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Preparation method and application of a fluorescent and radionuclide double-labeled targeting imaging agent

A technology of radionuclide and targeting imaging agent, which is applied in the field of preparation of targeting imaging agent, and can solve the problems of non-specificity of targeting and positioning

Inactive Publication Date: 2011-12-21
张福君 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Although near-infrared fluorophores and radioactive imaging agents have excellent photophysical properties, they are not target-specific

Method used

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  • Preparation method and application of a fluorescent and radionuclide double-labeled targeting imaging agent
  • Preparation method and application of a fluorescent and radionuclide double-labeled targeting imaging agent
  • Preparation method and application of a fluorescent and radionuclide double-labeled targeting imaging agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1 Preparation of double-labeled imaging agent DLIA-IL11Rα (such as figure 1 shown)

[0024] 1. Synthesis of DTPA(OtBu)5-Bz-NH-SA 1.0mmol DTPA(OtBu)5-Bz-NH2 was dissolved in 10ml of DMF / DCM (1 / 5), 1.0mmol succinic anhydride and 0.2mL N, N - Diisopropylethylamine was added to the above solution. The mixture was stirred at room temperature for 4 hours. After the solvent was evaporated in vacuo, the residue was dissolved in ethyl acetate, washed with 2% KHSO4 and brine, then dried over MgSO4. After filtration, the ethyl acetate was removed, leaving DTPA(OtBu)5-Bz-NH-SA as a white powder.

[0025] 2. Two. IR-783-S-Ph-COOH[ figure 1In (2)], 250mg, 0.33mmol of IR-783 and 156mg, 1mmol of 4-mercaptobenzoic acid were dissolved in 5ml of dimethylformamide and stirred overnight at room temperature. The solvent was removed and the residue was dissolved in methanol and precipitated in ether. The solid was filtered and further purified by flash chromatography with ethy...

Embodiment 2

[0033] Embodiment two, DTPA-Bz-SA-Kc (CGRRAGGSC) NH Stability test

[0034] 1. Serum peptide stability test 1 mg DTPA-Bz-NH-SA-Kc (CGRRAGGSC) NH2 was added to 1 ml of 37°C medium containing 10% fetal serum albumin. At various time intervals, 50 μL aliquots were injected into the HPLC system. Samples were eluted with water and acetonitrile containing 0.1% TFA (0-40% varying ratios) for >30 min and detected with a UV / Vis detector (wavelength 230 and 275 nm).

[0035] 2. Mouse whole blood peptide stability test 1mg DTPA-Bz-NH-SA-K-c(CGRRAGGSC)-NH2 was cultured in 200μL mouse whole blood at 37°C, and 20μL of the mixed solution was added to 100 μL of PBS was centrifuged, and 50 μL of the supernatant was injected into the HPLC system. Samples were eluted with water and acetonitrile for >30 min and detected with a UV / Vis detector (wavelength 230 and 275 nm).

[0036] Result: if figure 2 As shown, the peak area of ​​the conjugate can be quantified by HPLC, while the stability is ...

Embodiment 3

[0037] Example 3. Cell binding experiment of double-labeled imaging agent

[0038] 1. In vitro cell binding study of double-labeled imaging agents

[0039] Human breast cancer cells MDA-MB-231 expressing IL-11R α chain and its highly metastatic subline MDA-MB-231(1833) were cultured in MDEM DMEM / F12 medium containing 10% fetal bovine blood Medium, 5% CO2 37 ℃ humidified incubation. Both cell lines were subjected to in vitro cell binding experiments. Add 1 μM double-labeled imaging agent to the cell culture medium, incubate at 37°C for 10 minutes, then add 1 μM Sytox Green to 95% ethanol, and incubate the cells at 4°C Fix and stain for 15 minutes.

[0040] 2. In vivo cell binding study of double-labeled imaging agent

[0041] 1×106 MDA-MB-231 cells were inoculated subcutaneously in the hind limbs of mice. After 3-4 weeks, when the tumor growth diameter reached 7-8 mm, 2 nmol of DLIA-IL11Rα was injected into the tail vein of the mice. Then the mice were subjected to SPECT / C...

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Abstract

The invention discloses a preparation method and application of a fluorescent and radioactive core cord double-labeled targeting imaging agent, belonging to the field of preparation and application of molecular imaging agents in the field of biomedicine. The compound of the present invention is 111In-DTPA-Bz-NH-SA-K(IR-783-S-Ph-CO)-c(CGRRAGGSC)NH2, which is called a double-labeled imaging agent for interleukin 11 receptor alpha chain. The invention consists of three parts: fluorescent imaging agent IR-783-S-Ph-COOH, radionuclide indium-111 and circulating polypeptide. Circulating polypeptide (1) is an ideal carrier of contrast agent, which can be targeted to IL-11Rα chain. The fluorescent imaging agent (2) is connected to the circulating polypeptide through the functional group of lysine. The radionuclide indium-111(3) is first chelated with a metal chelator, and then linked to the circulating polypeptide through the functional group of lysine.

Description

technical field [0001] The invention belongs to the field of preparation and application of molecular imaging agents in biomedicine, and in particular relates to a preparation method and application of a fluorescent and radionuclide double-labeled targeting imaging agent. Background technique [0002] Near-infrared (NIR) fluorescence imaging is a promising field for in vivo noninvasive molecular imaging research. In small animals it is used to detect biomarkers associated with disease expression and provide real-time information on molecular status. In the wavelength range of 700-900 nm, near-infrared light can induce tiny autofluorescence and is rarely absorbed by hemoglobin (mainly absorbing visible light) and water and lipids (mainly absorbing infrared light). In addition, as stable fluorescence can be excited by propagating excitation light, up to 109 photons per second per molecule can be generated from a fluorescence with a fluorescence lifetime of 1 ns. The sensitiv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/08A61K103/20A61K101/02
Inventor 张福君蒋明
Owner 张福君
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