Hoh Carl K, Wallace Anne M, Vera David R
Department of Radiology, University of California San Diego, La Jolla, CA 92093, USA.
Nucl Med Biol. 2003 Jul;30(5):457-64. doi: 10.1016/s0969-8051(03)00028-3.
We report the preclinical testing of a synthetic receptor-binding macromolecule, [(99m)Tc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, K(D) = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [(99m)Tc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 +/- 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10(-2) mSv/MBq. This preclinical study demonstrates that [(99m)Tc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose.
我们报告了一种用于前哨淋巴结检测的合成受体结合大分子[（99m）Tc]二乙三胺五乙酸-甘露糖基葡聚糖（36 kDa，每个葡聚糖含8个二乙三胺五乙酸和55个甘露糖基单元，解离常数K（D）=0.12 nM）的临床前测试。非临床安全性研究包括心脏药理学安全性研究、在大鼠和兔子足垫给药后按人体剂量换算的50倍和500倍剂量下进行的急性毒理学和病理学研究，以及在兔子肌肉注射按人体剂量换算的100倍和1000倍剂量后的血管周围刺激研究。在兔子身上进行的15分钟、1小时和3小时的生物分布研究表明，[（99m）Tc]二乙三胺五乙酸-甘露糖基葡聚糖从后足垫清除的生物半衰期为2.21±0.27小时。除了兔子出现轻度肝细胞肥大外，未发现毒理学或病理学异常。静脉给药对生存率、任何临床观察、心电图或血压均无影响。肌肉注射对生存率、临床观察、注射部位观察或注射部位组织病理学均无影响。受影响乳房的估计吸收辐射剂量为0.15 mGy/MBq，有效剂量为1.06×10（-2）mSv/MBq。这项临床前研究表明，[（99m）Tc]二乙三胺五乙酸-甘露糖基葡聚糖没有毒性，具有可接受的生物分布和辐射剂量。
