higher group. No correlation between adverse reactions and residual amount of contrast medium on CT was recognized.

Absence status epilepticus with computed tomographic brain changes following metrizamide myelography.

Absence status epilepticus following metrizamide myelography was associated with computed tomographic scan evidence of a high concentration of the dye in brain gray matter. We suggest that absence status epilepticus is due to the direct effect of metrizamide on the cortex and that this clinically treatable condition may have escaped diagnosis in previous reports.

Clinical and experimental studies on permeability of tracers in normal spinal cord and syringomyelia.

Delayed CT Myelography (CTM) demonstrated intramedullary cavities in 18 patients, most of which appeared on the 6-hour scan. The attenuation values of the normal spinal cord increased progressively with time, and recorded a peak at 6 hours. The CT numbers of the gray matter of metrizamide were significantly high, as compared with those of iotrol. In the tracer study reported, lanthanum penetrated through the marginal glia to the normal and pathologic spinal cord. Reaction products of horseradish peroxidase (HRP) were mainly in the extracellular space of the normal spinal cord. The pathologic spinal cord, however, allowed the passage of HRP into the parenchyma through the extracellular space of the marginal glia. Consequently, the extracellular space of the spinal cord surface constitutes a pathway for cerebrospinal fluid solutes. Either metrizamide or iotrol thus diffuses into the spinal cord from the subarachnoid space.

[CT kinetics of intratumor liposome deposits]. / CT-Kinetik intratumoraler Liposomendepots.

CT follow-up studies of liposome-entrapped metrizamide after intraneoplastic injection into neurogenic s.c. rat tumors were performed. By closely resembling clinical examination conditions, the experimental design has proven suitable in determining the in vivo kinetics of these interstitial liposome deposits. When compared to free metrizamide which may be considered an analogue of water-soluble chemotherapeutics, the encapsulation of metrizamide in liposomes resulted in a retarded decline of the contrast enhancement. Diffusion of liposomes could not be detected and the X-ray attenuation values measured within the liposome deposits continuously decreased with time for both types of liposomes. In the case of multilamellar vesicles, this significantly corresponded to a zero order kinetics with a mean halflife of 300 h. An initial increment in the X-ray attenuation of the liposome deposits might be due to the interstitial absorption of the water component of the liposome-dispersion. Because of the pronounced retardation effect of multilamellar liposomes resulting in a 140-fold prolongation of the interstitial retention time of metrizamide and due to their release kinetics these vesicles may be an appropriate carrier system for a local interstitial chemotherapy modality. Small unilamellar vesicles having an interstitial half-life of 14 h may be used as a faster component of a composed therapy system.

Computed tomography, magnetic resonance imaging, and pathologic observations of the effects of intrathecal metrizamide and iohexol on the canine central nervous system.

A two-group crossover design experiment was used in eight dogs to compare the effects of intrathecally injected (0.25 mL/kg, 180 mg I/mL) metrizamide and iohexol. Additional acute observations were made in four of the dogs following a high dose (0.45 mL/kg of 300 mg I/mL) of each agent. In computed tomographic observations, there was progressive passage of each contrast medium across the interface between the cerebrospinal fluid and the brain, and statistically identical levels of each contrast medium were present in the cerebral gyri. There was a similar passage of contrast medium across the interface between the cerebrospinal fluid and the spinal cord. The rate of passage of each agent into the brain parenchyma suggested their active transport rather than a simple diffusion. In both T2-weighted magnetic resonance imaging and histopathologic studies, there was no evidence of cerebral edema following either high or low doses of each agent. In T1-weighted images made following the intravenous injection of gadolinium-DTPA (0.1 mmol/kg), the blood-brain barrier was intact.

Metrizamide brain penetrance.

The normal cerebrospinal fluid flow as monitored by serial CT cisternography with metrizamide (Amipaque) is described in 25 individuals. Preliminary gross autoradiography using 131I-labelled metrizamide concur with these CT cisternographic findings indicating that intrathecally introduced metrizamide penetrates the brain substance. Adverse reactions are most prominent during the periods of maximum brain penetration and include headache, nausea, perceptual aberrations, and EEG alterations. The value and diagnostic applications of cerebral and cerebellar penetration of metrizamide are also discussed.

Computer tomography of the spinal canal using metrizamide.

Eleven patients have been examined by whole body CT employing the EMI CT 5000 following lumbar injection of 10 ml of metrizamide (Amipaque) 170 mg I/ml. The distribution, flow and dilution of the contrast medium have been investigated. The results suggest that whilst metrizamide is necessary in the spinal canal to demonstrate the neural axis and pathologic processes affecting it, it appears to enter the extracellular space of the spinal cord during the first hour and achieves an equilibrium in the subarachnoid space and spinal cord from 3 to 6 hours. The medium may concentrate in a second compartment, possibly intracellular, from 3 to 6 hours. The effect of spectral filtering by metrizamide on the attenuation values of the spinal cord has been modelled and shown not to be significant at the anticipated dilution of the medium in the cerebrospinal fluid space and the spinal canal.

Metrizamide enhancement of cerebrospinal fluid for computer tomography.

Enhancement of CT attenuation values of the CSF cisterns by the lumbar injection of metrizamide has been shown to be of value in demonstrating the anatomy of the cisterns. Tumors involving the cisterns, such as acoustic neurinomas and pituitary adenomas, are clearly defined. Coronal scanning was superior to horizontal views in many cases.

Computer tomography and subarachnoid metrizamide for evaluation of cerebrospinal fluid flow.

Twenty-one patients were examined with computer tomography following subarachnoid injection of metrizamide (Amipaque). Five were evaluated because of dementia or possible obstructive hydrocephalus. The remainder were referred for lumbar or cervical myelography and served as controls. Concentration and distribution of the contrast medium within the cranial subarachnoid space and ventricular system depend upon a composite of the physical properties of the contrast medium, patient positioning and activity and CSF physiology.