正电子发射断层显像剂2-脱氧-2-[¹⁸F]氟-D-葡萄糖在乳腺癌中具有治疗潜力。

Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer.

作者信息

Moadel Renee M, Nguyen Andrew V, Lin Elaine Y, Lu Ping, Mani Joseph, Blaufox M Donald, Pollard Jeffrey W, Dadachova Ekaterina

机构信息

Department of Nuclear Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA.

出版信息

Breast Cancer Res. 2003;5(6):R199-205. doi: 10.1186/bcr643. Epub 2003 Aug 22.

DOI:10.1186/bcr643

PMID:14580255

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC314404/

Abstract

BACKGROUND

Novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer.

METHODS

Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic mice with tumors 0.5-1 cm in diameter were imaged with 18F-FDG, and tumor to liver ratios (TLRs) were calculated. The radiotoxicity of 18F-FDG administration was determined in healthy mice. PyMT mice with small (0.15-0.17 cm) and large (more than 1 cm) tumors were treated with 2-4 mCi of 18F-FDG, and control C3H/B6 mice with 3 mCi of 18F-FDG. At 10 days after treatment the tumors and control mammary glands were analyzed for the presence of apoptotic and necrotic cells. Five patients with breast cancer and metastatic disease were evaluated and standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the doses to the tumor were calculated.

RESULTS

Doses up to 5 mCi proved to be non-radiotoxic to normal organs. The 18F-FDG uptake in mouse tumors showed an average TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small tumors. Cell death through the necrotic pathway was seen in large tumors, and was accompanied by tumor fragmentation and infiltration with leukocytes. Normal mammary tissues were not damaged. A human 18F-FDG dose delivering 200 rad to the red marrow (less than 5% damage) was calculated to be 4.76 Ci for a 70 kg woman, and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs of 1, 5 and 10, respectively.

CONCLUSION

We have shown that positrons delivered by 18F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study of breast cancer patients suggests that the tumor and normal organ dosimetry of 18F-FDG makes it suitable for therapy of this malignancy.

摘要

背景

对于标准治疗无效的乳腺癌患者，需要新的治疗方法。在乳腺癌动物模型以及回顾性地在转移性乳腺癌患者中，对2-脱氧-2-[18F]氟-D-葡萄糖（18F-FDG）作为一种潜在的放射分子治疗剂进行了评估。

方法

对直径为0.5 - 1厘米肿瘤的多瘤病毒中间T抗原（PyMT）和小鼠乳腺肿瘤病毒-NeuT转基因小鼠进行18F-FDG成像，并计算肿瘤与肝脏比值（TLR）。在健康小鼠中确定给予18F-FDG的放射毒性。对肿瘤小（0.15 - 0.17厘米）和大（超过1厘米）的PyMT小鼠给予2 - 4毫居里的18F-FDG进行治疗，对对照C3H/B6小鼠给予3毫居里的18F-FDG。治疗后10天，分析肿瘤和对照乳腺组织中凋亡和坏死细胞的存在情况。对5例患有乳腺癌和转移性疾病的患者进行评估，并计算肿瘤的标准化摄取值（SUV）、最大耐受剂量以及肿瘤所接受的剂量。

结果

高达5毫居里的剂量被证明对正常器官无放射毒性。小鼠肿瘤中18F-FDG的摄取显示平均TLR为1.6。对小鼠的治疗导致小肿瘤中出现凋亡性细胞死亡。在大肿瘤中可见通过坏死途径的细胞死亡，并伴有肿瘤碎片化和白细胞浸润。正常乳腺组织未受损。对于一名70千克的女性，计算得出向红骨髓输送200拉德（损伤小于5%）的人体18F-FDG剂量为4.76居里，对于SUV分别为1、5和10的情况，肿瘤所接受的剂量分别计算为220、1100和2200拉德。