KR101351411B1 - Method for diagnosing selectively malignant tumor by differentiating malignant tumor and inflammation in F-18 FDG positron emission tomography using pioglitazone - Google Patents

Abstract

The present invention relates to a method for selectively diagnosing malignant tumors by distinguishing malignant tumors from inflammatory lesions in F-18 FDG positron emission tomography using pioglitazone, and specifically, to treat pioglitazone in F-18 FDG positron emission tomography. Malignant tumors when diagnosed with positron emission tomography by increasing the intake of F-18 FDG only in malignant tumor lesions and slightly increasing or decreasing the intake of F-18 FDG in inflammatory lesions compared to untreated pioglitazone. It is characterized by selectively diagnosing malignant tumor lesions and inflammation.

Description

Method for diagnosing selectively malignant tumor by differentiating malignant tumor and inflammation in F-18 FDG positron emission tomography using F-18 FDV positron emission tomography using pioglitazone pioglitazone}

The present invention relates to a method for selectively diagnosing malignant tumors by distinguishing malignant tumors from inflammatory lesions by treatment with pioglitazone in F-18 FdV positron emission tomography.

In terms of medical technology, screening for malignant tumor patients or accurately finding malignant tumor lesions of malignant tumor patients during surgery is very important in accurately diagnosing a patient's condition or determining a surgical range. In addition, identifying lesions other than malignant tumors has a very important effect on the patient's prognosis.

In the recent diagnosis of the disease, fluorescence, bioluminescence, single photon emission computed tomography (SPECT), computed tomography (CT), magnetic resonance tomography (SCT) are used to find lesions in the body without surgery. A variety of molecular imaging techniques are used, including magnetic resonance imaging (MRI), positron emission tomography (PET), ultrasound, etc. Molecular imaging is a non-invasive in vivo study of molecular biology and cell biology. It is a technique of imaging the changes of molecular level occurring in living plants by applying to imaging, and it is a new field that combines the development of molecular cell biology and advanced imaging technology.

This molecular imaging technique is used for early diagnosis of cancer, drug development, chemotherapy, and monitoring of gene-stem cell therapy. In addition, molecular imaging is an important part of translational research that can be imaged repeatedly without damaging biological tissues, making it possible to use cellular-level basic research in clinical practice.

Among the molecular imaging techniques, positron emission tomography (PET) is a nuclear medicine test method that can display physiological, chemical and functional images of the human body in three dimensions using radiopharmaceuticals emitting positrons. It is mainly used in the diagnosis of cancer, and is known as a useful test for differential diagnosis of cancer, staging, recurrence evaluation, and treatment effect determination. In addition, positron emission tomography can be used to obtain receptor images or metabolic images for evaluation of heart disease, brain disease and brain function.

Radioactive isotopes for positron emission tomography are fluorine (F-18), carbon (C-11), oxygen (O-15), nitrogen (N-13), etc. Metabolism, drug metabolism and receptor imaging are possible. These radioisotopes can also be used to make radiopharmaceuticals that are tracers that reflect specific physiological, chemical and functional changes. The most commonly used radiopharmaceutical is F-18 FDG (fluoro-2-deoxy-D-glucose), which is a glucose-like substance that, when injected, collects a lot of glucose metabolism in the body, such as cancer. . Malignant tumor cells require more energy than normal cells or benign tumor cells, which consume a significant amount of glucose as an energy source. The mechanism by which malignant tumor cells increase glucose uptake increases the expression of glucose transporters in the cell membranes of malignant tumor cells and increases the expression of hexokinase, which is required for the use of glucose as energy in the cytoplasm. Ingestion effects are seen in malignant tumors. In addition, FDG is a glucose analogue that is ingested into cells through the glucose transporter of the cell membrane and phosphorylated as a substrate for hexokinase. However, since the next step, glycolysis, does not proceed and accumulates in the cell in a phosphorylated state, a clear image can be obtained. In addition, unlike glucose, it is not reabsorbed in the proximal convoluted tubule of the kidney and discharged out of the body through the urinary system.

Therefore, positron emission tomography, especially positron emission tomography using F-18 FDG, can be used to diagnose, stage, and treat malignant tumor patients not only in Korea but also worldwide. It is used in a wide range of areas, including policy, prognosis, and recurrence, and is known for its high accuracy in disease diagnosis.

However, although the intake of F-18 FDG is made in malignant tumor cells, the two lesions are similarly observed in positron emission tomography images because they are also ingested in macrophages or inflammatory cells in inflammatory lesions. In other words, the increase in FDG uptake occurs not only in malignant tumors but also in inflammatory lesions that are not normal, so whether the intake of F-18 FDG in these lesions is due to malignant tumor translocation or simple inflammation of glucose intake. It is difficult to diagnose correctly through. Therefore, it is often difficult to diagnose malignant tumor patients or inflammatory patients. However, since the treatment of malignant tumors and inflammation is completely different, it is very important to clinically distinguish between malignant tumors and inflammation. Therefore, it is necessary to develop a method for selectively and accurately diagnosing malignant tumors in positron emission tomography using F-18 FDG.

On the other hand, PPAR-γ (peroxisome proliferator-activated receptor-γ) is a ligand-dependent transition factor, mainly expressed in adipose tissue, present in small amounts in the colon, kidney, muscle, liver, and is associated with adipose tissue production. In addition, PPAR-γ is known to play an important regulatory role in glucose metabolism and cell growth, and is an important immunomodulator found in immune tissue cells such as monocytes / macrophages. Has been reported to have anti-inflammatory effects. It is also reported that PPAR- [gamma] can inhibit the progression of diabetic nephropathy.

As described above, although the anti-inflammatory and anti-diabetic effects of PPAR-γ agonists are known, there are few examples of PPAR-γ agonists used for positron emission tomography using F-18 FDG. It is insignificant.

Therefore, F-18 FDG positron emission tomography using the anti-inflammatory effects of PPAR-γ agonists can be used to detect F-18 FDG intake only in malignant tumor lesions by PPAR-γ agonists when diagnosing malignant tumors and inflammation. Increasingly, it is thought that selective diagnosis of malignant tumors is possible.

The inventors of the present invention have been studying how to distinguish malignant tumors from inflammatory lesions and selectively diagnose malignant tumor lesions in the F-18 FDG positron emission tomography, while treating pioglitazone in F-18 FDG positron emission tomography. In one case, the intake of F-18 FDG was increased only in malignant tumor lesions compared with the absence of pioglitazone, and in inflammatory lesions, the intake of F-18 FDG was slightly increased or decreased. It was confirmed that only malignant tumor lesions can be selectively diagnosed by distinguishing inflammatory lesions, thereby completing the present invention.

Accordingly, the present invention is to provide a method for selectively diagnosing malignant tumors by distinguishing malignant tumors from inflammatory lesions in F-18 FdX positron emission tomography using pioglitazone.

The present invention provides a method for selectively diagnosing malignant tumors by distinguishing malignant tumors from inflammatory lesions in F-18 FdX positron emission tomography using pioglitazone.

Hereinafter, the present invention will be described in detail.

The method for selectively diagnosing malignant tumors in F-18 FDG positron emission tomography using pioglitazone according to the present invention is characterized in that malignant tumors are treated when pioglitazone is treated in F-18 FDG positron emission tomography. It is characterized by increasing the intake of F-18 FDG only in lesions, and slightly increasing or decreasing the intake of F-18 FDG in inflammatory lesions.

The pioglitazone according to the present invention shows high expression of GLUT1 protein and GLUT1 / Actin in malignant tumor cells, and low expression of GLUT1 protein and low GLUT1 / Actin in macrophages (RAW 264.7), thereby reducing glucose in malignant tumor cells. It can be seen that the concentration is low. Therefore, when F-18 FDG is treated to malignant tumor cells treated with pioglitazone, the intake of F-18 FDG may be expected to increase.

In addition, pioglitazone according to the present invention significantly increases the intake of F-18 FDG in malignant tumor lesions, but slightly increases the intake of F-18 FDG in normal cells, and clear images in malignant tumor lesions on positron emission tomography images. Ever change.

In addition, pioglitazone according to the present invention significantly increases the intake of F-18 FDG in malignant tumor lesions of mice in which both malignant and inflammatory lesions are present, and slightly increases the intake of F-18 FDG in inflammatory lesions. Decrease. In addition, the pioglitazone of the present invention shows an image change only in malignant tumor lesions on positron emission tomography images, and almost no image change in inflammatory lesions. Therefore, it can be seen that there is a difference in the intake of F-18 FDG by pioglitazone in malignant tumor lesions and inflammatory lesions.

As described above, pioglitazone according to the present invention significantly increases the intake of F-18 FDG in malignant tumor lesions and slightly increases or decreases the intake of F-18 FDG in inflammatory lesions, thereby positron emission tomography imaging. When malignant tumor and inflammation are distinguished, only malignant tumor lesion can be diagnosed selectively.

Therefore, the method for selectively diagnosing malignant tumors in F-18 FDG positron emission tomography using pioglitazone according to the present invention includes identifying cancer lesions in tuberculosis patients, distinguishing lymph node involvement and lymphadenitis in lymphoma patients, and lymph nodes in cancer patients. It can be applied to confirm the presence of metastasis, to distinguish between recurrence and residual cancer lesion after cancer surgery and inflammatory lesion after surgery, or to distinguish between residual or recurrent cancer after radiation therapy and inflammatory lesion after radiation therapy in cancer patients. .

In the present invention, malignant tumors are oral cancer, cerebrospinal cancer, head and neck cancer, lung cancer, breast cancer, thymic tumor, mesothelioma, esophageal cancer, gastric cancer, colon cancer, liver cancer, pancreatic cancer, biliary tract cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, germ cell tumor, ovary Cancer, cervical cancer, endometrial cancer, lymphoma, acute leukemia, chronic leukemia, multiple myeloma, sarcoma, malignant melanoma, skin cancer.

Pioglitazone according to the present invention significantly increases the intake of F-18 FDG in malignant tumor lesions, and slightly increases or decreases the intake of F-18 FDG in inflammatory lesions, thereby preventing malignant tumors and inflammation in positron emission tomography imaging. Only malignant tumor lesions can be selectively diagnosed.

1 is a diagram showing the expression level of glucose transport protein (GLUT1) and GLUT1 / Actin value according to pioglitazone concentration in malignant tumor cells [oral cancer cell (KB), breast cancer cell (MDA-MB-231), lung cancer cell (A549). ), Macrophages (RAW 264.7)].
2 is a diagram showing a positron emission tomography image obtained by injecting pioglitazone and injecting F-18 FDG in 1 hour after F-18 FDG injection into a mouse inducing malignant tumor (lung cancer) (arrow is malignant) Tumor lesions).
FIG. 3 is a diagram showing positron emission tomography images obtained by injecting pioglitazone and injecting F-18 FDG into the mice induced with malignant tumors (lung cancer) after 24 hours of infusion (arrow is malignant). Tumor lesions).
4 is a diagram showing positron emission tomography images obtained by injecting F-18 FDG into malignant tumors (lung cancer) and inflammation-induced mice after 2 hours of injecting pioglitazone and injecting F-18 FDG (dotted line). Circles represent malignant tumor lesions and inflammatory lesions).
5 is a diagram showing positron emission tomography images obtained by injecting F-18 FDG into malignant tumors (lung cancer) and inflammation-induced mice after injecting pioglitazone and injecting F-18 FDG after 24 hours (dotted line). Circles represent malignant tumor lesions and inflammatory lesions).
6 is a diagram showing positron emission tomography images obtained by injecting F-18 FDG into malignant tumors (breast cancer) and inflammation-induced mice after 2 hours of injecting pioglitazone and injecting F-18 FDG (dotted line). Circles represent malignant tumor lesions and inflammatory lesions).
7 is a diagram showing a positron emission tomography image obtained by injecting F-18 FDG into a malignant tumor (breast cancer) and inflammation-induced mice after 24 hours of injecting pioglitazone and injecting F-18 FDG (dotted line). Circles represent malignant tumor lesions and inflammatory lesions).

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.

Example  One  In malignant tumor cells Fioglitazone  Effect on Glucose Intake

To determine the effect of pioglitazone on glucose uptake in malignant tumor cells, the following experiment was performed.

Specifically, oral cancer cells (KB), breast cancer cells (MDA-MB-231), lung cancer cells (A549), and macrophages (RAW 264.7) are each seeded at a cell size of 1 × 10 ^{6 in} a ⁶ cm culture dish, Each cell was incubated for 12 hours in RPMI-1640 culture medium containing 10% FBS (fetal bovine serum) and 1% antibiotic in a CO ₂ incubator. Each cell was then treated with pioglitazone by concentration (10, 50, 100, 150 μM) and incubated in a CO ₂ incubator for 1 hour. The culture medium treated with pioglitazone was removed and each cell was washed twice with phosphate buffer (pH 7.4), then 20 mM Tris-HCl (pH 7.4), 2 mM EDTA, 1 mM Na ₃ VO ₄ (sodium orthovanadate), 0.1 mM Intracellular proteins were extracted by collecting the cells attached to the culture dish using a lysis buffer containing PMSF (phenylmethylsulfonyl fluoride) and protease inhibitors. The extracted protein was quantified, 35 μg of which was loaded onto an acrylamide gel (electrophoresis gel used in western blot) and subjected to SDS-PAGE. After electrophoresis, the protein in the gel was transferred to the PVDF membrane through the transfer process, and reacted for 1 hour in a 5% skim milk powder solution (blocking solution) so that only the protein band on the PVDF membrane was exposed to the surface. Then, the cells were washed with phosphate buffer (pH 7.4), diluted with a primary IgG antibody against GLUT1 produced in rabbit 1: 500, treated with PVDF membrane, and reacted at 4 ° C. for at least 12 hours. The PVDF membrane was washed with phosphate buffer (pH 7.4) to remove the primary antibody remaining on the membrane, and the anti-rabbit IgG secondary antibody generated in goats with horseradish peroxidase (HRP) bound was diluted 1: 2500 to PVDF membrane. And reacted at room temperature for 1 hour. The PVDF membrane was washed with phosphate buffer (pH 7.4) to remove the secondary antibody remaining on the membrane, and the ECL (enhanced chemiluminescence) solution detection kit and luminescent image analyzer (LAS-3000, Fuji Film, Japan) were used. The expression level of GLUT1 protein bound to the antibody was confirmed. GLUT1 protein is known to be expressed low when the glucose concentration is high, and high when the glucose concentration is low.

The results are shown in Figure 1 and Table 1.

GLUT1 / Actin Value by Pioglitazone Treatment in Oral Cancer Cells (KB), Breast Cancer Cells (MDA-MB-231), Lung Cancer Cells (A549), Macrophages (RAW 264.7) Pioglitazone (μM) 0 10 50 100 150 Oral Cancer Cells (KB) One 1.80 3.29 5.12 3.83 Breast Cancer Cells (MDA-MB-231) One 0.94 1.04 0.92 2.03 Lung Cancer Cells (A549) One 1.04 1.71 1.81 3.02 Macrophage (RAW 264.7) One 0.86 1.19 0.81 0.63

As shown in FIG. 1 and Table 1, the expression of GLUT1 protein and GLUT1 / Actin were high by pioglitazone treatment in oral cancer cells (KB), breast cancer cells (MDA-MB-231), and lung cancer cells (A549). In contrast, macrophages (RAW 264.7) showed low GLUT1 protein expression and GLUT1 / Actin values. Therefore, it can be seen that the glucose concentration is low in malignant tumor cells, and the results of this study can be expected to increase the intake of F-18 FDG when F-18 FDG treatment to malignant tumor cells treated with pioglitazone.

Example  2  : In malignant tumor (lung cancer) lesion In pioglitazone  By F-18 FDG Changes in intake

In order to observe the change in intake of F-18 FDG by pioglitazone in malignant tumor (lung cancer) lesions, the following experiment was performed.

Specifically, lung cancer cells (A549) are injected into the right hind limb of 4-5 week-old mice (Japan SLC, Inc.) to form malignant tumors (lung cancer), and cultured to about 1 cm to prepare a xenografted mouse. Fasting 12 hours before positron emission tomography (PET) imaging. Mice were injected intravenously with 0.1 ml of F-18 FDG (3.7 × 10 ⁵ Bq, 100 μCi) and positron emission tomography was performed 30 minutes later to obtain an image. After 1 hour, 400 μg of pioglitazone was dissolved in 100 μl of DMSO solution diluted with saline solution, and then injected intraperitoneally into the mouse, and 30 minutes later, 0.1 mL of F-18 FDG (3.7 × 10 ⁵ Bq, 100 μCi) was injected intravenously. After injection, positron emission tomography was performed to obtain an image. The experimental conditions were actually prepared by considering the clinical positron emission tomography conditions, and the experimental conditions were determined by considering the conditions when pioglitazone was applied to humans. In addition, the infusion amount of pioglitazone was also determined in consideration of the mouse weight based on the single dose prescribed for diabetic patients.

The results are shown in Figure 2 and Table 2.

Intake of F-18 FDG in malignant tumor (lung cancer) lesions obtained by injection of pioglitazone and F-18 FDG in 1 hour after F-18 FDG was injected into mice with malignant tumors (lung cancer) Intake of F-18 FDG (% ID / g) Intake of F-18 FDG
Increase Before pioglitazone injection After pioglitazone injection Malignant tumor (lung cancer) lesion 2.49 3.00 20.5%

※% ID / g: The percentage of F-18 FDG radiation present per unit weight of the tissue or organ to be measured, based on the actual dose of F-18 FDG.

As shown in Figure 2 and Table 2, the intake of F-18 FDG in malignant tumor (lung cancer) lesions increased about 20.5% after injection compared to before pioglitazone injection, malignant tumor after injection compared to before pioglitazone injection in positron emission tomography A clear visual increase was observed in (lung cancer) lesions. Therefore, it can be seen that the intake of F-18 FDG is selectively increased by pioglitazone in malignant tumor lesions.

Example  3  : In malignant tumor (lung cancer) lesion In pioglitazone  By F-18 FDG Changes in intake

After excluding the effects of F-18 FDG taken before pioglitazone injection in malignant tumor (lung cancer) lesions, the following experiment was performed to observe the change in the intake of F-18 FDG by pioglitazone.

Specifically, lung cancer cells (A549) are injected into the right hind limb of 4-5 week-old mice (Japan SLC, Inc.) to form malignant tumors (lung cancer), and cultured to about 1 cm to prepare a xenografted mouse. Fasting 12 hours before positron emission tomography imaging. Mice were injected intravenously with 0.1 ml of F-18 FDG (3.7 × 10 ⁵ Bq, 100 μCi) and positron emission tomography was performed 30 minutes later to obtain an image. Subsequently, after 24 hours of no effect on positron emission tomography images, radioactivity from F-18 FDG disappeared, 400 μg of pioglitazone was dissolved in 100 μl of DMSO solution diluted with saline, and then mouse 30 minutes after intraperitoneal injection, 0.1 ml of F-18 FDG (3.7 × 10 ⁵ Bq, 100 μCi) was intravenously injected, followed by positron emission tomography. Radioactive isotopes can be judged to have completely deactivated after five to six half-lives, so that after 24 hours, the activity of F-18 FDG with a half-life of two hours has disappeared from the body of the mouse.

The results are shown in Figure 3 and Table 3.

Intake of F-18 FDG in malignant tumors (lung cancer) lesions and normal cells obtained by injecting pioglitazone and F-18 FDG in 24 hours after F-18 FDG was injected into mice with malignant tumors (lung cancer) Intake of F-18 FDG (% ID / g) Intake of F-18 FDG
Increase Before pioglitazone injection After pioglitazone injection Malignant tumor (lung cancer) lesion 3.88 7.11 83.2% Normal cell 1.28 1.36 6.3%

※% ID / g: The percentage of F-18 FDG radiation present per unit weight of the tissue or organ to be measured, based on the actual dose of F-18 FDG.

As shown in FIG. 3 and Table 3, the intake of F-18 FDG in malignant tumor (lung cancer) lesions was increased by about 83.2% after injection compared to before pioglitazone injection, and intake of F-18 FDG before and after pioglitazone injection in normal cells. Slightly increased to 6.3%. In addition, positron emission tomography images showed a clear visual increase in malignant tumors (lung cancer) after injection compared to before pioglitazone injection. Therefore, it can be seen that the intake of F-18 FDG is selectively increased by pioglitazone in malignant tumor lesions.

Example  4  : In malignant tumors (lung cancer) and inflammatory lesions In pioglitazone  Changes in intake of F-18 FDG

In order to observe the change in intake of F-18 FDG by pioglitazone in mice having both malignant tumor (lung cancer) lesion and inflammatory lesion, the following experiment was performed.

Specifically, lung cancer cells (A549) are injected into the right hind limb of 4-5 week-old mice (Japan SLC, Inc.) to form malignant tumors (lung cancer), cultured to about 0.8 cm, and then into the left hind limb of the mouse. 100 μl of turpentine oil was injected to induce inflammation to prepare a xenograft mouse in which both malignant tumor (lung cancer) and inflammation exist. The xenografted mice were fasted 12 hours before positron emission tomography imaging. Mice were injected intravenously with 0.1 ml of F-18 FDG (3.7 × 10 ⁵ Bq, 100 μCi) and positron emission tomography was performed 30 minutes later to obtain an image. Subsequently, 400 μg of pioglitazone was dissolved in 100 μl of DMSO solution diluted with saline after 2 hours of one half-life, followed by intraperitoneal injection into mice and 30 minutes after F-18 FDG (3.7 × 10 ⁵ Bq, 100 μCi) 0.1 After intravenous injection of ㎖, positron emission tomography was performed to obtain an image.

The results are shown in Figure 4 and Table 4.

2 hours after F-18 FDG injection into malignant tumor (lung cancer) and inflammation-induced mice, F-18 FDG in malignant tumor (lung cancer) lesion and inflammatory lesion obtained by pioglitazone injection and F-18 FDG injection Intake of Intake of F-18 FDG (% ID / g) Intake of F-18 FDG
Increase Before pioglitazone injection After pioglitazone injection Malignant tumor (lung cancer) lesion 3.47 3.20 -7.78% Inflammatory lesions 3.93 3.34 -15.0%

※% ID / g: The percentage of F-18 FDG radiation present per unit weight of the tissue or organ to be measured, based on the actual dose of F-18 FDG.

As shown in Figure 4 and Table 4, the intake of F-18 FDG in malignant tumor (lung cancer) lesions and inflammatory lesions was reduced both before and after pioglitazone injection, especially intake of F-18 FDG in inflammatory lesions Lung cancer), which is about 2 times less than that of the lesion. In addition, positron emission tomography images showed a visual increase in malignant tumors (lung cancer) lesions after injection compared to before pioglitazone injection, but there was almost no difference in inflammatory lesions. Therefore, it can be seen that there is a difference in the intake of F-18 FDG by pioglitazone in malignant tumor lesions and inflammatory lesions.

Example  5  : In malignant tumors (lung cancer) and inflammatory lesions In pioglitazone  Changes in intake of F-18 FDG

In order to observe the change in the intake of F-18 FDG by pioglitazone after excluding the effect of F-18 FDG taken before pioglitazone injection in mice with both malignant (lung cancer) lesions and inflammatory lesions, The experiment was performed.

Specifically, lung cancer cells (A549) are injected into the right hind limb of 4-5 week-old mice (Japan SLC, Inc.) to form malignant tumors (lung cancer), cultured to about 0.8 cm, and then into the left hind limb of the mouse. 100 μl of turpentine oil was injected to induce inflammation to prepare a xenograft mouse in which both malignant tumor (lung cancer) and inflammation exist. The xenografted mice were fasted 12 hours before positron emission tomography imaging. Mice were injected intravenously with 0.1 ml of F-18 FDG (3.7 × 10 ⁵ Bq, 100 μCi) and positron emission tomography was performed 30 minutes later to obtain an image. Then, after 24 hours, 400 μg of pioglitazone was dissolved in 100 μl of a DMSO solution diluted with saline, and then injected intraperitoneally into mice, and 30 minutes later, intravenously injected with 0.1 mL of F-18 FDG (3.7 × 10 ⁵ Bq, 100 μCi). Positron emission tomography was then performed to obtain an image.

The results are shown in FIG. 5 and Table 5.

F-18 FDG in malignant tumors (lung cancer) lesions and inflammatory lesions obtained by injecting pioglitazone and F-18 FDG after 24 hours after F-18 FDG injection into malignant tumors (lung cancer) and inflammation-induced mice Intake of Intake of F-18 FDG (% ID / g) Intake of F-18 FDG
Increase Before pioglitazone injection After pioglitazone injection Malignant tumor (lung cancer) lesion 3.47 3.97 14.4% Inflammatory lesions 3.93 3.95 0.51%

※% ID / g: The percentage of F-18 FDG radiation present per unit weight of the tissue or organ to be measured, based on the actual dose of F-18 FDG.

As shown in FIG. 5 and Table 5, the intake of F-18 FDG in malignant tumor (lung cancer) lesions was increased by about 14.4% after injection compared to before pioglitazone injection, but the intake of F-18 FDG in inflammatory lesions was higher than before pioglitazone injection. About 0.51% increase after infusion. In addition, positron emission tomography images showed a clear visual increase in malignant tumors (lung cancer) lesions after injection compared to before pioglitazone injection, but there was almost no difference in inflammatory lesions. Therefore, it can be seen that there is a difference in the intake of F-18 FDG by pioglitazone in malignant tumor lesions and inflammatory lesions.

Example  6  : In malignant tumors (breast cancer) and inflammatory lesions In pioglitazone  By F-18 FDG Changes in intake

In order to observe changes in the intake of F-18 FDG by pioglitazone in mice with both malignant (breast cancer) lesions and inflammatory lesions, breast cancer cells (MDA) instead of lung cancer cells (A549) in the right hind limb of Example 4 were observed. Positron emission tomography images were obtained in the same manner as in Example 4, except that malignant tumors (breast cancer) were formed by injection.

The results are shown in Figure 6 and Table 6.

Malignant tumors (breast cancer) and F-18 FDG in the malignant tumors (breast cancer) lesions and inflammatory lesions obtained by injecting pioglitazone and F-18 FDG after 2 hours after F-18 FDG injection into the mice with inflammation. Intake of Intake of F-18 FDG (% ID / g) Intake of F-18 FDG
Increase Before pioglitazone injection After pioglitazone injection Malignant tumor (breast cancer) lesion 10.52 10.28 -2.3% Inflammatory lesions 8.39 7.3 -13.0%

※% ID / g: The percentage of F-18 FDG radiation present per unit weight of the tissue or organ to be measured, based on the actual dose of F-18 FDG.

As shown in Figure 6 and Table 6, the intake of F-18 FDG in malignant tumors (breast cancer) lesions and inflammatory lesions was reduced both before and after pioglitazone injection, in particular the intake of F-18 FDG in inflammatory lesions was malignant tumor ( Breast cancer), which was about 5.6 times lower than that of the lesion by 13%. In addition, positron emission tomography images showed significant visual changes in malignant tumors (breast cancer) after injection compared to before pioglitazone injection, but there was almost no difference in inflammatory lesions. Therefore, it can be seen that there is a difference in the intake of F-18 FDG by pioglitazone in malignant tumor lesions and inflammatory lesions.

Example  7  : In malignant tumors (breast cancer) and inflammatory lesions In pioglitazone  By F-18 FDG Changes in intake

Example to observe the change in intake of F-18 FDG by pioglitazone after excluding the effect of F-18 FDG taken before pioglitazone injection in mice with both malignant (breast cancer) lesions and inflammatory lesions 5, the positron emission tomography image was obtained in the same manner as in Example 5 except that breast cancer cells (MDA-MB-231) were injected into the right hind limb of the mouse instead of lung cancer cells (A549) to form malignant tumors (breast cancer). Got it.

The results are shown in Figure 7 and Table 7.

F-18 FDG in malignant tumors (breast cancer) lesions and inflammatory lesions obtained by injection of F-18 FDG into malignant tumors (breast cancer) and inflammation-induced mice 24 hours after pioglitazone injection and F-18 FDG injection Intake of Intake of F-18 FDG (% ID / g) Intake of F-18 FDG
Increase Before pioglitazone injection After pioglitazone injection Malignant tumor (breast cancer) lesion 8.18 10.57 29.2% Inflammatory lesions 5.10 3.86 -24.3%

※% ID / g: The percentage of F-18 FDG radiation present per unit weight of the tissue or organ to be measured, based on the actual dose of F-18 FDG.

As shown in Figure 7 and Table 7, the intake of F-18 FDG in malignant tumors (breast cancer) lesions increased about 29.2% after injection compared to before pioglitazone injection, the intake of F-18 FDG in inflammatory lesions compared to before pioglitazone injection After infusion, it was greatly reduced to about 24.3%. In addition, positron emission tomography images showed significant visual changes in malignant tumors (breast cancer) after injection compared to before pioglitazone injection, but there was almost no difference in inflammatory lesions. Therefore, it can be seen that there is a difference in the intake of F-18 FDG by pioglitazone in malignant tumor lesions and inflammatory lesions.

Claims (3)

F-18 in malignant tumor lesions by treatment of pioglitazone with F-18 fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) was relatively increased as compared to uptake of FDG to -18 intake of F-18 FDG in inflammatory lesions, positron emission tomography imaging when to distinguish malignant tumors and inflammatory lesions, including the step of selectively screening the cancer, Method of providing information for selective diagnosis of malignant tumors. The method of claim 1, wherein the selective selection of the malignant tumors is performed by identifying cancer lesions in tuberculosis patients, distinguishing between lymph node involvement and lymphadenitis in lymphoma patients, identifying lymph node metastasis in cancer patients, recurrence after cancer patient surgery and the presence of residual cancer lesions. A method for providing information for the selective diagnosis of malignant tumors, characterized in that it is applied to the distinction from inflammatory lesions after surgery or to residual cancer or recurrence after radiotherapy in cancer patients and inflammatory lesions by radiation therapy. According to claim 1, wherein the tumor is oral cancer, cerebrospinal tumor, head and neck cancer, lung cancer, breast cancer, thymic tumor, mesothelioma, esophageal cancer, gastric cancer, colon cancer, liver cancer, pancreatic cancer, biliary tract cancer, kidney cancer, bladder cancer, prostate cancer, testicular cancer, reproductive cancer Cell tumor, ovarian cancer, cervical cancer, endometrial cancer, lymphoma, acute leukemia, chronic leukemia, multiple myeloma, sarcoma, malignant melanoma and skin cancer, characterized in that at least one selected from the group consisting of How to Provide Information.

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