Novel compound and MRI contrast agent containing the same

Abstract

The present invention discloses novel compounds based on picrene and MRI contrast agents containing the same. The novel compounds and MRI contrast agents of the present invention are characterized by a structure in which either an alicyclic compound or an aromatic compound is introduced into the picrene backbone, as shown in Chemical Formula 1-1, resulting in a stable cyclic structure. They also exhibit high magnetic relaxivity and liver targeting.

Description

[Technical Field]

[0001] The present invention relates to a novel compound and an MRI contrast agent containing the same, more specifically to a new type of compound that has a high magnetic relaxivity and can effectively target the liver even in small amounts, and an MRI contrast agent containing the same. [Background technology]

[0002] Magnetic resonance imaging (MRI), a commonly used diagnostic medical device for imaging diagnosis, is gaining attention as a non-invasive diagnostic device, unlike X-rays, because it uses electromagnetic waves to image the water in the human body. MRI contrast agents are used during MRI examinations or surgery to make the internal tissues and blood vessels more visible. The use of MRI contrast agents shortens the time required to obtain images due to the rapid relaxation of water and hydrogen, and tissues are clearly contrasted in the images, improving the accuracy of diagnoses.

[0003] Recently, gadolinium (Gd)-based contrast agents (GBCAs) have become widely used. These agents are compounds in which a gadolinium atom is surrounded by chelating ligands, such as DO3A (1,4,7,10-tetraazacyclododecane 1,4,7-triacetic acid) and PCTA (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid). Depending on the ligand structure, they can be divided into linear GBCAs and ocyclic GBCAs. Due to stability issues, ocyclic GBCAs are preferred for linear GBCAs. Summary of the Invention [Problem to be solved by the invention]

[0004] It is an object of the present invention to provide novel compounds based on the stable cyclic form of pyclen, and MRI contrast agents containing same.

[0005] Another object of the present invention is to provide a compound having high liver targeting ability, and an MRI contrast agent containing the same. [Means for solving the problem]

[0006] Currently, most of the gadolinium contrast agents based on DO3A on the market are used as extracellular formulations, especially those used as liver contrast agents, and most of them have linear structures that reduce stability. Therefore, the present invention provides stable cyclic picrene-based liver-targeting compounds.

[0007] The novel compound according to one aspect of the present invention is represented by the following chemical formula 1. Specifically, the compound has a structure in which a picrene backbone is incorporated with an alicyclic compound or an aromatic compound.

[0008] [Chemical formula 1] [ka]

[0009] In the above formula 1, R may be any one selected from an alicyclic compound or an aromatic compound.

[0010] In one embodiment, in the compound represented by Chemical Formula 1, R may be an alicyclic compound, and the alicyclic compound may be any one selected from cyclohexane or cyclopentane.

[0011] Preferably, the compound of the present invention may be a compound represented by the following chemical formula 1-1.

[0012] [Chemical formula 1-1] [ka]

[0013] The compound represented by Chemical Formula 1-1 may have a structure in which 2-aminocyclohexanol, which has a cyclic structure, is introduced into a gadolinium-bound picrene-based compound. The compound is believed to have a liver-specific targeting effect due to the lipophilic properties of cyclohexane in 2-aminocyclohexanol. 2-aminocyclohexanol has a Log P value of 0.45, demonstrating its lipophilic properties.

[0014] In one embodiment, the compound can specifically target the liver. Unexpectedly, when the compound of the present invention is injected into blood vessels as a contrast agent, it flows into liver cells, exhibiting long-lasting contrast enhancement, and also exhibits a strong contrast enhancement effect in the bile duct. In other words, the compound exhibits specificity for the hepatic and gallbladder systems.

[0015] Another object of the present invention is to provide an MRI contrast agent comprising the compound represented by Chemical Formula 1. The MRI contrast agent of the present invention is a T1 contrast agent, and provides excellent contrast around tumors and lesions, facilitating diagnosis.

[0016] In one embodiment, the MRI contrast agent can be used to diagnose cancer metastasis to the liver, liver cysts, liver cancer, or biliary atresia. [Effects of the Invention]

[0017] According to the present invention, since it has a high magnetic relaxivity, it has the advantage of being able to provide qualitatively improved images, and it can also provide the effect of being able to target the liver even with a small amount as a T1 MRI contrast agent. [Brief explanation of the drawings]

[0018] [Figure 1] 1 is a diagram illustrating a novel compound according to an embodiment of the present invention, a method for producing the same, and an MRI contrast agent including the same. [Figure 2] FIG. 1 is a diagram for comparing and evaluating the kinetic stability of the compound Gd-PCTA-Ach according to one embodiment of the present invention with commercially available contrast agents (Gd-DOTA, Gd-HP-DO3A, Gd-DTPA, Gd-EOB-DTPA, Gd-BOPTA, Gd-DO3A-butrol). [Figure 3a] FIG. 1 is a diagram for comparing and evaluating the pH stability of the compound Gd-PCTA-Ach according to one embodiment of the present invention with that of the commercially available contrast agent Gd-DO3A-butrol, showing the pH stability of 0.5 mM Gd-PCTA-Ach. [Figure 3b] FIG. 1 is a diagram for comparing and evaluating the pH stability of the compound Gd-PCTA-Ach according to one embodiment of the present invention with that of the commercially available contrast agent Gd-DO3A-butrol, showing the pH stability of 1 mM Gd-DO3A-butrol. [Figure 4] 1 shows the results of an experiment to determine whether free Gd3+ exists in the compound Gd-PCTA-Ach according to an embodiment of the present invention. [Figure 5] 1 is a diagram for evaluating the absorbance and fluorescence of 1 mM and 0.5 mM Gd-PCTA-Ach compounds according to an embodiment of the present invention. [Figure 6] 1 shows graphs showing the survival rates of mouse (A) liver cells (AML-12), (B) brain cells (C8-D1A), and (C) kidney cells (Hek-293) at various concentrations of Gd-PCTA-Ach and Gd-DO3A-butrol according to one embodiment of the present invention. [Figure 7]1 shows the Gd content in each organ when Gd-PCTA-Ach according to one embodiment of the present invention is intravenously injected into normal mice. [Figure 8a] MR images of the brain cancer model using injected doses of Gd-PCTA-Ach and Gd-DO3A-butrol are shown. [Figure 8b] 1 shows CNR graphs from MR images of brain cancer models depending on the injected amount of Gd-PCTA-Ach and Gd-DO3A-butrol. [Figure 9a] For comparison of Gd-PCTA-Ach according to one embodiment of the present invention and commercially available contrast agents (Gd-BOPTA, Gd-EOB-DTPA), MR images at 3.0T for each contrast agent flowing into the liver in a normal mouse are shown. [Figure 9b] For comparison of Gd-PCTA-Ach according to one embodiment of the present invention and commercially available contrast agents (Gd-BOPTA, Gd-EOB-DTPA), CNR graphs at 3.0 T for each contrast agent flowing into the liver in a normal mouse are shown. [Figure 10a] Figure 1 shows an image of a normal mouse at 3.0-T using Gd-PCTA-Ach according to one embodiment of the present invention. Yellow arrows indicate the liver and gallbladder. Data are mean ± SD, n=3. [Figure 10b] Figure 1 shows an image of a normal mouse at 9.4-T using Gd-PCTA-Ach according to one embodiment of the present invention. Yellow arrows indicate the liver and gallbladder. Data are mean ± SD, n=3. [Figure 11a] 1 shows the results of 3.0-T MRI on mice with liver cancer using Gd-PCTA-Ach according to one embodiment of the present invention. [Figure 11b] 1 shows a CNR profile for analyzing MRI results for a mouse with liver cancer using Gd-PCTA-Ach according to one embodiment of the present invention. [Figure 11c] 1 shows the results of 3.0-T MRI on mice with liver cancer using Gd-PCTA-Ach according to one embodiment of the present invention. BEST MODE FOR CARRYING OUT THE INVENTION

[0019] Hereinafter, the present invention will be described in detail with reference to the accompanying drawings. The present invention may be modified in various ways and may have various forms, and specific examples are illustrated in the drawings and described in detail herein. However, this is not intended to limit the present invention to the particular disclosed form, but it should be understood that the present invention includes all modifications, equivalents, and alternatives within the spirit and technical scope of the present invention. In describing the various drawings, like reference numerals are used to refer to like elements.

[0020] The terms used in this application are used only to describe specific embodiments and are not intended to limit the present invention. The singular expressions include the plural expressions unless the context clearly dictates otherwise. In this application, the terms "comprise" or "have" are intended to specify the presence of a feature, step, operation, component, part, or combination thereof described in the specification, but should be understood not to preclude the presence or additional possibility of one or more other features, steps, operations, components, parts, or combinations thereof.

[0021] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Terms as defined in commonly used dictionaries should be interpreted to have a meaning consistent with the meaning they have in the context of the relevant art, and should not be interpreted in an idealized or overly formal sense unless expressly defined in this application.

[0022] The novel compounds of the present invention and MRI contrast agents containing the same will be described in more detail below using specific examples and experimental examples. However, the examples of the present invention are merely some embodiments of the present invention, and the scope of the present invention is not limited to the following examples.

[0023] 1 is a diagram illustrating a novel compound according to one embodiment of the present invention, a method for producing the same, and an MRI contrast agent containing the same. Hereinafter, the novel compound of the present invention and examples thereof will be described with reference to FIG. 1.

[0024] Example Compound 1: 2-bromopentanedioic acid L-Glutamic acid (10 g, 67.9 mmol) and NaBr (24.40 g, 237 mmol) were dissolved in 2N HBr solution. NaNO (8.485 g, 123 mmol) was slowly added in small portions as a solid over 1 h at 0 °C. After 2 h 30 min, concentrated sulfuric acid was slowly added dropwise to the yellow mixture at room temperature, and the orange-brown solution was stirred for 20 min. The solution was extracted with diethyl ether (4 × 100 mL), and the combined organic layers were extracted with brine (2 × 100 mL) and dried over NaSO. The solvent was then removed under reduced pressure to give compound 1 without further purification. Yield: 36%.

[0025] Compound 2: Diethyl-2-bromopentanedioate The solution of compound 1 (5.14 g, 24.48 mmol) prepared above was dissolved in EtOH (200 mL, excess). Thionyl chloride (3.55 mL) was slowly added dropwise to the solution at 0 °C. The pale yellow solution was stirred at room temperature for 2 days. The solution was evaporated, and the resulting oil was dissolved in DCM (100 mL). The mixture was extracted with 5% NaHCO (4 × 100 mL), and the combined organic layer was extracted with brine (2 × 100 mL) and dried over NaSO. The solvent was removed under reduced pressure. The resulting product was then purified by column chromatography using petroleum ether and ethyl acetate to obtain compound 2. Yield: 49.2%.

[0026] Compound 3 (3,6,9,15-Tetraazabicyclo[9,3,1]pentadeca-1(15),11,13-triene) Compound 3 was used and supplied by ACG-PHARM.

[0027] Compound 4 (Hexaethyl 2,2',2''-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,6,9-triyl)trigluatrate) A solution of compound 2 (5.98 g, 22.47 mmol) in acetonitrile (ACN) and K2CO3 (4.12 g, 29.88 mmol) was added to a solution of compound 3 (0.77 g, 3.735 mmol) in ACN. The resulting mixture was refluxed at 65 °C for 24 h. The K2CO3 was then removed using a paper filter. After evaporating the filtered solvent, the concentrated solution was added to ethyl acetate (100 mL) and extracted with 0.1 M HCl (4 × 100 mL). The collected aqueous layer was added to 5% NaHCO3 and the pH was adjusted to 7–8 in an ice bath. The solution was then extracted with DCM (3 × 400 mL), and the organic layer was dried over Na2SO4. The solvent was then evaporated to give compound 4 without further purification. Yield: 65%.

[0028] Compound 5(2,2',2''-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,6,9-triyl)triglutaric acid) The compound 4 prepared above was dissolved in EtOH and added to 5M NaOH. The mixture was then refluxed at 80°C for 23 hours. The solvent was evaporated, and the pH of the mixture was adjusted to 7 using HCl (conc. HCl) at 0°C. The resulting product was then purified by ion chromatography without buffering, eluting with water and ACN. After passing through a syringe filter, the solvent was removed and the mixture was lyophilized to obtain the yellow compound 5 without further purification. Yield: 69%

[0029] Compound 6 (GdL) The compound 5 (0.51 g, 0.855 mmol) obtained above was dissolved in HPLC water and the pH was adjusted to 7 with 1 M NaOH. GdCl3 dissolved in water was then slowly added to the solution. The solution was then adjusted to pH 7 with 1 M NaOH and stirred at room temperature for 24 hours. The dark yellow solution was then filtered through paper. The resulting product was purified by prep HPLC using a Hydrosphere C18 column and eluted with neutral water and neutral ACN under the following conditions: 0 min 5% solvent B, 3 min 40% solvent B, 28 min 80% solvent B, 31 min 100% solvent B, 34 min 100% solvent B, 37 min 5% solvent B. After syringe filtering, the product solvent was then evaporated and lyophilized to give compound 6 (GdL) of the present invention.

[0030] Compound 7 (Gd-PCTA-Ach) Compound 6 (1 g, 1.331 mmol) obtained above was dissolved in HPLC water. HOBt (0.359 g, 2.662 mmol) dissolved in dioxane and EDC·HCl (1.27 g, 6.655 mmol) dissolved in water were added dropwise, sequentially, and stirred for 10 minutes. 2-Aminocyclohexanol (0.91 g, 7.986 mmol) dissolved in water was added slowly, and the pH was adjusted to 6 with 1 M HCl. The mixture was then stirred at room temperature for 24 hours. The mixture was then filtered through paper. The resulting product was purified by prep HPLC in two steps using a Triart C18 column. First, the elution conditions (flow rate: 12 mL / min) were water and MeOH: 0 min 0% solvent B, 5 min 0% solvent B, 60 min 90% solvent B, 70 min 90% solvent B, and 75 min 0% solvent B. Second, the elution conditions (flow rate: 12 mL / min) were ACN: 0 min 0% solvent B, 5 min 0% solvent B, 60 min 90% solvent B, 70 min 90% solvent B, and 75 min 0% solvent B. Then, after syringe filtering, the product solvent was evaporated and freeze-dried to obtain the compound of the present invention Gd-PCTA-Ach. Yield: 10%.

[0031] Comparative Example To evaluate the performance of the Gd-PCTA-Ach of the present invention, commercially available contrast agents, Dotarem (Gd-DOTA), Prohance (Gd-HP-DO3A), Magnevist (Gd-DTPA), Primovist (Gd-EOB-DTPA), Multihance (Gd-BOPTA), Gadovist (Gd-DO3A-butrol), and Gadopiclenol, were used as comparative examples. Dotarem, Prohance, Magnevist, Primovist, Multihance, and Gadovist are registered trademarks.

[0032] 2 to 11 are diagrams showing the results of each of the experimental examples of the present invention. Hereinafter, the properties of the novel compound of the present invention and its effect as an MRI contrast agent will be described with reference to FIGS.

[0033] Experimental example Experimental Example 1: Relaxivity and HSA binding evaluation The relaxivities (r1 and r2), water-soluble (Log P), and HSA binding affinity of the compound Gd-PCTA-Ach of the present invention and a commercially available contrast agent were compared and evaluated. Relaxivities (r1 and r2) were measured in water and HSA under magnetic fields of 3.0 T and 9.4 T, respectively. HSA binding affinity was measured using ultrafiltration analysis. The measurement results are summarized in Table 1 below.

[0034] [Table 1]

[0035] Referring to Table 1, the Gd-PCTA-Ach of the present invention was found to have higher relaxivity (r1 and r2) than the commercially available contrast agent under all conditions.

[0036] The Log P value is a value used to evaluate hydrophilicity; when the P value is less than 1, the Log P value becomes a negative number, indicating hydrophilicity, and when the P value is greater than 1, the Log P value becomes a positive number, indicating lipophilicity. Gd-PCTA-Ach of the present invention was confirmed to have hydrophilicity because its Log P value was a negative number of -1.0.

[0037] Meanwhile, the binding percentage of Gd-PCTA-Ach was three times higher than that of Gd-BOPTA and Gd-EOB-DTPA. Based on the new hydrolysis results, the log P value indicates a strong interaction with blood proteins such as HSA, and the HSA binding analysis data supports this. Consequently, based on the high HSA binding value of 30, it can be concluded that Gd-PCTA-Ach remains in the blood for a long time. While the HSA binding analysis suggests that Gd-PCTA-Ach has a long blood retention half-life, actual hepatocyte accumulation in vivo remains to be investigated, regardless of whether there is a greater interaction with HSA or whether it transports hepatocyte proteins. Further evidence for hepatocyte accumulation was provided by in vivo MRI experiments.

[0038] Experimental Example 2: Stability evaluation (1) Dynamic stability evaluation The kinetic stability is due to the ligand-bound Gd 3+ This experiment was conducted to examine how much free Gd is exchanged with zinc, which is abundantly distributed in the human body. 3+ (Free Gd 3+) (transmetalation) is toxic and harmful to the human body. Therefore, it is important not to exchange for long periods of time. In a kinetic stability experiment, commercially available contrast agents (Gd-DOTA, Gd-HP-DO3A, Gd-DTPA, Gd-EOB-DTPA, Gd-BOPTA, Gd-DO3A-butrol) were compared with two concentrations of Gd-PCTA-Ach (1.5 mM, 1 mM), and the results are shown in Figure 2.

[0039] Referring to Figure 2, the intracellular Gd concentration changes over time. 3+ The results of 72-hour follow-up observations showed that Gd-PCTA-Ach showed a similar tendency to Gd-DOTA, Gd-HP-DO3A, and Gd-DO3A-butrol, but was higher than Gd-DTPA, Gd-EOB-DTPA, and Gd-BOPTA.

[0040] (2) pH stability evaluation The pH stability test is an experiment to confirm the stability of a drug at various pH levels. The human body normally maintains a pH of approximately 7.4, but since the pH varies slightly from part to part, it is also important to confirm the stability at various pH levels. The pH stability test was conducted for 72 hours, the same as the kinetic stability evaluation, and stability was confirmed at pH levels of 1, 4, 7, and 10. The results are shown in Figure 3.

[0041] 3, it can be seen that the pH was maintained constant for 72 hours. Although the value varied depending on the pH, stability was observed. Gd-PCTA-Ach of the present invention showed higher stability as the pH increased, and at pH 7 or higher, it showed lower stability than the commercially available contrast agent Gd-DOTA.

[0042] Experimental Example 3: Evaluation of other chemical properties (1) Freedom Gd 3+ (free Gd 3+ ) existence evaluation Freedom Gd 3+ Since Gd is toxic, free Gd was not added to the synthesized Gd-PCTA-Ach. 3+ Experiments were carried out to determine whether free Gd3+ The presence of was confirmed by graphing with the dye Arsenazo III, and the results are shown in Figure 4.

[0043] Referring to FIG. 4, the Gd-PCTA-Ach of the present invention reacts with Arsenazo III and free Gd 3+ Unlike the purple and red forms, it is free Gd 3+ We confirmed that there was no

[0044] (2) Absorbance and fluorescence evaluation Experiments were carried out to determine the absorption and emission wavelengths of the Gd-PCTA-Ach synthesized according to the present invention. The Gd-PCTA-Ach concentrations were 1 mM and 0.5 mM, respectively, and the results are shown in Figure 5. Referring to FIG. 5, the absorption wavelength was highest at 270 nm, and the emission wavelength was highest at 315 nm.

[0045] Experimental Example 4 Cytotoxicity Figure 6 shows the cytotoxicity experiments of Gd-PCTA-Ach and Gd-DO3A-butrol in mouse (A) liver cells (AML-12), (B) brain cells (C8-D1A), and (C) kidney cells (Hek-293). Gd-DO3A-butrol was used as the positive group, and the cells were incubated with the drugs for 24 hours.

[0046] Referring to FIG. 6, when comparing Gd-PCTA-Ach of the present invention with Gd-DO3A-butrol, it was confirmed that Gd-PCTA-Ach of the present invention, along with commonly used Gd-DO3A-butrol, had no cytotoxicity.

[0047] Experimental Example 5: Biodistribution evaluation To confirm the biodistribution, the compound of the present invention (Gd-PCTA-Ach) was intravenously injected into normal mice, and ICP was used to confirm which organs detected the compound 15 minutes, 30 minutes, 2 hours, and 24 hours later.

[0048] Figure 7 shows the Gd content in each organ. High intensity was measured in the liver and kidney, confirming that Gd-PCTA-Ach flows into the liver. It was also detected in the gallbladder (GB) and blood vessels. These results demonstrate that the present invention has similar properties to Gd-BOPTA, a commercially available contrast agent used as a hepatobiliary-specific contrast agent.

[0049] Experimental Example 6: Video Evaluation After creating a brain cancer model using C6 glioma cells, 0.1 mmol / kg Gd-PCTA-Ach, 0.05 mmol / kg Gd-PCTA-Ach, and 10.1 mmol / kg Gd-DO3A-butro were injected, and (a) MR images and (b) CNR graphs from the MR images were obtained. The results are shown in Figure 8.

[0050] Referring to Figure 8, (a) it was observed that brain cancer lesions appeared brighter at 0.1 mmol / kg of the present invention's Gd-PCTA-Ach than at 0.1 mmol / kg of Gd-DO3A-butrol. Furthermore, 0.1 mmol / kg of Gd-DO3A-butrol exhibited similar brightness to 0.05 mmol / kg, half the concentration of Gd-PCTA-Ach. (b) It can be seen that the CNR changes for 0.1 mmol / kg Gd-DO3A-butrol and 0.05 mmol / kg Gd-PCTA-Ach were similar. Therefore, it can be seen that the present invention's Gd-PCTA-Ach can provide images of similar brightness even when used at a lower concentration than the commercially available contrast agent Gd-DO3A-butrol.

[0051] Figure 9 shows (a) MR images and (b) CNR graphs at 3.0 T for comparison of Gd-PCTA-Ach according to one embodiment of the present invention and commercially available contrast agents (Gd-BOPTA, Gd-EOB-DTPA) flowing into the liver in a normal mouse.

[0052] Referring to Figure 9, liver parenchyma was observed 5 minutes after injection of all three MR contrast agents, followed by a gradual decrease. Meanwhile, the bile (gallbladder) was observed somewhat differently. For Gd-BOPTA and Gd-EOB-DTPA, CA showed an initial increase followed by a gradual decrease, while for Gd-PCTA-Ach, a gradual increase was observed from 5 to 120 minutes. Clearance of all three MR CAs was confirmed 24 hours after intravascular injection. Gd-PCTA-Ach uniquely exhibited a transient blood enhancement compared to the other agents. These results indicate that Gd-PCTA-Ach entered the liver with slightly lower enhancement than Gd-BOPTA and Gd-EOB-DTPA.

[0053] Figure 10 shows images of a normal mouse at (a) 3.0-T and (b) 9.4-T using Gd-PCTA-Ach according to one embodiment of the present invention. Gd-PCTA-Ach was intravenously injected into the mouse at a dose of 0.1 mmol / kg.

[0054] Referring to Figure 10, it is generally known that relaxivity decreases as MHz increases. Looking at the MR image patterns of the Gd-PCTA-Ach of the present invention as the magnetic field changes (3.0T (64MHz) -> 9.4T (400MHz)), it was confirmed that the relaxivities r1 and r2 of Gd-PCTA-Ach decreased as the magnetic field change increased. Therefore, the contrast improved, showing brighter image quality at 3T than at 9.4T.

[0055] Figure 11 shows (a, c) 3.0-T MRI results for mice with liver cancer using Gd-PCTA-Ach according to one embodiment of the present invention, and (b) a CNR distribution diagram for analyzing the MRI results. Experimental mice were induced by injecting HepG2 cell lines into mice with orthotopic hepatocellular carcinoma (HCC) and allowing them to grow until tumors reached a sufficient size. After tumor formation, the HCC experimental mice were intravenously injected with 0.1 mmol / kg of Gd-PCTA-Ach.

[0056] Referring to Figure 11, T2-weighted images were used to confirm tumor location before Gd-PCTA-Ach injection. The tumor was not clearly visible in the pre-injection T1-weighted image (a). Five minutes after Gd-PCTA-Ach injection, not only was the boundary between the normal and tumor groups clearly visible, but the tumor itself was slightly enhanced and then gradually decreased (A and c). HCC is known to be an angiogenic tumor. It is assumed that Gd-PCTA-Ach enters the tumor blood vessels, resulting in tumor liver enhancement. As shown in (b), the Gd-PCTA-Ach enhancement effect showed a significant improvement at 5 minutes, followed by a gradual decrease.

[0057] Although the present invention has been described above with reference to preferred embodiments, it should be understood that those skilled in the art can make various modifications and changes to the present invention without departing from the spirit and scope of the present invention as set forth in the following claims.

Claims

1. A compound represented by the following chemical formula 1: [Chemical formula 1] 【Chemical 1】 In Formula 1, R represents any one selected from an alicyclic compound or an aromatic compound.

2. In Formula 1, R is an alicyclic compound; The compound according to claim 1, wherein the alicyclic compound is any one selected from the group consisting of cyclohexane and cyclopentane.

3. The compound according to claim 2, which is represented by the following chemical formula 1-1: [Chemical formula 1-1] 【Chemistry 1-1】

4. The compound of claim 1, wherein the compound specifically targets the liver.

5. MRI contrast agent containing a compound according to any one of claims 1 to 4.

6. 6. The MRI contrast agent according to claim 5, which is used for diagnosing cancer metastasis to the liver, liver cysts, liver cancer, or biliary atresia.

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