KR20130068817A - Method for diagnosing selectively malignant tumor by differentiating malignant tumor and inflammation in f-18 fdg positron emission tomography using pioglitazone - Google Patents
Method for diagnosing selectively malignant tumor by differentiating malignant tumor and inflammation in f-18 fdg positron emission tomography using pioglitazone Download PDFInfo
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Abstract
Description
본 발명은 Ｆ-18 ＦＤＧ 양전자방출단층촬영에서 피오글리타존의 처리에 의해 악성 종양과 염증 병변을 구분하여 악성 종양을 선택적으로 진단하는 방법에 관한 것이다.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.
의료기술적 측면에서 악성 종양환자를 검진하거나 수술시 악성 종양환자의 악성 종양 병소를 정확히 찾는 것은 환자의 상태를 정확히 진단하거나 수술범위를 결정하는데 있어서 매우 중요하다. 또한 악성 종양이 아닌 다른 병변 부위를 확인하는 것도 환자의 예후에 매우 중요한 영향을 미친다.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.
최근 질병의 진단에 있어서, 수술을 하지 않고 몸속 환부를 찾아내는 방법으로 형광, 생물발광((bioluminescence), SPECT(single photon emission computed tomography), 컴퓨터단층촬영(computed tomography, CT), 자기공명단층촬영 (magnetic resonance imaging, MRI), 양전자방출단층촬영(positron emission tomography, PET), 초음파 등 다양한 분자 영상 기법이 활용되고 있다. 분자영상이란 분자생물학, 세포생물학을 비-침습적 생체영상(non-invasive in vivo imaging)으로 응용하여 생채 내에서 일어나는 분자 수준의 변화를 영상화하는 기법으로, 분자세포생물학과 첨단영상기술이 발전하여 접목된 새로운 분야이다.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.
이러한 분자 영상 기법은 암의 조기 진단, 약제 개발, 항암치료, 유전자-줄기세포 치료의 모니터링 등에 활용된다. 또한, 분자 영상은 생체 조직을 손상시키지 않고 반복적으로 영상화할 수 있어 세포 수준의 기초연구를 임상에 쓰일 수 있게 하는 중개 연구(translational research)의 중요한 부분이다.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.
분자 영상 기법들 중 양전자방출단층촬영(PET)은 양전자를 방출하는 방사성 의약품을 이용하여 인체에 대한 생리·화학적 및 기능적 영상을 3차원으로 나타낼 수 있는 핵의학 검사 방법 중 하나로, 현재 각종 암을 진단하는데 주로 활용되고 있으며, 암에 대한 감별 진단, 병기 설정, 재발 평가, 치료 효과 판정 등에 유용한 검사로 알려져 있다. 이외에도 양전자방출단층촬영을 이용하여 심장 질환, 뇌 질환 및 뇌 기능 평가를 위한 수용체 영상이나 대사 영상도 얻을 수 있다.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.
양전자방출단층촬영용 방사성 동위원소는 생물학적 주요 구성 성분인 불소 (F-18), 탄소(C-11), 산소(O-15), 질소(N-13) 등으로, 화학적 성질의 변화없이 체내 성분대사, 약물대사, 수용체 영상화가 가능하다. 또한, 이들 방사성 동위원소를 이용하여 특정 생리·화학적 및 기능적 변화를 반영하는 추적자(tracer)인 방사성 의약품을 만들 수 있다. 가장 많이 이용되고 있는 방사성 의약품으로는 F-18 FDG (fluoro-2-deoxy-D-glucose)가 있으며, 이는 포도당 유사 물질이어서 이를 주사하면 몸 안에서 암과 같이 포도당 대사가 항진된 병변에 많이 모이게 된다. 악성 종양세포는 정상세포 혹은 양성 종양세포에 비해 더 많은 에너지가 필요하게 되어 에너지원으로 상당히 많은 양의 포도당을 섭취하게 된다. 악성 종양세포가 포도당 섭취를 증가시키는 기전은 악성 종양 세포의 세포막에서 포도당 수송체(glucose transporter)의 발현이 증가되고, 세포질 내에서는 포도당을 에너지로 이용하는데 필요한 헥소키나제(hexokinase)의 발현이 증가되어 악성 종양에서 섭취효과가 나타나게 된다. 또한, FDG는 포도당 유사체로, 세포막의 포도당 수송체를 통하여 세포 내로 섭취되며, 헥소키나제의 기질로 이용되어 인산화된다. 그러나, 다음 단계인 해당과정(glycolysis)이 진행되지 않고 인산화 상태로 세포 내에 축적되기 때문에 선명한 영상을 얻을 수 있다. 또한, 포도당과 달리 신장의 근위곡세관(proximal convoluted tubule)에서 재흡수가 되지 않아 비뇨기계를 통해 체외로 배출된다.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.
따라서, 질병의 진단에 사용되는 영상 기법들 중 양전자방출단층촬영 검사, 특히 F-18 FDG를 이용한 양전자방출단층촬영 검사는 우리나라뿐만 아니라 전 세계적으로 악성 종양환자를 진단하고, 병기를 결정하며, 치료 방침과 예후 그리고 재발 여부 등의 결정 등 광범위한 영역에 이용되고 있으며, 질병의 진단 정확도가 매우 높은 것으로 알려져 있다.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.
그러나, F-18 FDG의 섭취는 악성 종양세포에서 많이 이루어지지만, 염증 병변에 있는 대식 세포 또는 염증세포에서도 섭취되기 때문에 두 병변이 양전자방출단층촬영 영상에서 큰 차이 없이 비슷하게 관찰된다. 즉, 이러한 FDG 섭취의 증가가 악성 종양에서뿐만 아니라 정상적인 상태가 아닌 염증환부에서도 일어나게 되어 이러한 병변에서 F-18 FDG의 섭취가 악성 종양의 전위에 의한 것인지 또는 단순 염증에 의한 포도당 섭취에 의한 것인지는 영상 판독을 통해 정확하게 진단하기 어렵다. 따라서, 악성 종양환자나 염증환자의 진단에 종종 어려움을 겪는다. 그러나, 악성 종양과 염증의 치료법은 전혀 상이하므로, 악성 종양과 염증을 정확히 구분하는 것이 임상에서는 매우 중요하다. 따라서, F-18 FDG를 이용한 양전자방출단층촬영 검사 시 악성 종양만 선택적으로 정확하게 진단할 수 있는 방법의 개발이 필요하다.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.
한편, PPAR-γ(peroxisome proliferator-activated receptor-γ)는 리간드 의존 전이요소로, 주로 지방조직에서 발현되며, 결장, 신장, 근육, 간에도 소량 존재하고, 지방조직 생성과 많은 관련이 있다. 또한, PPAR-γ는 글루코오스 대사와 세포 성장 과정에서 중요한 조절작용을 하는 것으로 잘 알려져 있으며, 단핵구 (monocytes)/대식 세포(macrophages)와 같은 면역조직 세포에서 발견되는 중요한 면역조절제로 염증과정에서 사이토카인을 저해하여 항염증 효과가 있음이 보고되어 있다. 또한, PPAR-γ는 당뇨병성 신증의 진행을 억제할 수 있다고 보고되어 있다.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.
상기한 바와 같이, PPAR-γ 작용물질의 항염증 효과 및 항당뇨 효과에 대해서는 알려져 있지만, PPAR-γ 작용물질을 F-18 FDG를 이용한 양전자방출단층촬영에 사용된 예는 거의 없으며, 이에 대한 연구도 미미한 상태이다.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.
따라서, PPAR-γ 작용물질의 항염증 효과를 이용하여 F-18 FDG 양전자방출단층촬영 검사를 수행하면, 악성 종양과 염증 진단 시 PPAR-γ 작용물질에 의해 악성 종양 병변에서만 F-18 FDG 섭취를 증가시켜 악성 종양에 대해 선택적으로 진단할 수 있을 것으로 생각된다.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.
본 발명자들은 F-18 FDG 양전자방출단층촬영 검사 시 악성 종양과 염증 병변을 구분하여 악성 종양 병변만 선택적으로 진단할 수 있는 방법에 대해 연구하던 중, F-18 FDG 양전자방출단층촬영에서 피오글리타존을 처리한 경우 피오글리타존을 처리하지 않은 경우에 비해 악성 종양 병변에서만 F-18 FDG의 섭취량을 증가시키고, 염증 병변에서는 F-18 FDG의 섭취량을 약간 증가시키거나 감소시켜 양전자방출단층촬영 영상 진단 시 악성 종양과 염증 병변을 구분하여 악성 종양 병변만 선택적으로 진단할 수 있음을 확인하고, 본 발명을 완성하였다.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.
따라서, 본 발명은 피오글리타존을 이용한 Ｆ-18 ＦＤＧ 양전자방출단층촬영에서 악성 종양과 염증 병변을 구분하여 악성 종양을 선택적으로 진단하는 방법을 제공하고자 한다.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.
본 발명은 피오글리타존을 이용한 Ｆ-18 ＦＤＧ 양전자방출단층촬영에서 악성 종양과 염증 병변을 구분하여 악성 종양을 선택적으로 진단하는 방법을 제공한다.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.
이하, 본 발명에 대해 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명에 따른 피오글리타존을 이용한 F-18 FDG 양전자방출단층촬영에서 악성 종양을 선택적으로 진단하는 방법은, F-18 FDG 양전자방출단층촬영에서 피오글리타존을 처리한 경우 피오글리타존을 처리하지 않은 경우에 비해 악성 종양 병변에서만 F-18 FDG의 섭취량을 증가시키고, 염증 병변에서는 F-18 FDG의 섭취량을 약간 증가시키거나 감소시키는 것을 특징으로 한다.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.
본 발명에 따른 피오글리타존은, 악성 종양 세포에서 GLUT1 단백질의 발현과 GLUT1/Actin 값을 높게 나타내고, 대식 세포(RAW 264.7)에서는 GLUT1 단백질의 발현과 GLUT1/Actin 값을 낮게 나타냄으로써, 악성 종양세포에서 글루코오스 농도가 낮음을 알 수 있다. 따라서, 피오글리타존으로 처리된 악성 종양 세포에 F-18 FDG를 처리할 경우 F-18 FDG의 섭취량이 증가할 것으로 예측할 수 있다.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.
또한, 본 발명에 따른 피오글리타존은, 악성 종양 병변에서 F-18 FDG의 섭취량을 현저히 증가시키지만, 정상세포에서는 F-18 FDG의 섭취량을 약간 증가시키고, 양전자방출단층촬영 영상에서는 악성 종양 병변에서 선명한 영상적 변화를 보인다.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.
또한, 본 발명에 따른 피오글리타존은, 악성 종양 병변과 염증 병변이 모두 존재하는 마우스의 악성 종양 병변에서 F-18 FDG의 섭취량을 현저히 증가시키고, 염증 병변에서는 F-18 FDG의 섭취량을 약간 증가시키거나 감소시킨다. 또한, 본 발명의 피오글리타존은 양전자방출단층촬영 영상에서 악성 종양 병변에서만 영상적 변화가 나타나고, 염증 병변에서는 영상적 변화가 거의 나타나지 않는다. 따라서, 악성 종양 병변과 염증 병변에서 피오글리타존에 의해 F-18 FDG의 섭취량에 차이가 있음을 알 수 있다.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.
상기한 바와 같이, 본 발명에 따른 피오글리타존은, 악성 종양 병변에서는 F-18 FDG의 섭취량을 현저히 증가시키고, 염증 병변에서는 F-18 FDG의 섭취량을 약간 증가시키거나 감소시킴으로써, 양전자방출단층촬영 영상 진단 시 악성 종양과 염증을 구분하여 악성 종양 병변만 선택적으로 진단할 수 있다.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.
따라서, 본 발명에 따른 피오글리타존을 이용한 F-18 FDG 양전자방출단층촬영에서 악성 종양을 선택적으로 진단하는 방법은, 결핵 환자에게서 암 병변 확인, 림프종 환자에게서 림프절 침범과 림프절염과의 구분, 암 환자에게서 림프절 전이 유무 확인, 암환자 수술 후 재발 및 잔류암 병변 존재와 수술 후 염증 병변과의 구분, 또는 암환자에게서 방사선요법 시행 후 잔류암 또는 재발암과 방사선 치료에 의한 염증 병변과의 구분 등에 적용 가능하다.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. .
본 발명에서 악성 종양은 구강암, 뇌척수종양, 두경부암, 폐암, 유방암, 흉선종, 중피종, 식도암, 위암, 대장암, 간암, 췌장암, 담도암, 신장암, 방광암, 전립선암, 고환암, 생식세포종, 난소암, 자궁 경부암, 자궁 내막암, 림프종, 급성 백혈병, 만성 백혈병, 다발성 골수종, 육종, 악성 흑색종, 피부암을 포함하나, 이에 한정되지 않는다.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.
본 발명에 따른 피오글리타존은 악성 종양 병변에서는 F-18 FDG의 섭취량을 현저히 증가시키고, 염증 병변에서는 F-18 FDG의 섭취량을 약간 증가시키거나 감소시킴으로써, 양전자방출단층촬영 영상 진단 시 악성 종양과 염증을 구분하여 악성 종양 병변만 선택적으로 진단할 수 있다.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.
도 1은 악성 종양 세포에서 피오글리타존 농도에 따른 글루코오스 수송 단백질(GLUT1)의 발현 정도와 GLUT1/Actin 값을 나타낸 도이다[구강암 세포(KB), 유방암 세포(MDA-MB-231), 폐암 세포(A549), 대식 세포(RAW 264.7)].
도 2는 악성 종양(폐암)이 유발된 마우스에 F-18 FDG를 주입하고 1시간 경과한 다음 피오글리타존을 주입하고 F-18 FDG를 주입하여 얻은 양전자방출단층촬영 영상을 나타낸 도이다(화살표는 악성 종양 병변을 가리킴).
도 3은 악성 종양(폐암)이 유발된 마우스에 F-18 FDG를 주입하고 24시간 경과한 다음 피오글리타존을 주입하고 F-18 FDG를 주입하여 얻은 양전자방출단층촬영 영상을 나타낸 도이다(화살표는 악성 종양 병변을 가리킴).
도 4는 악성 종양(폐암)과 염증이 유발된 마우스에 F-18 FDG를 주입하고 2시간 경과한 다음 피오글리타존을 주입하고 F-18 FDG를 주입하여 얻은 양전자방출단층촬영 영상을 나타낸 도이다(점선 원은 악성 종양 병변 및 염증 병변을 나타낸 것임).
도 5는 악성 종양(폐암)과 염증이 유발된 마우스에 F-18 FDG를 주입하고 24시간 경과한 다음 피오글리타존을 주입하고 F-18 FDG를 주입하여 얻은 양전자방출단층촬영 영상을 나타낸 도이다(점선 원은 악성 종양 병변 및 염증 병변을 나타낸 것임).
도 6은 악성 종양(유방암)과 염증이 유발된 마우스에 F-18 FDG를 주입하고 2시간 경과한 다음 피오글리타존을 주입하고 F-18 FDG를 주입하여 얻은 양전자방출단층촬영 영상을 나타낸 도이다(점선 원은 악성 종양 병변 및 염증 병변을 나타낸 것임).
도 7은 악성 종양(유방암)과 염증이 유발된 마우스에 F-18 FDG를 주입하고 24시간 경과한 다음 피오글리타존을 주입하고 F-18 FDG를 주입하여 얻은 양전자방출단층촬영 영상을 나타낸 도이다(점선 원은 악성 종양 병변 및 염증 병변을 나타낸 것임).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).
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.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.
실시예Example 1 One : 악성 종양 세포에서 In malignant tumor cells 피오글리타존이Fioglitazone 글루코오스 섭취에 미치는 영향 Effect on Glucose Intake
악성 종양 세포에서 피오글리타존이 글루코오스 섭취에 미치는 영향을 확인하기 위하여, 하기와 같은 실험을 수행하였다.To determine the effect of pioglitazone on glucose uptake in malignant tumor cells, the following experiment was performed.
구체적으로는, 구강암 세포(KB), 유방암 세포(MDA-MB-231), 폐암 세포 (A549), 대식 세포(RAW 264.7)를 각각 6㎝ 배양접시에 1×106의 세포수로 접종하고, 각 세포를 CO2 배양기에서 10% FBS(fetal bovine serum)와 1% 항생제가 첨가된 RPMI-1640 배양 배지에서 12시간 동안 배양하였다. 그 다음, 각 세포에 피오글리타존을 농도별(10, 50, 100, 150 μM)로 처리하고 1시간 동안 CO2 배양기에서 배양하였다. 피오글리타존이 처리된 배양배지를 걷어내고, 각 세포를 인산염 완충액(pH 7.4)으로 2번 세척한 다음, 20mM Tris-HCl(pH 7.4), 2mM EDTA, 1mM Na3VO4(sodium orthovanadate), 0.1mM PMSF(phenylmethylsulfonyl fluoride) 및 단백질분해효소 저해제가 함유된 용해 완충액(lysis buffer)을 이용하여 배양접시에 붙어있는 세포을 모아서 세포 내 단백질을 추출하였다. 추출된 단백질을 정량하고, 그 중 35㎍을 취해 아크릴아미드 겔(웨스턴 블롯 시 사용하는 전기영동 겔)에 로딩하여 SDS-PAGE를 행하였다. 전기영동 후 겔 내에 있는 단백질을 전이 과정을 통해 PVDF 막으로 옮기고, PVDF 막에 있는 단백질 밴드만 표면에 노출되도록 5% 탈지분유 용액(차단 용액)에서 1시간 동안 반응시켰다. 그 다음, 인산염 완충액(pH 7.4)으로 세척하고 토끼에서 생성된 GLUT1에 대한 1차 IgG 항체를 1:500으로 희석하여 PVDF 막에 처리하고 4℃에서 12시간 이상 반응시켰다. PVDF 막을 인산염 완충액(pH 7.4)으로 세척하여 막에 남아있는 1차 항체를 제거하고, HRP(horseradish peroxidase)가 결합된 염소에서 생성된 항-토끼 IgG 2차 항체를 1:2500으로 희석하여 PVDF 막에 처리하고 실온에서 1시간 동안 반응시켰다. PVDF 막을 인산염 완충액(pH 7.4)으로 세척하여 막에 남아있는 2차 항체를 제거하고, ECL(enhanced chemiluminescence) 용액 검출 키트와 발광 영상 분석 장비(luminescent image analyzer, LAS-3000, Fuji Film, Japan)를 이용하여 항체와 결합한 GLUT1 단백질의 발현 정도를 확인하였다. GLUT1 단백질은 글루코오스 농도가 높으면 낮게 발현되고, 글루코오스 농도가 낮으면 높게 발현된다고 알려져 있다.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.
결과는 도 1 및 표 1에 나타내었다.The results are shown in Figure 1 and Table 1.
도 1 및 표 1에 나타난 바와 같이, 구강암 세포(KB), 유방암 세포(MDA-MB-231), 폐암 세포(A549)에서 피오글리타존 처리에 의해 GLUT1 단백질의 발현과 GLUT1/Actin 값이 높게 나타났다. 이에 반해, 대식 세포(RAW 264.7)에서는 GLUT1 단백질의 발현과 GLUT1/Actin 값이 낮게 나타났다. 따라서, 악성 종양세포에서 글루코오스 농도가 낮음을 알 수 있으며, 이러한 결과에 의해 피오글리타존으로 처리된 악성 종양 세포에 F-18 FDG를 처리할 경우 F-18 FDG의 섭취량이 증가할 것으로 예측할 수 있다.
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.
실시예Example 2 2 : 악성 종양(폐암) 병변에서 : In malignant tumor (lung cancer) lesion 피오글리타존에In pioglitazone 의한 F-18 By F-18 FDGFDG 의 섭취량 변화 관찰Changes in intake
악성 종양(폐암) 병변에서 피오글리타존에 의한 F-18 FDG의 섭취량 변화를 관찰하기 위하여, 하기와 같은 실험을 수행하였다.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.
구체적으로는, 4~5 주령의 마우스(Japan SLC, Inc.)의 오른쪽 뒷다리에 폐암 세포(A549)를 주입하여 악성 종양(폐암)을 형성하고 1㎝ 정도까지 배양하여 이종이식한 마우스를 준비한 후, 양전자방출단층촬영(PET) 영상 촬영 전 12시간 전부터 금식시켰다. 마우스에 F-18 FDG (3.7×105 Bq, 100μCi) 0.1㎖를 정맥 주사하고 30분 후에 양전자방출단층촬영을 수행하여 영상을 얻었다. 그 다음, 1시간 경과 후 식염수로 희석시킨 DMSO 용액 100㎕에 피오글리타존 400㎍을 녹인 후, 이를 마우스에 복강내 주사하고 30분 후에 F-18 FDG (3.7×105 Bq, 100μCi) 0.1㎖를 정맥 주사한 후 양전자방출단층촬영을 수행하여 영상을 얻었다. 이러한 실험 조건은 실제로 임상 양전자방출단층촬영 조건을 고려하여 프로토콜을 작성하였으며, 피오글리타존을 사람에게 적용시킬 때의 조건을 고려하여 실험조건을 결정하였다. 또한, 피오글리타존의 주입량 또한 당뇨병 환자에게 처방하는 1회 복용량을 기준으로 마우스 중량을 고려하여 결정하였다.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.
결과는 도 2 및 표 2에 나타내었다.The results are shown in Figure 2 and Table 2.
증가량Intake of F-18 FDG
Increase
※ %ID/g: F-18 FDG의 실제 주입한 방사선 양에 대해 측정하고자 하는 조직이나 기관의 단위 무게당 존재하는 F-18 FDG의 방사능 양을 백분율로 나타낸 것.
※% 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.
도 2 및 표 2에 나타난 바와 같이, 악성 종양(폐암) 병변에서 F-18 FDG의 섭취량은 피오글리타존 주입 전에 비해 주입 후에 약 20.5% 증가하였으며, 양전자방출단층촬영 영상에서도 피오글리타존 주입 전에 비해 주입 후에 악성 종양(폐암) 병변에서 선명한 영상적 증가를 확인하였다. 따라서, 악성 종양 병변에서 피오글리타존에 의해 F-18 FDG의 섭취량이 선택적으로 증가함을 알 수 있다.
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.
실시예Example 3 3 : 악성 종양(폐암) 병변에서 : In malignant tumor (lung cancer) lesion 피오글리타존에In pioglitazone 의한 F-18 By F-18 FDGFDG 의 섭취량 변화 관찰Changes in intake
악성 종양(폐암) 병변에서 피오글리타존 주입 전에 섭취된 F-18 FDG에 의한 영향을 배제시킨 후, 피오글리타존에 의한 F-18 FDG의 섭취량 변화를 관찰하기 위하여, 하기와 같은 실험을 수행하였다.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.
구체적으로는, 4~5 주령의 마우스(Japan SLC, Inc.)의 오른쪽 뒷다리에 폐암 세포(A549)를 주입하여 악성 종양(폐암)을 형성하고 1㎝ 정도까지 배양하여 이종이식한 마우스를 준비한 후, 양전자방출단층촬영 영상 촬영 전 12시간 전부터 금식시켰다. 마우스에 F-18 FDG (3.7×105 Bq, 100μCi) 0.1㎖를 정맥 주사하고 30분 후에 양전자방출단층촬영을 수행하여 영상을 얻었다. 그 다음, F-18 FDG에서 나오는 방사능의 활성이 소멸되어 양전자방출단층촬영 영상에 영향이 없는 시간인 24시간이 경과한 후 식염수로 희석시킨 DMSO 용액 100㎕에 피오글리타존 400㎍을 녹인 후, 이를 마우스에 복강내 주사하고 30분 후에 F-18 FDG (3.7×105 Bq, 100μCi) 0.1㎖를 정맥 주사한 후 양전자방출단층촬영을 수행하여 영상을 얻었다. 방사성 동위원소는 반감기가 5~6회 정도 지나면 활성이 완전히 소멸되었다고 판단할 수 있으므로, 24시간이 지나면 반감기가 2시간인 F-18 FDG의 활성은 마우스의 몸에서 모두 사라졌다고 판단할 수 있다.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
결과는 도 3 및 표 3에 나타내었다.The results are shown in Figure 3 and Table 3.
증가량Intake of F-18 FDG
Increase
※ %ID/g: F-18 FDG의 실제 주입한 방사선 양에 대해 측정하고자 하는 조직이나 기관의 단위 무게당 존재하는 F-18 FDG의 방사능 양을 백분율로 나타낸 것.
※% 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.
도 3 및 표 3에 나타난 바와 같이, 악성 종양(폐암) 병변에서 F-18 FDG의 섭취량은 피오글리타존 주입 전에 비해 주입 후에 약 83.2% 증가하였으며, 정상세포에서는 피오글리타존 주입 전과 후에 F-18 FDG의 섭취량이 6.3%로 약간 증가하였다. 또한, 양전자방출단층촬영 영상에서도 피오글리타존 주입 전에 비해 주입 후에 악성 종양(폐암) 병변에서 선명한 영상적 증가를 확인하였다. 따라서, 악성 종양 병변에서 피오글리타존에 의해 F-18 FDG의 섭취량이 선택적으로 증가함을 알 수 있다.
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.
실시예Example 4 4 : 악성 종양(폐암) 및 염증 병변에서 : In malignant tumors (lung cancer) and inflammatory lesions 피오글리타존에In pioglitazone 의한 F-18 FDG의 섭취량 변화 관찰 Changes in intake of F-18 FDG
악성 종양(폐암) 병변과 염증 병변이 모두 존재하는 마우스에서 피오글리타존에 의한 F-18 FDG의 섭취량 변화를 관찰하기 위하여, 하기와 같은 실험을 수행하였다.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.
구체적으로는, 4~5 주령의 마우스(Japan SLC, Inc.)의 오른쪽 뒷다리에 폐암 세포(A549)를 주입하여 악성 종양(폐암)을 형성하고 0.8㎝ 정도까지 배양한 다음, 마우스의 왼쪽 뒷다리에 테레빈유(turpentine oil) 100㎕를 주입하여 염증을 유발하여 악성 종양(폐암)과 염증이 모두 존재하는 이종이식된 마우스를 준비하였다. 양전자방출단층촬영 영상 촬영 전 12시간 전부터 이종이식한 마우스를 금식시켰다. 마우스에 F-18 FDG (3.7×105 Bq, 100μCi) 0.1㎖를 정맥 주사하고 30분 후에 양전자방출단층촬영을 수행하여 영상을 얻었다. 그 다음, 1회 반감기인 2시간 후에 식염수로 희석시킨 DMSO 용액 100㎕에 피오글리타존 400㎍을 녹인 후, 이를 마우스에 복강내 주사하고 30분 후에 F-18 FDG (3.7×105 Bq, 100μCi) 0.1㎖를 정맥 주사한 후 양전자방출단층촬영을 수행하여 영상을 얻었다.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.
결과는 도 4 및 표 4에 나타내었다.The results are shown in Figure 4 and Table 4.
증가량Intake of F-18 FDG
Increase
※ %ID/g: F-18 FDG의 실제 주입한 방사선 양에 대해 측정하고자 하는 조직이나 기관의 단위 무게당 존재하는 F-18 FDG의 방사능 양을 백분율로 나타낸 것.
※% 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.
도 4 및 표 4에 나타난 바와 같이, 악성 종양(폐암) 병변과 염증 병변에서 F-18 FDG의 섭취량은 피오글리타존 주입 전과 주입 후에 모두 감소하였으며, 특히 염증 병변에서 F-18 FDG의 섭취량은 악성 종양(폐암) 병변에 비해 약 2배인 15% 정도 감소하였다. 또한, 양전자방출단층촬영 영상에서도 피오글리타존 주입 전에 비해 주입 후에 악성 종양(폐암) 병변에서 영상적 증가를 확인하였으나, 염증 병변에서는 거의 차이가 없었다. 따라서, 악성 종양 병변과 염증 병변에서 피오글리타존에 의해 F-18 FDG의 섭취량에 차이가 있음을 알 수 있다.
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.
실시예Example 5 5 : 악성 종양(폐암) 및 염증 병변에서 : In malignant tumors (lung cancer) and inflammatory lesions 피오글리타존에In pioglitazone 의한 F-18 FDG의 섭취량 변화 관찰 Changes in intake of F-18 FDG
악성 종양(폐암) 병변과 염증 병변이 모두 존재하는 마우스에서 피오글리타존 주입 전에 섭취된 F-18 FDG에 의한 영향을 배제시킨 후, 피오글리타존에 의한 F-18 FDG의 섭취량 변화를 관찰하기 위하여, 하기와 같은 실험을 수행하였다.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.
구체적으로는, 4~5 주령의 마우스(Japan SLC, Inc.)의 오른쪽 뒷다리에 폐암 세포(A549)를 주입하여 악성 종양(폐암)을 형성하고 0.8㎝ 정도까지 배양한 다음, 마우스의 왼쪽 뒷다리에 테레빈유(turpentine oil) 100㎕를 주입하여 염증을 유발하여 악성 종양(폐암)과 염증이 모두 존재하는 이종이식된 마우스를 준비하였다. 양전자방출단층촬영 영상 촬영 전 12시간 전부터 이종이식한 마우스를 금식시켰다. 마우스에 F-18 FDG (3.7×105 Bq, 100μCi) 0.1㎖를 정맥 주사하고 30분 후에 양전자방출단층촬영을 수행하여 영상을 얻었다. 그 다음, 24시간 후에 식염수로 희석시킨 DMSO 용액 100㎕에 피오글리타존 400㎍을 녹인 후, 이를 마우스에 복강내 주사하고 30분 후에 F-18 FDG (3.7×105 Bq, 100μCi) 0.1㎖를 정맥 주사한 후 양전자방출단층촬영을 수행하여 영상을 얻었다.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.
결과는 도 5 및 표 5에 나타내었다.The results are shown in FIG. 5 and Table 5.
증가량Intake of F-18 FDG
Increase
※ %ID/g: F-18 FDG의 실제 주입한 방사선 양에 대해 측정하고자 하는 조직이나 기관의 단위 무게당 존재하는 F-18 FDG의 방사능 양을 백분율로 나타낸 것.
※% 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.
도 5 및 표 5에 나타난 바와 같이, 악성 종양(폐암) 병변에서 F-18 FDG의 섭취량은 피오글리타존 주입 전에 비해 주입 후에 약 14.4% 증가하였으나, 염증 병변에서 F-18 FDG의 섭취량은 피오글리타존 주입 전에 비해 주입 후에 약 0.51% 증가하였다. 또한, 양전자방출단층촬영 영상에서도 피오글리타존 주입 전에 비해 주입 후에 악성 종양(폐암) 병변에서 뚜렷한 영상적 증가를 확인하였으나, 염증 병변에서는 거의 차이가 없었다. 따라서, 악성 종양 병변과 염증 병변에서 피오글리타존에 의해 F-18 FDG의 섭취량에 차이가 있음을 알 수 있다.
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.
실시예Example 6 6 : 악성 종양(유방암) 및 염증 병변에서 : In malignant tumors (breast cancer) and inflammatory lesions 피오글리타존에In pioglitazone 의한 F-18 By F-18 FDGFDG 의 섭취량 변화 관찰Changes in intake
악성 종양(유방암) 병변과 염증 병변이 모두 존재하는 마우스에서 피오글리타존에 의한 F-18 FDG의 섭취량 변화를 관찰하기 위하여, 상기 실시예 4에서 마우스의 오른쪽 뒷다리에 폐암 세포(A549) 대신 유방암 세포(MDA-MB-231)를 주입하여 악성 종양(유방암)을 형성한 것을 제외하고는 실시예 4와 동일하게 하여 양전자방출단층촬영 영상을 얻었다.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.
결과는 도 6 및 표 6에 나타내었다.The results are shown in Figure 6 and Table 6.
증가량Intake of F-18 FDG
Increase
※ %ID/g: F-18 FDG의 실제 주입한 방사선 양에 대해 측정하고자 하는 조직이나 기관의 단위 무게당 존재하는 F-18 FDG의 방사능 양을 백분율로 나타낸 것.
※% 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.
도 6 및 표 6에 나타난 바와 같이, 악성 종양(유방암) 병변과 염증 병변에서 F-18 FDG의 섭취량은 피오글리타존 주입 전과 주입 후에 모두 감소하였으며, 특히 염증 병변에서 F-18 FDG의 섭취량은 악성 종양(유방암) 병변에 비해 약 5.6배인 13% 정도 감소하였다. 또한, 양전자방출단층촬영 영상에서도 피오글리타존 주입 전에 비해 주입 후에 악성 종양(유방암) 병변에서 뚜렷한 영상적 변화를 확인하였으나, 염증 병변에서는 거의 차이가 없었다. 따라서, 악성 종양 병변과 염증 병변에서 피오글리타존에 의해 F-18 FDG의 섭취량에 차이가 있음을 알 수 있다.
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.
실시예Example 7 7 : 악성 종양(유방암) 및 염증 병변에서 : In malignant tumors (breast cancer) and inflammatory lesions 피오글리타존에In pioglitazone 의한 F-18 By F-18 FDGFDG 의 섭취량 변화 관찰Changes in intake
악성 종양(유방암) 병변과 염증 병변이 모두 존재하는 마우스에서 피오글리타존 주입 전에 섭취된 F-18 FDG에 의한 영향을 배제시킨 후, 피오글리타존에 의한 F-18 FDG의 섭취량 변화를 관찰하기 위하여, 상기 실시예 5에서 마우스의 오른쪽 뒷다리에 폐암 세포(A549) 대신 유방암 세포(MDA-MB-231)를 주입하여 악성 종양(유방암)을 형성한 것을 제외하고는 실시예 5와 동일하게 하여 양전자방출단층촬영 영상을 얻었다.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.
결과는 도 7 및 표 7에 나타내었다.The results are shown in Figure 7 and Table 7.
증가량Intake of F-18 FDG
Increase
※ %ID/g: F-18 FDG의 실제 주입한 방사선 양에 대해 측정하고자 하는 조직이나 기관의 단위 무게당 존재하는 F-18 FDG의 방사능 양을 백분율로 나타낸 것.
※% 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.
도 7 및 표 7에 나타난 바와 같이, 악성 종양(유방암) 병변에서 F-18 FDG의 섭취량은 피오글리타존 주입 전에 비해 주입 후에 약 29.2% 증가하였으나, 염증 병변에서 F-18 FDG의 섭취량은 피오글리타존 주입 전에 비해 주입 후에 약 24.3% 정도로 크게 감소하였다. 또한, 양전자방출단층촬영 영상에서도 피오글리타존 주입 전에 비해 주입 후에 악성 종양(유방암) 병변에서 뚜렷한 영상적 변화를 확인하였으나, 염증 병변에서는 거의 차이가 없었다. 따라서, 악성 종양 병변과 염증 병변에서 피오글리타존에 의해 F-18 FDG의 섭취량에 차이가 있음을 알 수 있다.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.
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| KR20180128657A (en) * | 2017-05-24 | 2018-12-04 | 이화여자대학교 산학협력단 | Method for providing information of prediction for recurrence of breast cancer |
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| US11382586B2 (en) | 2013-09-25 | 2022-07-12 | Richard R. Black | Patient-specific analysis of raw positron emission tomography data |
| WO2016160538A1 (en) * | 2015-03-27 | 2016-10-06 | The Johns Hopkins University | Multi-level otsu for positron emission tomography (mo-pet) |
| KR20180128657A (en) * | 2017-05-24 | 2018-12-04 | 이화여자대학교 산학협력단 | Method for providing information of prediction for recurrence of breast cancer |
| KR20220048360A (en) * | 2020-10-12 | 2022-04-19 | 이화여자대학교 산학협력단 | Method for predicting the alteration of gut microbiota or the presence of intestinal inflammation by measuring the level of intestinal uptake of FDG |
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