Novel bone seeking <99m>Tc complex, preparation thereof and application thereof

A 99mtc, osteophilic technology, applied in the field of radiopharmaceuticals and nuclear medicine, to achieve low tissue uptake, high target/non-target ratio, and excellent performance

Active Publication Date: 2012-04-25
BEIJING NORMAL UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the late 1960s, the first generation of bisphosphonates appeared, such as etidronate disodium (Etidronte), clodronate disodium (Clodronate), etc., which have weak bone resorption inhibitory effects
The second generation of bisphosphonates, such as Pamidronate, has a higher ability to inhibit bone resorption than etidronate, but it has more side effects on the gastrointestinal tract
Currently, 99mTc-labeled NMBBDP complexes have not been reported at home and abroad

Method used

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  • Novel bone seeking &lt;99m&gt;Tc complex, preparation thereof and application thereof
  • Novel bone seeking &lt;99m&gt;Tc complex, preparation thereof and application thereof
  • Novel bone seeking &lt;99m&gt;Tc complex, preparation thereof and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Embodiment 1 wet preparation 99m Tc-labeled ligand is an osteophilic complex of NMBBDP

[0046] 1. Preparation of NMBBDP Ligand

[0047] The synthetic route is as follows:

[0048]

[0049] 1.1 In a 250ml three-necked flask, add 3g (0.02mol) p-cyanobenzyl chloride 2 and 50mLH 2 O, stir, heat to dissolve. Concentrated HCl (1.28mol, about 80ml) was added dropwise in three batches, refluxed for 5-6h, and cooled to room temperature. Let it stand overnight, adjust the pH value to about 3-4 with NaOH, filter, wash, and wash the solid with H 2 O was washed three times and dried in vacuo to obtain p-hydroxymethylbenzoic acid white solid 3;

[0050] Under cooling in an ice-water bath, in a 100ml three-neck flask, add 15ml of Ac 2 O and 7.6mlHNO 3 , stirred for 30min. Add 2g of p-hydroxymethylbenzoic acid (3) and 15ml of Ac 2 The slurry composed of O, kept stirring during the dropwise addition and kept the temperature not exceeding 0°C. React for 3h, add 30mlH 2 O, ...

Embodiment 2

[0065] The preparation of embodiment 2NMBBDP kit and kit method preparation 99m Tc-labeled osteophilic complex

[0066] 1. The kit is composed of NMBBD ligand, reducing agent stannous chloride, antioxidant vitamin C, excipient glucose and NaCl, and the preparation method is as follows:

[0067] Calculated on the basis of each kit, the mass ratio of various components is as follows: NMBBD ligand, vitamin C, and glucose prepared in Step 1 of Example 1 are 10 mg, 10 mg, and 200 mg in sequence. Weigh each component, mix well, and use After the saline is dissolved, add a certain amount of SnCl 2 2H 2 O hydrochloric acid solution, adjust the pH value to 4-6, filter aseptically, pack in 10mL penicillin bottles, freeze-dry, and seal the cap under vacuum conditions to obtain the NMBBDP kit, and place it in 5- Store in refrigerator at 8°C.

[0068] 2. Prepared by kit method 99m Tc-NMBBDP

[0069] Take 1mL fresh 99m TCO 4 - The eluent (with an activity of about 0.5-1.0mCi) was i...

Embodiment 3

[0070] Embodiment 3 wet preparation 99m Tc-labeled ligand is an osteophilic complex of NHEBDP

[0071] 1. Preparation of NHEBDP Ligand

[0072] The synthetic route is as follows:

[0073]

[0074]1.1 Dissolve 0.01mol of 6-bromohexanoic acid 7 in 10ml of acetonitrile, add dropwise to 3.4g of silver nitrate in 20ml of acetonitrile solution, maintain the temperature at 50°C, after the addition is complete, raise the temperature to 70°C, and react for 6h. This reaction process should avoid light carried. Cool, filter, remove the solvent by rotary evaporation under reduced pressure, add 8ml of water to the residue, extract with ethyl acetate (15mL×3), and dry over anhydrous sodium sulfate. Ethyl acetate was evaporated, and 50ml of ether was added to the residue, and filtered. The filtrate was distilled to remove the solvent, and 6-nitrohexanoic acid 8 was obtained as a light yellow liquid.

[0075] 1.2 Add 10mmol of 6-nitrohexanoic acid 8 prepared in step 1.1 into the three...

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PUM

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Abstract

The invention discloses a novel bone seeking complex. The complex comprises a nuclide <99m>Tc and a ligand. The ligand is a diphosphate derivative containing NO-donors and has a general formula represented by the following formula, wherein R1 is an aliphatic hydrocarbon, an aromatic ring or a nitrogen-containing heterocyclic ring containing 1 to 2 NO-donors; X is a group of -H, -OH, -NH2 and the like; Y is oxygen, sulfur or amino; and n is an integer between 2 and 9. The invention also discloses a preparation method for the complex and application of the complex as a bone imaging agent. Compared with the current bone imaging agent <99m>Tc-MDP widely used in the clinic at home and abroad, the bone imaging agent has high bone tissue initial stage uptake, long stay time and low non-target tissue uptake, particularly low liver uptake, and is expected to become a novel bone imaging agent with better performance.

Description

technical field [0001] The present invention relates to an osteophilic complex, in particular to a 99m Tc-labeled NO-donor bisphosphonic acid complexes and their preparation methods and applications in human or animal organ or tissue imaging agents, especially in bone imaging agents and tumor imaging agents, which belong to Fields of radiopharmaceuticals and nuclear medicine. technical background [0002] Bone is a special connective tissue in which bone is the main component, and it is composed of osteocytes, glial fibers and bone matrix. The content of inorganic salts in the bone matrix is ​​very high, accounting for 65% to 70% of the dry weight of adults, and its main component is hydroxyapatite. [0003] Bisphosphonic acid is a kind of compound with obvious affinity to bone. Studies have shown that the hydroxyl group and two phosphoric acid groups of bisphosphonic acid form a tridentate stable complex with calcium ions in bone, thus making bisphosphonic acid fast and ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K51/04A61K103/10
Inventor 王学斌刘键张现忠唐志刚张俊波陆洁
Owner BEIJING NORMAL UNIVERSITY
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