TWI231215B - Treatment of cancer and other diseases by administration of positron-emitting radiopharmaceuticals - Google Patents
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相關申請案的交叉象考守辭 本申請案訴求2000年12月18曰歸檔的美國臨時專利申請系 列編號60/256,671之優先利益。今附上申請案内容全文供參 考0 服於在聯邦資助的研究下 所作的發明的權利的聲明 不適用的。 技術蓺圊 本發明係關於氟-18,氟-18標記的化合物,及其他同位 素標記的醫藥品及放射醫藥品在治療人類疾病,特別是治 療癌,上的新治療用途。 f景技藝 正子發射斷層照像(PET)是廣泛使用的造影技術。作pET 掃描時,給予要作掃描的病人正子發射化合物。此化合物 即疋位於身體各組織内。當化合物因正子發射而衰變時, 發射出的正子會遇到電子。在產生的511 keV的光子偶②士 of photons)時,即形成物質_反物質(matter_antimatt打)消滅現 象,此可藉PE丁掃描測出(1〇)。 一般情形下’正子發射化合物之半衰期較短,必須儘可 能在給予病人前的短時間内產生。放射性同位素是以回旋 加速器作放射處理生成,可以化學方法加於化合物中供給 予。由於氟-18( F)之半衰期較長達11〇分鐘,故氟_18同位 素是廣泛使用的加於化合物内供作PET掃描的放射性同位 素。這樣長的半衰期足以供給成標記化合物,給予病人, -4- 本紙張尺度適用中國國家標準(CNS) A4規格(2i〇x297公羡) 裝 訂Cross-References in Related Applications This application claims the priority benefit of US Provisional Patent Application Serial No. 60 / 256,671, filed December 18, 2000. The full text of the application is attached for reference. 0 Statement of the right to an invention made under federally funded research Not applicable. Technology 蓺 圊 The present invention relates to new therapeutic uses of fluorine-18, fluorine-18 labeled compounds, and other isotopically labeled pharmaceuticals and radiopharmaceuticals in the treatment of human diseases, especially cancer. f 景 技 positron emission tomography (PET) is a widely used imaging technique. For a pET scan, the patient is given a positron-emission compound. This compound is located in various tissues of the body. When a compound decays due to positron emission, the emitted positron encounters electrons. When the 511 keV photon couple (of the photons) is generated, the matter_antimatter (matter_antimatt) destruction phenomenon is formed, which can be measured by PE scanning (10). In general, the half-life of the positron-emitting compound is short and must be produced as short as possible before administration to the patient. Radioisotopes are generated by radiation treatment with a cyclotron, and can be chemically added to a compound and supplied. Since the half-life of fluorine-18 (F) is as long as 110 minutes, the fluorine-18 isotope is a widely used radioisotope added to compounds for PET scanning. Such a long half-life is sufficient to supply labeled compounds for patients. -4- This paper size applies the Chinese National Standard (CNS) A4 specification (2i0x297). Binding
線 1231215 A7 B7 五、發明説明(2 ) 並由病人的組織吸收。作PET掃描用的含氧-18的化合物的 一般劑量是3至20毫居里/50公斤體重。 作PET掃描廣泛使用的化合物是氟去氧葡萄糖(FdG)。 FDG用於測定及檢驗癌已有1〇年以上,在結腸直腸癌,肺 癌’黑色素瘤’淋巴瘤及乳癌的造影上較其他已有的造影 劑為優。FDG已用於癌,心臟病及神經病的代謝造影pET掃 描。 現已發現,藉了給予較診斷及造影目的所用劑量明顯為 高的放射標記的正子發射化合物治療疾病。本發明提供使 用正子發射化合物治療疾病的方法。 裝 本發明竭示 本發明提供-種治療病人疾,病’特収癌及相關疾病的 新穎方法。 於-具體實施例中’本發明提供—種治療病人疾病的方 法,包括給予此病人治療有效量的正子發射化合物。正子 發射化合物可含一或多個氟·18,碳·u,氮·13,或氧·15原 子》於另-具體實施例中,此正子發射化合物含一或多個 氧-18原子。 於一具體實施例中,此正子發射化合物為^心氟去氧葡 萄糖。於另一具體實施例中,,氣去氧葡萄糖是,8f_2•氣 -2-去氧葡萄糖。於又一具體實施例中,此正子發射化合Line 1231215 A7 B7 V. Description of the invention (2) and absorbed by the patient's tissue. A typical dose of an oxygen-18-containing compound for PET scanning is 3 to 20 mCi / 50 kg body weight. A widely used compound for PET scanning is fluorodeoxyglucose (FdG). FDG has been used to detect and test cancer for more than 10 years. It is superior to other existing contrast agents in contrast imaging of colorectal cancer, lung cancer 'melanoma' lymphoma and breast cancer. FDG has been used for metabolic angiographic pET scans of cancer, heart disease and neuropathy. It has now been found that diseases are treated by administering radiolabeled positron emitting compounds at significantly higher doses than those used for diagnostic and angiographic purposes. The present invention provides methods for treating diseases using positron-emitting compounds. The present invention is exhaustive. The present invention provides a novel method for treating a patient's disease, disease 'special cancer and related diseases. In specific embodiments, the present invention provides a method for treating a patient's disease comprising administering to the patient a therapeutically effective amount of a positron-emitting compound. The positron-emitting compound may contain one or more fluorine · 18, carbon · u, nitrogen · 13, or oxygen · 15 atoms. In another embodiment, the positron-emitting compound contains one or more oxygen-18 atoms. In a specific embodiment, the positron-emitting compound is cardiac fluorodeoxyglucose. In another specific embodiment, the gas deoxyglucose is 8f_2 • gas-2-deoxyglucose. In another embodiment, the positron is emitted and combined.
物為F-氣膽驗。於又一呈體眚祐你丨由 L /、體貫轭例中,此正子發射化合 物為[甲基-nC]膽鹼。 於一具體實施例中 此正子發射化合物給予病人的劑量The object is F-pneumobiliary test. In another example, you are shown in the example by L /, the penetrating yoke, the positron-emitting compound is [methyl-nC] choline. In a specific embodiment, the dose of this positron-emitting compound to a patient
1231215 五、發明説明(3 一具體實施例中 一具體貫施例中 一具體實施例中 一具體實施例中 一具體實施例中 一具體貫施例中 疋至^約用作診斷目的的1 ·5至2倍。於又一具體實施例中 此正子發射化合物的給予劑量是病人能耐受的最大劑量 。於又一具體實施例中,此正子發射化合物的給予劑量是 約30至1〇〇毫居里/5〇公斤體重。於又一具體實施例中,此正 子發射化合物的給予劑量是約30亳居里/50公斤體重。於又 一具體實施例中,此劑量是約40毫居里/50公斤體重。於又 此劑量是約50亳居里/50公斤體重。於又 此劑量是約60毫居里/50公斤體重。於又 此劑量是約70毫居里/50公斤體重。於又 此劑量是約80亳居里/50公斤體重。於又 此劑量是約90毫居里/50公斤體重。於又 此劑量是約100毫居里/50公斤體重。於 :-具體實施例中,以上述劑量給予的正子發射化合物是 F-氟去氧葡萄糖。於又—具體實施例中,以上述劑量給 予的正子發射化合物是,2ϋ去氧葡萄糖。 於另-具體實施例中,正子發射化合物可與任何免疫治 療,外科,放射治療,或其他化學治療一起於治療的任何 階段給予病人。 於又:具體實施例中’正子發射化合物是靜脈内給予。 於上述任一方法中,正子發射化合物可—天給予一或二 個劑置’給予二至+夭,彳鱼鋒仏名斗、IT - 、 十天連續給予或隔二星期至三星期作 非連-Η ,Ό 》另—具體實施例中,於上述任一方法中, 正子發射化合物可—天給予一或二個劑量,給予五 丄連續給予或隔二星期至三星期作非連續給予。於本發明 -具體實施例巾,給予五至=個劑量,每天給予。於本發 本紙張尺度適財_料_ x 297公爱厂 五、發明説明( 4 ) 明另-具體實施例中,不連續地給予五 二星期至=S如 ~ ^ 。於本發明另一具體實施例中,不連續地 給予五至十個劑量,費時二星期_。 、 於本發明一具體實施例中,治療的病是癌。於本發明另 一具體實施例中,此病是骨癌。 :又-具體實施例中,本發明包括_組合物,其含此處 乂化合物的劑量至少高於診斷用劑量的1 · 5至2倍。本發 括3有此處所述任-化合物的藥物作為治療癌症藥 ㈣:途。本發明也包括此等化合物的用於治療癌症的劑 里的單位劑量製劑供用於癌症的治療。 本發明詳诚 定義 "治療"疾病或病理學的意義是防止、排除'滅少其嚴重 性、緩和、或防止疾病或病理的進一步發展或擴大,或是 防止、排除、減少其嚴重性' 緩和、或防止疾病症狀或病 理情況的進-步發展或擴A。”治療"病主,個人,或病人 的定義是治療影響病主,個人,或病人的疾病。 化合物的"治療有效量"是足以防止、排除、減少其嚴重 性、緩和、或防止疾病或病理的進一步發展或擴大,或是 防止.、排除、減少其嚴重性、緩和、或防止疾病症狀或病 理情況的進一步發展或擴大的劑量。 "個人"或"病主"的意思是脊椎動物,較佳是哺乳動物, 更佳是人。"病人"是指進行過、正進行、或將要進行治療 的個人或病主。 本紙張尺度適用中S时標準(CNS) A4規格(21〇Χ297公爱) 1231215 A7 ___B7 五、發明説明(~~) '~ ^一 給予的意思是引入化合物至病主内。化合物的較佳給 予途徑是經靜脈給予。但也可用任何給予途徑,如經口, 局部’皮下,腹腔下,動脈内,吸入,經陰道,經直腸, 經鼻’引入腦脊趙液内,或點滴入身體各部。 本發明方法 本發明係關於正子發射放射醫藥品,如含氟·丨8的化合物 ’在人類疾病上的新穎治療用途。本發明方法特別有用於 治療癌及有關疾病。 可用於本發明的化合物是加進發射正子的放射性同位素 的化合物。發射正子的放射性同位素包括,但不限於,氟_ 18(半衰期11〇分鐘),碳-ΐι(半衰期2〇分鐘),氮-13(半衰期 10分鐘)’及氧-15(半衰期2分鐘)。可加入發射正子的放射 性同位素的化合物包括,但不限於,蛋白質,如單克隆及 多克隆抗及酶;線性’環形,及分支的肽,包括甲基化 的肽及加有D-胺基酸或非天然胺基酸的肽;擬肽 (peptidomimetics),如類肽(peptoids),肽核酸,以及其肽鍵 已還原的或不水解的肽;胺基酸,包括基因編碼的二十個 胺基酸,及其他天然的或非天然的胺基酸(包括,但不限於 ’肽核酸,D-胺基酸,胺基酸醇,乙酿化胺基酸,其他醯 化的胺基酸,胺基酸酯,胺基酸醯胺,β_胺基酸,肽核酸 等);核酸,包括,但不限於,DNA,RNA,核苔酸,核苔 ’核脊酸類似物及核苔類似物;碳水化合物,包括,作不 限於,葡萄糖,去氧葡萄糖,氟去氧葡萄糖,2 -氟_ 2 •去 氧葡萄糖,水果糖,蔗糖,半乳糖,乳糖,等等;藥物, -8 - 本紙張尺度適用中@ Η家標準(CNS) Α4規格(21GX 297公釐) ' -—--- 1231215 五、發明説明(6 A7 B71231215 V. Description of the invention (3 A specific embodiment in a specific embodiment A specific embodiment in a specific embodiment A specific embodiment in a specific embodiment In a specific embodiment in the specific examples are used for diagnostic purposes 1 · 5 to 2 times. In another embodiment, the dose of the positron-emitting compound is the maximum dose that the patient can tolerate. In yet another embodiment, the dose of the positron-emitting compound is about 30 to 100. Millicuries / 50 kg body weight. In yet another embodiment, the dose of the positron-emitting compound is about 30 亳 Curie / 50 kg body weight. In yet another embodiment, the dose is about 40 millicubes. Li / 50 kg body weight. This dose is about 50 亳 Curie / 50 kg body weight. This dose is about 60 mCi / 50 kg body weight. This dose is about 70 mCi / 50 kg body weight. .This dosage is about 80 亳 Curie / 50 kg body weight. This dosage is about 90 milliCurie / 50 kg body weight. This dosage is about 100 milliCurie / 50 kg body weight. Yu: -Specific In the embodiment, the positron-emitting compound administered at the above-mentioned dose is F-fluorine Oxyglucose. In another embodiment, the positron emitting compound administered at the above dose is 2ϋ deoxyglucose. In another embodiment, the positron emitting compound can be used with any immunotherapy, surgery, radiation therapy, or other Chemotherapy is given to the patient at any stage of the treatment. Yu You: In the specific embodiment, the 'positron-emitting compound is administered intravenously. In any of the above methods, the positron-emitting compound can be administered in one or two doses per day.' Up to + 夭, 彳 鱼 仏 仏 名 斗, IT-, continuous administration for ten days or non-continuous -Η, Ό every two to three weeks ”In addition, in specific embodiments, in any of the above methods, positron emission compounds One to two doses can be given every day, five to five consecutive doses or non-continuous administration every two to three weeks. In the present invention-specific embodiment, five to five doses are given daily. Paper size suitable for money_ 料 _ x 297 Gongai Factory V. Description of the invention (4) In addition-in specific embodiments, discontinuously given for five or two weeks to = S 如 ~ ^. In another specific embodiment of the present invention In the embodiment, five to ten doses are administered discontinuously, which takes two weeks. In one embodiment of the present invention, the disease to be treated is cancer. In another embodiment of the present invention, the disease is bone cancer. : Also-in a specific embodiment, the present invention includes a composition containing a hydrazone compound at a dose of at least 1.5 to 2 times higher than a diagnostic dose. This disclosure includes any of the compounds described herein. The drug is used as a drug for cancer treatment: the invention. The present invention also includes unit dose preparations of these compounds for the treatment of cancer for the treatment of cancer. The present invention defines " treatment " The significance is to prevent, eliminate, or reduce the severity of the disease, alleviate, or prevent the further development or expansion of the disease or pathology, or prevent, eliminate, reduce the severity of the disease, alleviate, or prevent the further development of disease symptoms or pathological conditions Or expand A. "Treatment" is defined as the treatment of a disease that affects the patient, individual, or patient. A "therapeutic effective amount" of a compound is sufficient to prevent, exclude, reduce its severity, alleviate, or prevent Dose for further development or expansion of disease or pathology, or to prevent, exclude, reduce its severity, alleviate, or prevent further development or expansion of disease symptoms or pathological conditions. &Quot; Individual " or " patient " Means vertebrate, preferably mammal, more preferably human. &Quot; Patient " refers to an individual or patient who has undergone, is undergoing, or is about to undergo treatment. This paper standard applies to the S time standard (CNS) ) A4 specification (21〇 × 297 public love) 1231215 A7 ___B7 V. Description of the invention (~~) '~ ^ One means to introduce the compound into the subject. The preferred route of administration of the compound is intravenous administration. But it can also be used Any route of administration, such as oral, topical 'subcutaneous, subperitoneal, intraarterial, inhalation, transvaginal, transrectal, nasal' is introduced into the cerebrospinal fluid, or dripped into various parts of the body. Method The present invention relates to positron-emitting radiopharmaceuticals, such as the novel therapeutic use of compounds containing fluorine · 8 in human diseases. The method of the present invention is particularly useful for treating cancer and related diseases. Compounds that can be used in the present invention are added to A positron-emitting radioisotope compound. A positron-emitting radioisotope includes, but is not limited to, fluorine-18 (half-life 10 minutes), carbon-carbon (half-life 20 minutes), nitrogen-13 (half-life 10 minutes), and oxygen. -15 (half-life 2 minutes). Compounds to which positron-emitting radioisotopes can be added include, but are not limited to, proteins such as monoclonal and polyclonal antibodies and enzymes; linear 'circular', and branched peptides, including methylated peptides And peptides with D-amino acids or unnatural amino acids; peptidomimetics, such as peptoids, peptide nucleic acids, and peptides whose peptide bonds have been reduced or not hydrolyzed; amino acids, Including twenty amino acids encoded by genes, and other natural or non-natural amino acids (including, but not limited to, 'peptide nucleic acids, D-amino acids, amino alcohols, ethyl alcohols, its Tritiated amino acids, amino esters, amino acids, β-amino acids, peptide nucleic acids, etc.); nucleic acids, including, but not limited to, DNA, RNA, nuclear acid, nuclear moss' nuclear spine Acid analogs and nuclear moss analogs; carbohydrates including, but not limited to, glucose, deoxyglucose, fluorodeoxyglucose, 2-fluoro-2 • deoxyglucose, fruit sugar, sucrose, galactose, lactose, etc. Drugs, -8-Applicable to this paper size @ Η 家 标准 (CNS) Α4 size (21GX 297 mm) '--------- 1231215 V. Description of the invention (6 A7 B7
如化學治療劑·Λ小有機分子,較佳是其分子量小於1〇〇〇, 更佳是其分子量小於600,包括,但不限於,膽驗,I膽驗 ’及乙醯膽·鹼;及見於病主:生化反應的基質。 可用於本發明的化合物是氟去氧葡萄糖(稱作氟_ 18FDG , 18F-FDG ,還簡單稱作FDG)。一般而言,是用18ρ_ 2 -氟-2-去氧葡萄糖。(此化合物的合成以公佈,也是精於 此技藝者已知的。)FDG較佳是經靜脈内注射給予病主。 FDG經靜脈内給予後,大部分放射醫藥品迅即由循環清除 ’其半衰期少#1分鐘,散佈於大空間内,但也有些部位 的半衰期達1.5小時之久。此物質主由惡性腫瘤組織,感染 組織,心肌,及腦吸收。以狗(7)作研究顯示其他器官也有 相當濃度,特別是脾,肝,及腎,但於人作的研究則不見 此等器官有明顯吸收(9)。用於本發明的其他化合物包括氣· 18氟膽鹼及[nC曱基]膽鹼。 用於本發明方法的FDG的治療劑量至少是3〇毫居里/ 5〇公 斤體重/劑。治療劑量一般是30至100毫居里/5〇公斤體重。 所以其他可用的劑量是30,40,50,60 , 70,80,90,及1〇〇毫 居里/50公斤體重/劑。 約20%給予的氟-18是於第一個2小時内由尿排出(8)。由 Jones et al (8)所得平均尿的術數據可以引導出,身體内滯留 的總FDG量,就劑量學目的言,可以12分鐘半時(〇 〇75),i 5 小時半時(0.225) ’及無限(〇.70)的多指數函數表示。心肌及 腦於8分鐘吸收半時間分別吸收〇 〇4及〇 〇6部分,其健留時 與氟-18的半衰期相比是長的。於全身内的殘餘活性設定是 -9-Such as chemotherapeutic agents. Λ small organic molecules, preferably having a molecular weight of less than 1,000, and more preferably having a molecular weight of less than 600, including, but not limited to, biliary test, biliary test and acetylcholine; and Found in patients: the substrate of biochemical reactions. A compound that can be used in the present invention is fluorodeoxyglucose (referred to as fluorine-18FDG, 18F-FDG, also simply referred to as FDG). In general, 18ρ 2 -fluoro-2-deoxyglucose is used. (The synthesis of this compound is published and known to those skilled in the art.) FDG is preferably administered to a patient via intravenous injection. After intravenous administration of FDG, most radiopharmaceuticals are quickly cleared by circulation. Its half-life is less than 1 minute and is scattered in large spaces, but the half-life of some parts is as long as 1.5 hours. This substance is mainly absorbed by malignant tumor tissues, infected tissues, myocardium, and brain. Studies in dogs (7) have shown that other organs also have considerable concentrations, especially the spleen, liver, and kidney, but studies in humans have not shown that these organs have significant absorption (9). Other compounds useful in the present invention include qi 18fluorocholine and [nCfluorenyl] choline. The therapeutic dose of FDG used in the method of the present invention is at least 30 millicuries / 50 kg body weight / dose. The therapeutic dose is generally 30 to 100 millicuries / 50 kg body weight. So other available doses are 30, 40, 50, 60, 70, 80, 90, and 100 milliCurie / 50 kg body weight / dose. About 20% of the administered F-18 is excreted in the urine within the first 2 hours (8). The average urinary data obtained by Jones et al (8) can be used to guide the total amount of FDG retained in the body. For dosimetry purposes, it can be 12 minutes and a half hours (〇75) and 5 hours and a half hours (0.225). 'And infinite (0.70) multi-exponential function representation. The myocardium and the brain absorb the 004 and 006 parts at 8 minutes and a half time, respectively, and their retention time is longer than the half-life of fluorine-18. The residual activity setting throughout the body is -9-
裝 訂Binding
線 1231215 A7 ____B7 五、發明説明(7 ) 均勻分佈於所有組織而非僅只腦和心臟。根據腎膀脱模型 顯不,0.3部分是在12分鐘㈧义丨及丨5小時(〇 75)半時内由腎 系統排出。 由此生物動力學推演,以1〇亳居里氟_18FDG劑量ρΕτ掃 描估計出的正常組織劑量當量(EDE)為約i雷姆(rem)。用於 惡性腫瘤時,設定腫瘤直徑為i公分,用相同劑量1〇亳居 里’則EDE應為137.5雷姆,吸收率1%,達55〇1雷姆時腫瘤 的,收率為4%⑹。-般而言,腫瘤的大小及吸收百分比 決定了惡性腫瘤組織吸收的確實劑量。 以此计算,30毫居里的FDG劑量,此已為用於診斷目的 1〇毫居里劑量的三倍,吸收率為4%的1公分腫瘤將接受 1,650雷姆的EDE ^此3〇毫居里劑量的FD(}可每天給予一或二 次,連續五至十天(可每天使用或隔一段時間非連續使用) ,EDE會作對應的累積。累積的EDE可藉適宜地修改劑量作 调整。此計算是設定FDG低吸受不因腫瘤退縮或其他因素 而以所4貝失。 對於重要器官如腦及心臟的毒性,因此等器官與腫瘤相 比幸乂大,所以相對較低。對心肌而言,以%毫居里作5 次療程後,其正常EDE2.2雷姆會增至33雷姆。是以,可估 計到一個療程的此種治療對腦及心肌的損傷是極小的。如 果病人的這些器官以前曾接受過放射治療,應小心適度調 整劑量,以防有重大損傷。根據普遍使用的國際安全標準 放射工作者每年單一器官的劑量限制是5〇雷姆⑷。但如 以治療為目的,此數字可放寬。 -10-Line 1231215 A7 ____B7 V. Description of the Invention (7) It is evenly distributed in all tissues, not just the brain and heart. According to the renal detachment model, the 0.3 part was excreted by the renal system within 12 minutes and 5 hours (0 75). From this biodynamic deduction, the normal tissue dose equivalent (EDE) estimated from a 10 亳 Curie fluoride-18FDG dose ρEτ scan is approximately i Rem. For malignant tumors, set the diameter of the tumor to i cm and use the same dose of 10 亳 Curie '. The EDE should be 137.5 Rem and the absorption rate is 1%. When the tumor reaches 5501 Rem, the yield is 4%. Alas. -In general, tumor size and percentage absorption determine the exact dose absorbed by the malignant tumor tissue. Based on this calculation, an FDG dose of 30 mCi, which is three times the 10 mCi dose for diagnostic purposes, and a 1 cm tumor with an absorption rate of 4% will receive an EDE of 1,650 Rem ^ This 3 The dose of FD () of 〇 Curie can be given once or twice a day for five to ten consecutive days (can be used every day or intermittently at intervals), and the EDE will be accumulated accordingly. The accumulated EDE can be modified as appropriate. The dose is adjusted. The calculation is to set the FDG hypoabsorption not to be lost due to tumor shrinkage or other factors. For important organs such as brain and heart toxicity, so other organs are relatively large compared with tumors, so they are relatively Low. For myocardium, the normal EDE2.2 Rem will increase to 33 Rem after 5 treatments with% mCurie. Therefore, it can be estimated that one treatment course will damage the brain and myocardium. It is extremely small. If these organs of the patient have previously received radiation therapy, care should be taken to moderately adjust the dose to prevent major injuries. According to the commonly used international safety standards, the annual dose limit for a single organ for radiation workers is 50 Rem⑷ ... but for therapeutic purposes This number can be relaxed. -10-
五 發明説明( 8 ) 對腦的毒性還可藉使用其他的氣_18標記的化合物,如氣 :::二CH) ’而進—步降低。FCH不像FDG-樣容易累積 《正吊月由組織内,泛右尤 , 且有在腫瘤組織内達到高濃度的優點(j ’ 2β’、3 ’ 5)。本發明方法也可使用[甲基-丨1C]膽鹼。. 疋以本發明提供將治療劑直接投送至惡性組織的方法, 對惡性組織構成損害而對健康組織的損害極小。本發明方 t可單獨使用或與傳統的癌治療方法結合使用,如與放射 :療’化學治#,免疫治療及外科治療結合使用。是以, 發明提供治療癌及其他疾病的有用的方法。 f例i 個案病歷 以六個月。他曾 作過腎切除,給 以MRI顯示左側 六十六歲老年男性’自訴左侧髖關節痛 有腎細胞癌病史,兩年以前侵入腎靜脈。 予干擾素治療六個月。現在發病期中, 腸骨處有一孤立轉移’直徑約7公分。 以氟-18 FDG治療 經注 主觀 。六 "τ' , 1日間三至 射給予後未見有副作用。於六週結束時,病灶大 症狀都明顯減低。此時給病人以確定的外部放射 個月後,病人已無症狀,骨盆病灶已痊療。, PE丁掃描結果 每一次治療後及每一 降低。 於FDG治療前及治療中都作過pET。 次外部放射治療後都顯示標準吸收值 結論 -11 - 本紙張尺度it 中國國家標準(CNS) A4規格(210X297^ 1231215 A7V. Explanation of the invention (8) The toxicity to the brain can be further reduced by using other qi_18 labeled compounds, such as qi ::: diCH) '. FCH is not as easy to accumulate as FDG. "The hanging moon is in the tissue, especially pan right, and it has the advantage of reaching high concentrations in tumor tissue (j '2β', 3 '5). The method of the present invention can also use [methyl- 1C] choline. (1) The present invention provides a method for directly delivering a therapeutic agent to malignant tissue, which causes damage to malignant tissue and minimal damage to healthy tissue. The method of the present invention can be used alone or in combination with traditional cancer treatment methods, such as combined with radiation: treatment 'chemical treatment, immunotherapy and surgical treatment. Therefore, the invention provides a useful method for treating cancer and other diseases. Case f of case i is six months. He had had a nephrectomy and showed an MRI on the left. A 66-year-old man on the left reported that he had pain in the left hip joint with a history of renal cell carcinoma. He had invaded the renal vein two years ago. Interferon was given for six months. During the onset of the disease, there is an isolated metastasis at the intestine bone about 7 cm in diameter. Treatment with fluorine-18 FDG was subjective by injection. Six " τ ', no side effects were seen after 3 to 3 days of administration. At the end of six weeks, the major symptoms of the lesions were significantly reduced. At this time, the patient was given ascertained external radiation for months. The patient was asymptomatic and the pelvic lesions had been cured. PE scan results after each treatment and each decrease. PET was performed before and during FDG treatment. Standard absorption values were shown after each external radiation treatment. Conclusion -11-This paper size it Chinese National Standard (CNS) A4 specification (210X297 ^ 1231215 A7
五、發明説明(9 ) 治療二次後,由於自腎癌轉移來的孤立的骨盆内的癌累 積的氟-18 FDG的正子發射產生”放射,已得到肯定的反應 。由腎細胞癌二次轉移產生的骨癌則難以治療,此病基本 上對化學治療現已流行的免疫治療有抗性。藉了以氟-18 FDG所得的正面反應,及繼之而作的外部束放射冶療,相 信次病人會在存活期内有良好的生活品質,長時期病情不 會在有發展,也無症狀。以此案例的病史而言,此一結果 是以其他治療難以達成的。 春者文獻 1. Roivainen A. et al., uBlood metabolism of [methyl-1 lC]choline; implications for in vivo imaging with positron emission tomography,” Eur. J.V. Description of the invention (9) After the second treatment, the radiation produced by the positron emission of fluorine-18 FDG accumulated from isolated pelvic cancer metastasized from renal cancer has received a positive response. Secondary to renal cell carcinoma Metastatic bone cancer is difficult to treat, and the disease is basically resistant to immunotherapy that is now popular with chemotherapy. By virtue of the positive response obtained with fluorine-18 FDG and subsequent external beam radiation therapy, It is believed that the secondary patient will have a good quality of life during the survival period, and the long-term condition will not develop and be asymptomatic. In the case of the medical history, this result is difficult to achieve with other treatments. Chunzhe Literature 1 Roivainen A. et al., UBlood metabolism of [methyl-1 lC] choline; implications for in vivo imaging with positron emission tomography, "Eur. J.
Nucl. Med. 27(1):25-32 (Jan 2000). 2. Kobori 0. et al·,“Positron emission tomography of esophageal carcinoma using nC-choline and I8F-fluorodeoxyglucose: a novel method of preoperative lymph node staging,Cancer 86(9):1638-48 (Nov 1 1999). 3· Hara T. et al” “PET imaging of brain tumor with [methyl-1 々choline,”Nucl. Med. 27 (1): 25-32 (Jan 2000). 2. Kobori 0. et al ·, "Positron emission tomography of esophageal carcinoma using nC-choline and I8F-fluorodeoxyglucose: a novel method of preoperative lymph node staging , Cancer 86 (9): 1638-48 (Nov 1 1999). 3. · Hara T. et al "" PET imaging of brain tumor with [methyl-1 々choline, "
The Journal of Nuclear Medicine, 38(6):842-7 (June 1997). 4. Laws of the Hong Kong Government: Radiation (Control of Irradiating Apparatus), Regulations on, (Cap. 303, Section 13) (October 1, 1965), L.N. 114 of 1965· 5. Coleman R.E. et al·,“Preliminary Evaluation of F-l 8 Fluorcholine (FCH) as a PET Tumor Imaging Agent,” Scientific Paper from 12th Annual International PET Conference, October 15-18, 2000, Washington, D.C. -12- ^纸張尺度適用中國國家標準(CNS) A4規格(210X297公釐) 1231215 A7 B7 五、發明説明(1〇 ) 6. Calculation by Vanessa Gates, MS, and C. Oliver Wong, MBBS, PhD, MD, FACP, FACNP, Ohio State University and Michigan State University. 7. Gallagher, B.M. et al., ^Radiopharmaceuticals XXVII: 18F-labelled 2-deoxy-2-fluoro-D-glucose as a radiopharmaceutical for measuring myocardial glucose metabolism in vivo. Tissue distribution and imaging studies in animals,” J. Nucl. Med. 18:990-996 (1977). 8. Jones S.C. et al., uThe radiation dosimetry of 2-F-18 fluoro-2-deoxy-D-glucose in man;1 J. Nucl. Med. 23:613-617 (1982). 9. Phelps, M.E· et al.,“Investigation of [18F] 2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism,J. Nucl. Med. 19:1311-1319 (1978). 10. Gopal B. Saha et al., ''Cyclotrons and Positron Emission Tomography Radiopharmaceuticals for Clinical Imaging,” Seminars in Nuclear Medicine, Vol. XXII, No. 3 (July 1992), pp. 150-161. 所有專利,專利申請,及其他此處述及的出版物今一併 全文附上供參考。 雖則為了清楚及易於了解起見,本發明已藉了說明及實 例作了詳述,精於此技藝者當會清楚理解作一定的變化及 修改可能是務實的。所以,前述說明及實例不能理解為對 本發明範圍的限制,本發明範圍是如申請專利範圍所描述 者0 -13- 本纸張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐)The Journal of Nuclear Medicine, 38 (6): 842-7 (June 1997). 4. Laws of the Hong Kong Government: Radiation (Control of Irradiating Apparatus), Regulations on, (Cap. 303, Section 13) (October 1 , 1965), LN 114 of 1965 5. Coleman RE et al ·, "Preliminary Evaluation of Fl 8 Fluorcholine (FCH) as a PET Tumor Imaging Agent," Scientific Paper from 12th Annual International PET Conference, October 15-18, 2000 , Washington, DC -12- ^ Paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 1231215 A7 B7 V. Description of invention (1〇) 6. Calculation by Vanessa Gates, MS, and C. Oliver Wong , MBBS, PhD, MD, FACP, FACNP, Ohio State University and Michigan State University. 7. Gallagher, BM et al., ^ Radiopharmaceuticals XXVII: 18F-labelled 2-deoxy-2-fluoro-D-glucose as a radiopharmaceutical for measuring myocardial glucose metabolism in vivo. Tissue distribution and imaging studies in animals, "J. Nucl. Med. 18: 990-996 (1977). 8. Jones SC et al., uThe radiation dosimetry of 2-F -18 fluoro-2-deoxy-D-glucose in man; 1 J. Nucl. Med. 23: 613-617 (1982). 9. Phelps, ME · et al., "Investigation of [18F] 2-fluoro- 2-deoxyglucose for the measure of myocardial glucose metabolism, J. Nucl. Med. 19: 1311-1319 (1978). 10. Gopal B. Saha et al., `` Cyclotrons and Positron Emission Tomography Radiopharmaceuticals for Clinical Imaging, '' Seminars in Nuclear Medicine, Vol. XXII, No. 3 (July 1992), pp. 150-161. All patents, patent applications, and other publications mentioned herein are hereby incorporated by reference in their entirety. Although for the sake of clarity and ease of understanding, the present invention has been described in detail through descriptions and examples, those skilled in the art will clearly understand that certain changes and modifications may be pragmatic. Therefore, the foregoing descriptions and examples cannot be understood as limiting the scope of the present invention. The scope of the present invention is as described in the scope of the patent application. 0-13
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