Lin W Y, Lin C P, Yeh S J, Hsieh B T, Tsai Z T, Ting G, Yen T C, Wang S J, Knapp F F, Stabin M G
Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Eur J Nucl Med. 1997 Jun;24(6):590-5. doi: 10.1007/BF00841394.
The search for an ideal radioisotope for systemic radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays and having a short physical half-life of 16.9 h, rhenium-188 is a very good potential candidate for systemic radiotherapy. In this study, we labeled hydroxyethylidene diphosphonate (HEDP) with 188Re and analyzed the biodistribution and bone uptake following intravenous injection in rats to assess its potential for clinical use. The rats were injected with approximately 14.8 MBq (0.4 mCi) 188Re-HEDP in a volume of 0.1 ml intravenously and then sacrificed at 1 h, 24 h, or 48 h (four rats at each time). Samples (about 0.1 g) of lung, liver, kidney, spleen, testis, muscle, stool, and bone (thoracic vertebra) were taken and weighed carefully. In addition, a 1-ml sample of blood was drawn from the heart and 1 ml of urine was taken from the urinary bladder immediately after killing. Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (% ID/g or ml). Bone lesions were created in the right tibial bone in three rabbits to calculate the lesion to normal uptake ratio (L/N ratio). The biodistribution data showed that the radioactivity in the bone tissue was as high as 1.877% ID/g at 1 h and that it climbed to 2.017% ID/g at 4 h. The activity level in the kidney was highest at 1 h but declined rapidly throughout the study. The radioactivities in the lung, liver, muscle, spleen, testis, blood, and stool were all lower than 0.3% ID/g at 1 h and also declined rapidly. The biological half-life in bone was the longest (60.86 h). In contrast, the biological half-lives in muscle and blood were short (2.99 h and 6.21 h respectively). The concentrations of radioactivity in muscle, spleen, testis, and stool were quite low throughout the study. Most of the radiotracer was excreted by the urinary system. The L/N ratio was 4.23+/-0.21 in rabbits injected with 188Re-HEDP and 4.25+/-0.23 in those injected with technetium-99m methylene diphosphonate. In conclusion, we would suggest that 188Re-HEDP is a very good potential candidate for the treatment of bone metastases because of the following characteristics: (1) it is generator produced; (2) it has a short half-life; (3) it emits gamma rays suitable for imaging; (4) there is highly selective uptake in the skeletal system and bone lesions; and (5) it has a low non-target uptake and rapid clearance in nonosseous tissue.
对用于全身放疗的理想放射性同位素的探索仍在继续。铼-188作为一种由发生器产生的同时发射β射线和γ射线且物理半衰期较短（16.9小时）的放射性同位素，是全身放疗的一个非常有潜力的候选者。在本研究中，我们用188Re标记了羟基亚乙基二膦酸（HEDP），并在大鼠静脉注射后分析了其生物分布和骨摄取情况，以评估其临床应用潜力。给大鼠静脉注射约14.8 MBq（0.4 mCi）的188Re-HEDP，体积为0.1 ml，然后在1小时、24小时或48小时处死（每个时间点4只大鼠）。仔细采集并称重肺、肝、肾、脾、睾丸、肌肉、粪便和骨（胸椎）的样本（约0.1 g）。此外，处死大鼠后立即从心脏抽取1 ml血液样本，并从膀胱采集1 ml尿液。计算组织浓度并以每克或每毫升注射剂量的百分比（% ID/g或ml）表示。在3只兔子的右胫骨制造骨病变，以计算病变与正常摄取比值（L/N比值）。生物分布数据显示，骨组织中的放射性在1小时时高达1.877% ID/g，在4小时时升至2.017% ID/g。肾脏中的活性水平在1小时时最高，但在整个研究过程中迅速下降。肺、肝、肌肉、脾、睾丸、血液和粪便中的放射性在1小时时均低于0.3% ID/g，且也迅速下降。骨中的生物半衰期最长（60.86小时）。相比之下，肌肉和血液中的生物半衰期较短（分别为2.99小时和6.21小时）。在整个研究过程中，肌肉、脾、睾丸和粪便中的放射性浓度相当低。大部分放射性示踪剂通过泌尿系统排出。注射188Re-HEDP的兔子的L/N比值为4.23±0.21，注射锝-99m亚甲基二膦酸盐的兔子的L/N比值为4.25±0.23。总之，我们认为188Re-HEDP因其以下特性是治疗骨转移的一个非常有潜力 的候选者：（1）由发生器产生；（2）半衰期短；（3）发射适合成像的γ射线；（4）在骨骼系统和骨病变中有高度选择性摄取；（5）在非骨组织中的非靶摄取低且清除迅速。
