CN111377968B - Aryl-containing boric acid 99m Tc (III) complex, and medicine box formula and application thereof - Google Patents
Aryl-containing boric acid 99m Tc (III) complex, and medicine box formula and application thereof Download PDFInfo
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Abstract
The invention provides a boric acid containing aryl 99m Tc (III) complex with a molecular formula of 99m TcCl(CDO)(CDOH) 2 B-R. The compound has the advantages of simple preparation, low price, high labeling rate and radiochemical purity, high target-to-non-target ratio, high heart uptake value, long residence time and the like, and can be used as a novel technetium-99 m labeled myocardial perfusion imaging agent in the technical fields of radiopharmaceuticals chemistry and clinical nuclear medicine.
Description
Technical Field
The present invention relates to 99m Tc complex, in particular to an arylboronic acid 99m Tc (III) complex, and a kit formulation and application for preparing the complex.
Background
Cardiovascular disease (CAD) is one of the most serious diseases threatening human health. In China, the morbidity and mortality of CAD are continuously rising. Currently, it is estimated that there are 2.9 million cardiovascular patients nationwide, and in 2012, the published data of "chinese cardiovascular report 2013" shows that: the mortality rate of cardiovascular diseases in 2012 is 255/10 ten thousand. It is estimated that about 350 ten thousand people die annually from cardiovascular disease. Cardiovascular disease accounts for 41.1% of urban resident disease death constitution in 2012, accounts for 38.7% of rural areas, and is higher than tumors and other diseases.
Cardiovascular disease (CAD) is caused by gradual stenosis of the coronary arteries due to atherosclerosis of the coronary arteries. Coronary artery stenosis can lead to reduced coronary blood flow, ischemia of myocardial tissue, insufficient oxygen supply, and myocardial ischemia and even myocardial infarction. Therefore, accurate diagnosis in early stages of CAD formation is of great practical importance for prevention, diagnosis and treatment of CAD diseases.
The non-invasive examination of heart disease by myocardial perfusion imaging starts in the 70 th century, and the great diagnostic value of the myocardial perfusion imaging is widely accepted worldwide and becomes the current diagnosis and efficacy evaluation of coronary heart diseaseOne of the most important imaging methods for price and prognosis. Myocardial perfusion Single Photon Emission Computed Tomography (SPECT) imaging technology is a main method of noninvasive perfusion imaging for coronary heart disease detection in clinic at present, and has important significance in evaluating cardiac function and myocardial perfusion ischemic areas. In patients suffering from cardiovascular diseases, there is basically a situation that myocardial blood flow is reduced, and if the blood flow in a loaded state is significantly lower than that in a resting state, myocardial perfusion defect areas are likely to be caused by myocardial ischemia. If the blood flow under load is comparable to that under resting conditions, the myocardial perfusion defect area is most likely caused by myocardial infarction. The myocardial perfusion imaging medicine is a basic stone of myocardial perfusion imaging technology, and the proportion of the radioactive medicine taken in the myocardium can accurately evaluate the area of myocardial perfusion defects. The accurate measurement of myocardial blood flow has important clinical significance in assessing myocardial ischemia area, severity of cardiovascular disease, myocardial viability, cardiac surgical scheme, postoperative recovery, etc. Coronary Artery Disease (CAD) is the leading cause of both evanescent and permanent damage. Gradual narrowing of the coronary arteries can lead to CAD disease and ultimately myocardial ischemia in the patient. In advanced CAD patients, lower blood flow rates can cause hypoxia of the myocardial tissue and difficulty in maintaining cardiac function, ultimately leading to myocardial infarction. Myocardial Perfusion Imaging (MPI) as a non-invasive means of detecting CAD by means of radiotracers enables assessment of defective areas of cardiac function and blood flow perfusion. For accurate assessment of myocardial blood flow defect areas, uptake of the radiotracer in myocardial tissue must be linear with myocardial blood flow. Accurate measurement of myocardial blood flow is of great clinical importance in identifying ischemic myocardium, assessing CAD disease severity and myocardial viability, and establishing surgical treatment regimens and necessity. Thus, a performance-perfect myocardial perfusion tracer should possess the following characteristics: 1) Has redistribution property; 2) The initial myocardial uptake is high and well-retained, and at high blood flow rates (0-5 mL/min/g) myocardial uptake is still linearly related to blood flow. 99m Tc-Sestamibi is a radioactive tracer commonly used in diagnosis of CAD diseases in nuclear medicine at present, but one major disadvantage is the low first extraction rate, which is the cardiac muscleMyocardial uptake values at blood flow > 2.5mL/min/g lack a linear relationship with local myocardial blood flow. Currently, in all 99m Among the Tc-labeled radiotracers for myocardial perfusion, 99m the first pass rate of Tc-Teboroxine is highest, but the myocardial retention is poor, about 60% of the radioactivity is cleared from the myocardium after 5min post-injection, and when myocardial blood flow reaches 2.5mL/min/g, myocardial uptake values and local blood flow are linear within 5min post-injection, which is detrimental to myocardial viability assessment. These factors limit the clinical use of 99 mTc-teborome. Today it is an urgent task to find a radiotracer with good myocardial retention and biological properties.
Disclosure of Invention
The invention aims to provide an arylboronic acid which has the advantages of simple preparation, low cost, high labeling rate, high radiochemical purity, high target-to-non-target ratio, high heart uptake value, long retention time and the like 99m Tc (III) complexes.
Another object of the present invention is to provide a process for producing the arylboronic acid 99m Kit formulation of Tc (III) complexes.
Another object of the present invention is to provide the arylboronic acid 99m Use of Tc (III) complexes in the preparation of myocardial perfusion imaging agents.
In order to solve the problems, the invention mainly adopts the following technical scheme:
(1) Aryl-containing boric acid 99m Tc (III) complex with a molecular formula of 99m TcCl(CDO)(CDOH) 2 B-R has a structure shown in a general formula (1):
wherein R is the following group:
(2) The arylboronic acid of claim 1 99m Tc (III) complexA compound which is the following compound, 99m Tc-4BOHboroxime：
99m Tc-3BOHboroxime：
99m Tc-2BOHboroxime：
(3) A process for preparing an arylboronic acid of claim 1 or 2 99m A kit formulation of Tc (III) complexes, characterised in that the formulation ingredients comprise 2mg Cyclohexanedioxime (CDOH) 2 ) 2-5 mg of R-substituted boric acid and 50-60 mu g of SnCl 2 ·2H 2 O (preferably 50 mug), 9mg of citric acid, 2mg of Diethyl Triamine Pentaacetic Acid (DTPA), 20-50 mg of sodium chloride, 20-40 mg of gamma-cyclodextrin.
(4) The kit of claim 3, wherein the formulation ingredients comprise 2mg cyclohexanedione dioxime (CDOH 2 ) 1mg of R-substituted boric acid, 50. Mu.g of SnCl 2 ·2H 2 O,9mg of citric acid, 2mg of Diethyl Triamine Pentaacetic Acid (DTPA), 20mg of sodium chloride and 20mg of gamma-cyclodextrin.
(5) The kit of claim 3, wherein the aryl-containing boronic acid is 99m Tc (III) complex is 99m Tc-4BOHboroxime, said formulation containing 2mg Cyclohexanedione Dioxime (CDOH) 2 ) 1.0mg of 4-hydroxymethylphenyl boronic acid, 50 μg of SnCl 2 ·2H 2 O,9mg of citric acid, 2mg of Diethyl Triamine Pentaacetic Acid (DTPA), 20mg of sodium chloride and 20mg of gamma-cyclodextrin.
(6) The kit of claim 3, wherein the aryl-containing boronic acid is 99m Tc (III) complex is 99m Tc-3 BOHbooxime, obtainedThe formulation contained 2.0mg Cyclohexanedione Dioxime (CDOH) 2 ) 1.0mg of 3-hydroxymethylphenylboronic acid, 50. Mu.g of SnCl 2 ·2H 2 O,9.0mg of citric acid, 2.0mg of Diethyl Triamine Pentaacetic Acid (DTPA), 20.0mg of sodium chloride, 40.0mg of gamma-cyclodextrin.
(7) The kit of claim 3, wherein the aryl-containing boronic acid is 99m Tc (III) complex is 99m Tc-2BOHboroxime, the formulation contains 2.0mg Cyclohexanedione Dioxime (CDOH) 2 ) 1.0mg of 2-hydroxymethylphenyl boronic acid, 50 μg of SnCl 2 ·2H 2 O,9.0mg of citric acid, 2.0mg of Diethyl Triamine Pentaacetic Acid (DTPA), 20.0mg of sodium chloride, 40.0mg of gamma-cyclodextrin.
(8) The arylboronic acid of claim 1 or 2 99m Use of Tc (III) complexes in the preparation of myocardial perfusion imaging agents.
ADVANTAGEOUS EFFECTS OF INVENTION
Compared with the existing compounds, the complex of the invention has the following beneficial effects:
1、 99m TcCl(CDO)(CDOH) 2 the radioactive technetium-99 m in the B-R molecule can be used for Single Photon Emission Computed Tomography (SPECT) and is low in cost.
2. Preparation using the kit of the invention 99m TcCl(CDO)(CDOH) 2 The chemical synthesis reagents used in the B-R are all commercial products, have wide sources and are easy to obtain, the preparation of the imaging agent can be completed by simple steps, and the marking rate and the radiochemical purity are high, so that the method is more suitable for clinical application and popularization.
3. According to the invention 99m TcCl(CDO)(CDOH) 2 B-R, which has excellent initial uptake and retention of heart, and has been reported as a myocardial perfusion imaging agent 99m Compared with Tc-Teboroxine, tc-Teboroxine has better biological performance, can be suitable for a clinical imaging scheme with longer time, can be suitable for a common clinical SPECT device, and has more clinical application value.
Drawings
[ FIG. 1 ]]Is a representation of 99m The radioactive HPLC spectrum of Tc-4BOHboroxime (RCP > 95%).
[ FIG. 2 ]]Is a representation of 99m The radioactive HPLC spectrum of Tc-3BOHboroxime (RCP > 95%).
[ FIG. 3 ]]Is a representation of 99m The radioactive HPLC spectrum of Tc-2BOHboroxime (RCP > 95%).
[ FIG. 4 ]]Is a representation of 99m Tc-2BOHboroxime、 99m Tc-3BOHboroxime、 99m Tc-4 BOHborotime and reported 99m SPECT dynamic planar visualization of Tc-Teboroxine in minipigs.
[ FIG. 5 ]]Is a representation of 99m Tc-2BOHboroxime、 99m Tc-3BOHboroxime、 99m Tc-4 BOHborotime and reported 99m Uptake of Tc-Teboroxine in key organs of small pigs average radioactivity count.
[ FIG. 6 ]]Is a representation of 99m Tc-4 BOHbooxime (4 BOH) and 99m SPECT dynamic tomography in normal minipigs for Tc-Teboroxime (TEBO).
Detailed Description
Below to 99m Tc-4BOHboroxime、 99m Tc-3 BOHbooxime 99m Tc-2 BOHborotime is taken as an example to detail the invention by way of example. 1. Preparation of the Compounds
Materials: CDOH (cdOH) 2 (cyclohexanedione oxime), boric acid, snCl 2 ·2H 2 O, citric acid, DTPA (diethylenetriamine pentaacetic acid), gamma-cyclodextrin, 4BOH (4-hydroxymethylphenyl boric acid), 3BOH (3-hydroxymethylphenyl boric acid), 2BOH (2-hydroxymethylphenyl boric acid). All purchased from Sigma/Aldrich. Na (Na) 99m TcO 4 From atomic Gaokou Co., ltd
HPLC apparatus and method: instrument: waters 1525 binary high pressure liquid chromatography system, 2998 full wavelength UV detector, raytest Gabistar radioactivity detector.
Chromatographic column: SUNFIRE C185 μm 4.6X150mm
Flow rate: 1mL/min
Mobile phase: a:10mM ammonium acetate buffer (ph=6.8) B: methanol.
The method comprises the following steps: gradient elution, 0-5min,30% A;5-15min,30-10%
(1)[ 99m Tccl(CDO)(CDOH) 2 B-4BOH]Is prepared from the following steps:
[ 99m TcCl(CDO)(CDOH) 2 B-4BOH]is prepared by a method of medicine box, and contains CDOH 2 2mg,4BOH (4-hydroxymethylphenylboronic acid) 1mg, snCl 2 ·2H 2 Into a penicillin bottle of 50 mug of O,9mg of citric acid, 2mg of DTPA, 20mg of sodium chloride and 50mg of gamma-cyclodextrin 99m TcO 4 - 1.0mL (370-1110 MBq) of the solution was reacted at 100℃for 10min. Then, the mixture was diluted to 3.7MBq/mL with 20% propylene glycol physiological saline. The final label was subjected to HPLC detection without further purification, and the results are shown in FIG. 1.
Route 1: 99m preparation route of Tc-4 BOHbooxime
(2)[ 99m TcCl(CDO)(CDOH) 2 B-3BOH]Is prepared from the following steps:
[ 99m TcCl(CDO)(CDOH) 2 B-3BOH]is prepared by a method of medicine box, and contains CDOH 2 2mg,3BOH (3-hydroxymethylphenylboronic acid) 1mg, snCl 2 ·2H 2 Into a penicillin bottle of 50 mug of O,9mg of citric acid, 2mg of DTPA, 20mg of sodium chloride and 40mg of gamma-cyclodextrin 99m TcO 4 - 1.0mL (370-1110 MBq) of the solution was reacted at 100℃for 10-15min. Then, the mixture was diluted to 3.7MBq/mL with 20% propylene glycol physiological saline. The final label was subjected to HPLC detection without further purification, and the results are shown in FIG. 2. .
Route 2: 99m preparation route of Tc-3 BOHbooxime
Route 3: 99m tc-2 BOHborpimePreparation route
(3)[ 99m TcCl(CDO)(CDOH) 2 B-2BOH]Is prepared from the following steps:
[ 99m TcCl(CDO)(CDOH) 2 B-2BOH]is prepared by a method of medicine box, and contains CDOH 2 2mg,2BOH (2-hydroxymethylphenylboronic acid) 1mg, snCl 2 ·2H 2 Into a penicillin bottle of 50 mug of O,9mg of citric acid, 2mg of DTPA, 20mg of sodium chloride and 40mg of gamma-cyclodextrin 99m TcO 4 - 1.0mL (370-1110 MBq) of the solution was reacted at 100℃for 10-15min. Then diluted to 3.7MBq/mL with 20% propylene glycol physiological saline. The final label was subjected to HPLC detection without further purification, and the results are shown in FIG. 3.
Preparation of injection:
the above-mentioned components are contained 99m The radioactive injection of Tc was passed through a sterile 0.22 μm filter which was rinsed with 0.5mL of a physiological saline solution containing 50% propylene glycol. The resulting filtrate was then diluted to 370-550MBq/mL. The injection dose in the biodistribution experiment was about 1.1MBq/mL, and the injection volume was 0.1 mL/mL. The injected dose in the imaging study was approximately 370MBq/mL, with an injection volume of 0.2-0.5mL.
2. Experimental results
(1) Results of major organ biodistribution in CD-1 mice:
CD-1 mice (n=5) weighing 18-20g were tail vein injected with the required tracer-0.185 MBq and then sacrificed after isoflurane anesthesia at 2, 5, 15, 30 and 60min post injection. The radioactivity counts of organs such as heart, stomach, intestine, kidney, liver, lung, meat, bone, spleen, blood, thyroid were measured using a Perkin Elmer Wizard-2470-counter, and finally the biodistribution data (% ID/g) was calculated.
In the following Table 1, it will be shown that 99m Tc-2BOHboroxime、 99m Tc-3 BOHbooxime 99m % ID/g values at each key organ at 2, 5, 15, 30 and 60min after Tc-4BOHboroxime injection into CD-1 mice.
Table 1. 99m % ID/g value of Tc-2 BOHborotime in each organ of CD-1 mice
Table 2. 99m % ID/g value of Tc-3 BOHborotime in each organ of CD-1 mice
Table 3. 99m % ID/g value of Tc-4 BOHborotime in each organ of CD-1 mice
As described above, the tracers [ are shown in Table 1 99m TcCl(CDO)(CDOH) 2 B-R](R=2BOH, 3BOH and 4BOH in the biological distribution data of major viscera in minipigs. From the above data, it can be confirmed that myocardial uptake at 2 min post injection 99m Tc-3BOHboroxime＞ 99m Tc-2BOHboroxime＞ 99m Tc-4 BOHborpime. Uptake in the liver 99m Tc-3BOHboroxime＞ 99m Tc-2BOHboroxime＞ 99m Tc-4 BOHborpime. Uptake in the lungs 99m Tc-3BOHboroxime＞ 99m Tc-2BOHboroxime≈ 99m Tc-4 BOHborpime. In addition, there was no significant difference in the uptake of the three in the kidneys. It is surprising that, 99m Tc-2BOHboroxime、 99m tc-3 BOHbooxime 99m The heart/liver ratio of Tc-4BOHboroxime is significantly higher than that of the reported tracer 99m Tc-Teboroxine. The introduction of R-substituted boric acid shown in the general formula (1) has obvious influence on the performance of the tracer, and excellent initial heart uptake and retention effects are obtained. Considering the fact that the uptake of the liver and lungs in the living body has a large influence on the cardiac uptake and quantitative analysis and the uptake of other non-target organs is similar, 99m tc-4BOHboroxime has better overall biological properties in mice.
(2) SPECT dynamic planar imaging studies in normal miniature pigs.
With the same miniature pig (30 k)g) Separately injecting tracers as subjects [ 99m TcCl(CDO)(CDOH) 2 B-R](r=me, 2BOH,3BOH and 4 BOH) SPECT/CT dynamic planar imaging studies were performed. When R is Me, it is reported in the prior art 99m Tc-Teboroxine. The experimental animal is anesthetized by intravenous injection of 3% pentobarbital sodium, the dosage is 30mg/kg, and the experimental animal is placed in the supine position of the examination bed after anesthesia. The imaging instrument was SIEMENS ET-CT (Siemens Symbia, germany). Intravenous radio tracer 99m TcCl(CDO)(CDOH) 2 B-R](r=me, 2BOH,3BOH and 4 BOH) (about 370 MBq) and then flushing the injection line with 2mL of physiological saline. The data acquisition and processing scheme comprises the following steps: parallel hole low-energy high-resolution collimator, matrix 128×128, amplification factor 1.45, window width + -20%, energy peak 140keV. The images were then analyzed by 2 experienced nuclear medicine practitioners using Siemens' own software to delineate equally sized regions of interest in the myocardium, liver and lung, obtain the results of the radioactive uptake, correct with the injected dose, and calculate the heart/liver, heart/lung ratio.
For [ 99m TcCl(CDO)(CDOH) 2 B-R]The incorporation of specific R (i.e., 2BOH,3BOH, and 4BOH, and the like) substituted borates as described herein is very effective in improving myocardial uptake, myocardial clearance, and excretion. Initial uptake of myocardium in biological Performance assessment using CD-1 mice as model 99m Tc-3BOHboroxime＞ 99m Tc-2BOHboroxime＞ 99m Tc-4BOHboroxime has great potential to be a new generation of myocardial perfusion imaging agent. Wherein, the liquid crystal display device comprises a liquid crystal display device, 99m the myocardial uptake of Tc-3BOHboroxime is highest, but the hepatopulmonary background, which has a large impact on the heart, is too high, overall, 99m tc-4BOHboroxime has better biological properties in mice.
In small pigs, high excretion rates of the radiotracer in the blood, liver and lung increase the core/background ratio of the tracer, resulting in high quality myocardial SPECT images. In FIGS. 4 and 5, are listed 99m Tc-2BOHboroxime、 99m Tc-3BOHboroxime、 99m Tc-4 BOHborotime and reported 99m Tc-TeboroThe uptake value of xime in key tissues such as heart, liver, lung and the like and the ratio of heart/background. In general terms, the process is carried out, 99m Tc-2BOHboroxime、 99m Tc-3BOHboroxime、 99m tc-4 BOHbooxime blood background 99m Tc-Teboroxine (see FIG. 4) is in proximity; myocardial uptake at 2 min post injection 99m Tc-3BOHboroxime＞ 99m Tc-2BOHboroxime＞ 99m Tc-4 BOHborpime, significantly higher than 99m Tc-Teboroxine (see FIG. 4, FIG. 5). Uptake in the liver 99m Tc-3BOHboroxime＞ 99m Tc-2BOHboroxime＞ 99m Tc-Teboroxime＞ 99m Tc-4 BOHborpime (see FIG. 4, FIG. 5). Uptake in the lungs 99m Tc-3BOHboroxime＞ 99m Tc-2BOHboroxime＞ 99m Tc-4BOHboroxime＞ 99m Tc-Teboroxine. From the above analysis and development results [ 99m TcCl(CDO)(CDOH) 2 B-R](r=2boh, 3BOH and 4 BOH) myocardial uptake 2 to 20 minutes after in vivo injection in minipigs was superior to that reported 99m Tc-Teboroxine, although the liver and lung background is high, the initial uptake of cardiac muscle which benefits from the high tracer of the type, leads to better heart-liver ratio than that of the traditional Chinese medicine 99m Tc-Teboroxine, from these results, can be demonstrated: 99m TcCl(CDO)(CDOH) 2 B-R](r=2boh, 3BOH and 4 BOH) are superior as myocardial perfusion imaging agents 99m Tc-Teboroxine. On the basis of equivalent first extraction rate, the tracer of the invention has good biological performance and wide development prospect. At the position of 99m Tc-2BOHboroxime、 99m Tc-3 BOHbooxime 99m Tc-4 BOHborotime, 99m the myocardial uptake and retention of Tc-3 BOHborotime is best, but the liver and lung background is high to influence the final myocardial development effect, in terms of image quality, at 2-20 minutes after injection, 99m tc-4BOHboroxime is better and these excellent biological properties determine that the invention is a potential SPECT myocardial perfusion imaging agent.
(3) Pig CZT SPECT dynamic tomography study.
The same minipig (30 kg) was used as the subject for separate tracer injections 99m TcCl(CDO)(CDOH) 2 B-R](r=me and 4 BOH) SPECT/CT kinetic scissionLayer development studies. The experimental animals were anesthetized with 3% pentobarbital sodium intravenous injection at a dose of 30mg/kg. After anesthesia, the experimental animal was placed in a supine position on the examination bed, connected to an electrocardiograph to monitor respiration and heart rate, and the imaging instrument was a CZT SPECT instrument (Discovery NM 530c in the united states). Cardiac localization by pre-injection of approximately 37MBq (3 ml volume) of imaging agent from an ear vein catheter followed by "bolus" injection of 370MBq (4 ml volume) respectively 99m Tccl(CDO)(CDOH) 2 B-R](r=me and 4 BOH), the injections were simultaneously acquired dynamically for 15min using list mode. The matrix is 32×32, window width is ±6%, peak 140kev,16 frames/cardiac cycle. After SPECT image acquisition is completed, GE Discovery 640 SPECT/CT is used for acquiring chest CT, and the position of the small pig is kept the same in the 2 image acquisition processes. Reconstruction with SPECT-specific image processing software MyoFlowQ (BCBTI, taiwan, china) followed by analysis of images with ImageJ 1.49 software (national institutes of health) for healthy minipig injection 99m Tc-Teboroxine 99m Tomographic images within 15min after Tc-4 BOHborotime are shown in FIG. 6. 99m Tc-Teboroxine can be quickly absorbed by myocardial tissue after injection, each wall of left ventricle can be clearly developed within 1-9min, and after 9min, the situation of sparse radioactivity appears, which shows that 99m Tc-Teboroxine eluted in small pigs' myocardial tissue and was poorly retained, as can be seen from FIG. 6, the radioactivity tended to decrease gradually after 1min post injection. The liver uptake was also evident within 1-15min after reinjection, and there was no decreasing trend, and it was even stronger than that of the myocardium after 9min after injection, indicating 99m Tc-Teboroxine has a high liver background in the body of small pigs and can affect cardiac imaging later. Compared with 99m Tc-Teboroxime， 99m Tc-4 BOHborotime can quickly absorb peak value in myocardial tissue of small pig and can last for 15min after injection, myocardial contour is always clear and uniformly distributed, and is superior to that of small pig 99m Tc-Teboroxine, and its corresponding liver uptake was also significantly lower 99m Tc-Teboroxine meets the condition of future SPECT blood flow quantification and can give consideration to myocardial perfusion imaging. Thus, the first and second substrates are bonded together, 99m tc-4BOHboroxime as myocardial perfusion imaging agent for evaluating SPECT myocardial blood flow quantification and myocardial perfusion formulaThe face is more advantageous.
Industrial applicability
As is clear from the above results, the arylboronic acid of the present invention 99m Tc (III) complexes with what has been reported so far 99m Tc-Teboroxine has distinct advantages over the other in several respects, among which 99m The biological performance of Tc-4BOHboroxime is optimal, and can be applied to clinic.
Claims (8)
1. Aryl-containing boric acid 99m Tc (III) complex with a molecular formula of 99m TcCl(CDO)(CDOH) 2 B-R has a structure shown in a general formula (1):
；
wherein R is the following group:
。
2. an arylboronic acid of claim 1 for the preparation of 99m Tc (III) complex composition, characterized in that it comprises 2mg of cyclohexanedioxime, 2-5 mg of R-substituted boric acid, 50-60. Mu.g of SnCl 2 ·2H 2 O,9mg of citric acid, 2mg of diethyl triamine pentaacetic acid, 20 to 50mg of sodium chloride and 20 to 40mg of gamma-cyclodextrin.
3. The composition of claim 2, wherein SnCl 2 ·2H 2 The amount of O was 50. Mu.g.
4. The composition of claim 2, wherein the composition comprises 2mg cyclohexanedioxime, 4mg R-substituted boric acid, 50 μg SnCl 2 ·2H 2 O,9mg of citric acid, 2mg of diethyl triamine pentaacetic acid, 20mg of sodium chloride and 20mg of gamma-cyclodextrin.
5. The composition of claim 2, wherein the aryl-containing boric acid 99m Tc (III) complex is 99m Tc-4 BOHborpime containing 2mg cyclohexanedioxime, 2mg 4-hydroxymethylphenyl boric acid, 50. Mu.g SnCl 2 ·2H 2 O,9mg of citric acid, 2mg of diethyl triamine pentaacetic acid, 20mg of sodium chloride and 20mg of gamma-cyclodextrin.
6. The composition of claim 2, wherein the aryl-containing boric acid 99m Tc (III) complex is 99m Tc-3 BOHboroxylme containing 2.0mg cyclohexanedioxime, 4.0mg 3-hydroxymethylphenyl boric acid, 50. Mu.g SnCl 2 ·2H 2 O,9.0mg of citric acid, 2.0mg of diethyl triamine pentaacetic acid, 20.0mg of sodium chloride, 40.0mg of gamma-cyclodextrin.
7. The composition of claim 2, wherein the aryl-containing boric acid 99m Tc (IH) complex is 99m Tc-2 BOHborpime containing 2.0mg cyclohexanedioxime, 4.0mg 2-hydroxymethylphenyl boric acid, 50. Mu.g SnCl 2 ·2H 2 O,9.0mg of citric acid, 2.0mg of diethyl triamine pentaacetic acid, 20.0mg of sodium chloride, 40.0mg of gamma-cyclodextrin.
8. The arylboronic acid of claim 1 comprising 99m Use of Tc (III) complexes in the preparation of myocardial perfusion imaging agents.
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