DE2817336C2 - X-ray contrast media and a diagnostic agent containing the same - Google Patents

Description

example 1

Preparation of the injection solution:

6 g of DIG was dissolved in physiological saline solution and 6 ml of an injection solution (concentration 100%) received.

Preparation of an experimental animal

An angiographic catheter was taken into the femoral artery of a dog weighing 7 kg

Nembutal anesthesia is inserted and the tip of the catheter is set at the entrance of the renal artery Dog was supine on the X-ray table and serial radiograms of the kidney were performed immediately after the injection of 5.5 g / 5.5 ml (100% Solution) performed by DIG for 10 to 20 minutes

54 ml of 80% conraxin were used as a control Since the iodine molecule concentration of DIG is 40% and that of Conraxin is 62%, the administered is Dosage of iodine 5.5 g · 0.4: 4.4 g · 0.62, i.e. H. 2.2 g: 2.73 g are practically the same.

By comparing the images taken immediately after the injection of the two above contrast media X-rays showed practically the same visualization, but DIG showed a clearer renal shadow, which lasted more than 10 minutes. This is likely due to the slower excretion of DIG from the kidney Contrast to that of Conraxin.

Example 2

Highlighted connection:

¹³¹ I-DIG
Laboratory animal:

Rabbit weighing 1.2 kg
Injection site:

Ear vein
Detector:

Scinti camera

Experimental procedure

The rabbit was secured in the supine position under the scinti camera. Successive brain, heart, liver and kidney mapping were performed during and after injection of 100 μα / ml of labeled ¹³¹ I-DIG. The values were saved and later analyzed to obtain the time-activity curve for each organ. These curves were subjected to analysis for glycolytic activity.

Example 3

Patient:

64 year old man
Injection site:

Right cubital vein
Dosage of the injection:

30 μα / ml of labeled DIG
Detector:

4 scintillation counters.

The change in ¹³¹¹ radioactivity at selected sites, namely the brain, heart, liver and urinary bladder, was recorded continuously during and after the injection for 40 minutes. The recorded time-activity curves over the above selected sites were specific for each organ. The maximum activity of ¹³¹ I was in the range liver>heart> brain in decreasing order. The excretion to the bladder was visible from 8 min onwards, showing a rapid increase which reached 80% of the administered dose within 40 min. These time activity curves were subjected to the analysis of the glucose metabolism.

Example 4

Highlighted connection:

'251-DIG (5 μΟ / rat)
¹⁴ C-DIG (2 μα / mouse)

¹⁴ C-glucose (2 μα / mouse)
Laboratory animals:

male SD rat weighing 250 g

or

ίο male ICR mouse weighing 25 g
Administration method:

intravenous or intraperitoneal injection.

Experimental procedure

After administration of these labeled compounds macro autographs have been carried out, the animals were frozen over time and thin sections were at - 20 ⁰ C cut with a microtome. The cut sections were freeze-dried, placed in contact with special films for macroautoradiography in a dark room for 3 to 4 weeks, developed and fixed
With regard to the metabolism and the conversion process within the body of the mouse of ¹²⁵ I-DIG and ¹⁴ C-DIG, the process of absorption, distribution and metabolism within the body was practically identical to that of ⁴ C-glucose in the controls, except the brain.

Example 5

Link:

DIG
Laboratory animal:

Dog weighing 10 kg, anesthetized.
Administration site:

Cerebral ventricle and subarachnoid space.
Visualization of the cerebral vessels, ventricles and the subarachnoid space of the dog and its physiological effect.

This connection was in the cerebral arteries, ventricles, and subarachnoid space of 10 males Injected dogs weighing 10 to 20 kg and their effect as a contrast agent was continuously on 16 mm film and recorded simultaneously electroencephalography and electrocardiography recorded the physiological effects to observe. 8 ml of a 60% aqueous solution of DIG was injected into the cerebral artery and X-ray angiograms were sequentially taken immediately after injection. It became very clear cerebroangiograms as obtained in the control using 10 ml of 60% conraxin.

Using a cannula inserted into the occipital foramen of the anesthetized dog, 1 ml a 50% aqueous solution of DIG is injected into the subarachnoid space. Thereby found a very clear visualization the base of the skull, the brain stem and the secretion of mucus about 30 seconds the injection. Then 1 ml of a 50% aqueous solution of DIG was placed in the cerebral ventricles injected through puncture of the parietal area. The cerebral ventricles could be made clearly visible. It has been shown with these experiments that this compound is rapidly released from the injected sites after a few Minutes disappears.

The recorded electroencephalograms, electrocardiograms and the sensed potential of the brain stem, concurrent with the foregoing Experiments made could show no physiological change at all.

The listening petential showed a wave pattern consisting of 5 peaks in normal dogs duration. In dogs with even minor brain stem damage, this wave pattern was disrupted and one of the 5 peaks disappeared. No effect at all on the wave pattern was found This shows that DIG is a very safe contrast agent for use in diagnosing the central nervous system

In view of the above examples, absorption, distribution and metabolism are these Compound (DIG) within the body practically identical to that of glucose. So can this connection to determine the rate of absorption, distribution, metabolism and excretion be used within the body by external counting. It differs from glucose only in that it is easily excreted in the urine without reabsorption in the kidney.

With regard to the use of DIG as a contrast medium, it is very safe and valuable for visualization of cerebral vessels, ventricles and the subarachnoid space. This proves that DIG is a very safe contrast agent that is also widely used in general angiography can be used.

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Claims (2)

Patent claims: 1. X-ray contrast medium containing 3'-deoxy-3-iodo-glucose. 2. Diagnostic agent containing a radioactive iodine labeled 3'-deoxy-3-iodo-glucose. The invention relates to an X-ray contrast medium and to a diagnostic device containing the same Agent that is valuable in radiology and nuclear medicine. Angiography is an important one in radiology diagnostic procedure used in daily clinical practice. A number of commercially available Contrast media is sometimes toxic and as a result cannot be used with certainty on a daily basis will. In nuclear medicine there are only a few radiodiagnostic agents that monitor metabolic activity of glucose. According to the invention, an X-ray contrast medium containing 3'-deoxy-3-iodo-glucose is provided which is regarded as a substitute for glucose, which is actively converted in the body as an endogenous substrate in the metabolism will. Thus, if this compound is labeled with radioactive nuclei, it can be used to determine the velocity absorption, distribution, metabolism and excretion within the body use by external counting. The connection can also be used with security for universal X-ray contrast media use. The invention also relates to a diagnostic agent which contains a 3'-deoxy labeled with radioactive iodine Contains 3-iodine glucose. This highly water-soluble compound contains 40% iodine in the molecule and shows a high X-ray absorption effect. Since the value of the LDs ₀ of DIG is above 10 g / kg body weight, no side effects could be observed in the cases examined. The radioactive agent containing radioactive iodine-labeled 3'-deoxy-3-iodo-glucose is described below referred to as marked DIG. In this connection the iodine is in position 3 by radioactive Iodine replaced. The movement of this marked compound in the bloodstream can be detected externally with radiation detectors and determination tools are tracked. This compound can be viewed as a substitute for glucose, which is active in the body as an endogenous substrate is involved in the metabolism. By counting the radioactivity across various organs and tissues from the outside, the absorption, the distribution, the burning and retention rates can be analyzed individually across organs and tissues. For example, DIG can be made in the following ways: The starting 3'-deoxy-3-hydrazino-1,2: 5,6rdiisopropylidene-D-allofuranose is treated with iodine or radioactive iodine to form 3'-deoxy-3-iodo-1,2: 5,6-diisopropylidene-D -glucofuranose and then the protective residue is removed either by cation exchange resins or hydrolysis and the 3'-deoxy-3-iodo-glucose is obtained. Examples of radioactive iodine are ^'23 I,' ²⁴ 1, ¹² M, ¹²⁶ 1, ¹²⁸ 1, ¹² '1, ¹³⁰ 1, ¹³¹ 1, ¹³² I and ¹³³ I. For example, ¹³¹ I can be commercially available as sodium iodide or without Addition of a weakly alkaline solution can be obtained. This is commercially available carrier-free state with a content of 0.8 ■ 10- ⁹ g iodine per 1 mCi. Of the above radioactive iodine materials, ¹²³ 1, ¹²⁵ I and ¹³¹ I are preferred in view of half-life, energy and productivity. An example of the manufacturing method follows ίο 20 mCi of radioactive iodine or radioactive sodium iodide and 276 mg of ¹²⁷ I-sodium iodide (cold iodine) were placed in the bottom of a sealed tube and by lowering the temperature to -70 ° C, the pressure inside the tube was reduced 50 mg of manganese dioxide and 0.110 ml of 98% sulfuric acid are introduced into the sealed tube from one end and then heated.This converts the molecular iodine into gaseous iodine in the bottom of the other end of the sealed tube, which had previously been cooled by a freezing mixture 300 mg of 3'-deoxy-3-hydrazino-1,2: 5,6-diisopropylidene-D-allofuranose and 120 mg of N-methylmorpholine, dissolved in 1.5 ml of chloroform, were introduced. The above gas shaped iodine was gradually diffused into it. The chloroform was in the liquid state (-6O ⁰ C) and was stirred at a suitable speed. Diisopropylidene-D-allofuranose removed as far as possible from the chloroform layer. Using cation exchange resins or by hydrolysis and subsequent application of silica gel and activated carbon, toxic by-products were removed and finally the 3'-deoxy-3-iodo-glucose was labeled with iodine can be obtained in good yield without radioisotopic effect (yield about 50%). In order to remove all pathogenic bacteria from the purified compound, 10 mg of the same were added Compound dissolved in 2 ml of methanol and evaporated. The solid finally obtained was in 2 ml of a aseptic physiological saline solution and passed through a millipore filter. That connection aqueous solution containing can be injected or administered orally. By choosing where to inject individual organs and tissues can be examined visually or for the glycolytic metabolism to be studied. When administered orally, the function of the digestive tract can be studied. The X-ray contrast media according to the invention can be in the form of an aqueous solution for injection into the intraspinal, intraventricular and intrasubarachinoidial spaces are present. The X-ray contrast media can also be in the form of an injection solution for the liver, Kidney, salivary tract, pancreatic tract, and other arteries or veins.