Rhenium-188 hydroxyethylidene diphosphonate: A new generator-produced radiotherapeutic drug of potential value for the treatment of bone metastases
Rhenium-188 hydroxyethylidene diphosphonate: A new generator-produced radiotherapeutic drug of potential value for the treatment of bone metastases
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DOI：
10.1007/bf00841394
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发表时间：
1997-06-01
期刊：
影响因子：
--
通讯作者：
Stabin, MF
中科院分区：
文献类型：
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作者：
Lin, WY;Lin, CP;Stabin, MF
寻找用于全身放射治疗的理想放射性同位素的工作仍在继续。作为一种发生器产生的放射性同位素，发射β和γ射线，并具有16.9小时的短物理半衰期，γ-188是一个非常好的潜在候选人全身放射治疗。本研究用Re-188标记羟乙叉二膦酸盐（HEDP），观察其在大鼠体内的生物分布和骨吸收，以评价其临床应用的可能性。（0.4 mCi）Re-188-HEDP，体积为0.1 ml，然后在1 h、24 h或48 h处死（每次4只大鼠）。采集肺、肝、肾、脾、睾丸、肌肉、粪便和骨（胸椎）样品（约0.1 g），并仔细称重。此外，处死后立即从心脏抽取1 ml血样，从膀胱抽取1 ml尿液。计算组织浓度并表示为每克或每毫升注射剂量百分比（% ID/g或ml）。在三只家兔的右胫骨中创建骨损伤，以计算损伤与正常摄取的比率（L/N比率）。生物分布数据显示，骨组织中的放射性在1h时高达1.877% ID/g，在4h时攀升至2.017% ID/g。肾脏中的活性水平在1小时时最高，但在整个研究期间迅速下降。肺、肝、肌肉、脾、睾丸、血液和粪便中的放射性在1h时均低于0.3%ID/g，并且也迅速下降。骨中的生物半衰期最长（60.86 h）。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）。在整个研究期间，肌肉、脾脏、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Re-188-HEDP的家兔的L/N比为4.23 +/-0.21，注射锝-99m亚甲基二膦酸盐的家兔的L/N比为4.25 +/-0.23。总之，我们认为Re-188-HEDP是治疗骨转移瘤的一个非常好的潜在候选药物，因为它具有以下特点：（1）它是发生器产生的;（2）它具有短的半衰期;（3）它发射的γ射线适合于成像;（4）在骨骼系统和骨病变中具有高度选择性摄取;和（5）它在非骨组织中具有低的非靶摄取和快速清除。
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 Re-188 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) Re-188-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 mi 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 Re-188-HEDP and 4.25 +/- 0.23 in those injected with technetium-99m methylene diphosphonate. In conclusion, we would suggest that Re-188-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.