Harrington K J, Mohammadtaghi S, Uster P S, Glass D, Peters A M, Vile R G, Stewart J S
Oncology Unit, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, United Kingdom.
Clin Cancer Res. 2001 Feb;7(2):243-54.
The biodistribution and pharmacokinetics of (111)In-DTPA-labeled pegylated liposomes (IDLPL) were studied in 17 patients with locally advanced cancers. The patients received 65-107 MBq of IDLPL, and nuclear medicine whole body gamma camera imaging was used to study liposome biodistribution. The t(1/2beta) of IDLPL was 76.1 h. Positive tumor images were obtained in 15 of 17 studies (4 of 5 breast, 5 of 5 head and neck, 3 of 4 bronchus, 2 of 2 glioma, and 1 of 1 cervix cancer). The levels of tumor liposome uptake estimated from regions of interest on gamma camera images were approximately 0.5-3.5% of the injected dose at 72 h. The greatest levels of uptake were seen in the patients with head and neck cancers [33.0 +/- 15.8% ID/kg (percentage of injected dose/kg)]. The uptake in the lung tumors was at an intermediate level (18.3 +/- 5.7% ID/kg), and the breast cancers showed relatively low levels of uptake (5.3 +/- 2.6% ID/kg). These liposome uptake values mirrored the estimated tumor volumes of the various tumor types (36.2 +/- 18.0 cm3 for squamous cell cancer of the head and neck, 114.5 +/- 42.0 cm3 for lung tumors, and 234.7 +/- 101.4 cm3 for breast tumors). In addition, significant localization of the liposomes was seen in the tissues of the reticuloendothelial system (liver, spleen, and bone marrow). One patient with extensive mucocutaneous AIDS-related Kaposi sarcoma was also studied according to a modified protocol, and prominent deposition of the radiolabeled liposomes was demonstrated in these lesions. An additional two patients with resectable head and neck cancer received 26 MBq of IDLPL 48 h before undergoing surgical excision of their tumors. Samples of the tumor, adjacent normal mucosa, muscle, fat, skin, and salivary tissue were obtained at operation. The levels of tumor uptake were 8.8 and 15.9% ID/kg, respectively, with tumor uptake exceeding that in normal mucosa by a mean ratio of 2.3:1, in skin by 3.6:1, in salivary gland by 5.6:1, in muscle by 8.3:1, and in fat by 10.8:1. These data strongly support the development of pegylated liposomal agents for the treatment of solid tumors, particularly those of the head and neck.
在17例局部晚期癌症患者中研究了铟-111标记的聚乙二醇化脂质体（IDLPL）的生物分布和药代动力学。患者接受65 - 107 MBq的IDLPL，并使用核医学全身γ相机成像研究脂质体的生物分布。IDLPL的t(1/2β)为76.1小时。17项研究中的15项获得了阳性肿瘤图像（5例乳腺癌中的4例、5例头颈癌中的5例、4例支气管癌中的3例、2例神经胶质瘤中的2例以及1例宫颈癌）。根据γ相机图像上感兴趣区域估计，72小时时肿瘤脂质体摄取水平约为注射剂量的0.5 - 3.5%。摄取水平最高的是头颈癌患者[33.0±15.8% ID/kg（注射剂量/千克的百分比）]。肺肿瘤的摄取处于中等水平（18.3±5.7% ID/kg），乳腺癌的摄取水平相对较低（5.3±2.6% ID/kg）。这些脂质体摄取值反映了各种肿瘤类型的估计肿瘤体积（头颈鳞状细胞癌为36.2±18.0 cm³，肺肿瘤为114.5±42.0 cm³，乳腺癌为234.7±101.4 cm³）。此外，在网状内皮系统（肝脏、脾脏和骨髓）组织中可见脂质体的显著定位。还根据改良方案对1例患有广泛黏膜皮肤型艾滋病相关卡波西肉瘤患者进行了研究，在这些病变中显示出放射性标记脂质体的显著沉积。另外2例可切除的头颈癌患者在肿瘤手术切除前48小时接受了26 MBq的IDLPL。手术时获取了肿瘤、相邻正常黏膜、肌肉、脂肪、皮肤和唾液组织的样本。肿瘤摄取水平分别为8.8% ID/kg和15.9% ID/kg，肿瘤摄取超过正常黏膜的平均比例为2.3:1，超过皮肤的比例为3.6:1，超过唾液腺的比例为5.6:1，超过肌肉的比例为8.3:1，超过脂肪的比例为10.8:1。这些数据有力地支持了开发聚乙二醇化脂质体药物用于治疗实体瘤，特别是头颈实体瘤。
