Guhlke S, Beets A L, Oetjen K, Mirzadeh S, Biersack H J, Knapp F F
Nuclear Medicine Program, Life Sciences Division, Oak Ridge National Laboratory, Tennessee 37831-6229, USA.
J Nucl Med. 2000 Jul;41(7):1271-8.
(188)Re is a useful generator-produced radioisotope currently under evaluation for a variety of therapeutic applications, including bone pain palliation and intravascular radiation therapy. Because the (188)W parent is available only in a relatively low specific activity (<0.15-0.19 GBq/mg) from reactor irradiation of enriched (186)W, relatively large volumes of 0.9% saline (>15 mL) are required for elution of the (188)Re daughter from traditional alumina-based (188)W-(188)Re generators. Because these large bolus volumes result in solutions with a relatively low specific volume activity of (188)Re (<1 GBq/mL for the 18.5-GBq generator), the availability of effective methods for eluent concentration is important. Our new approach is based on the use of 0.3 mol/L ammonium acetate as a representative salt of a weak acid instead of saline for generator elution.
After generator elution, the ammonium acetate generator eluent (15-20 mL) is passed through a tandem IC-H Plus cation (Dowex-H)-anion (QMA Light) column system. Exchange of ammonium cations with hydrogen ions on the cation column forms an acetic acid solution containing perrhenate anions from which the macroscopic levels of the acetate anion of the eluent have been effectively removed. Because perrhenic acid is fully dissociated at this pH, the QMA Light column specifically traps the (188)Re-perrhenate, which is subsequently eluted with a low volume (<1 mL) of saline. Concentration ratios greater than 20:1 are readily achieved with this method.
A typical clinical-scale generator loaded with 19.2 GBq (188)W was used to validate the approach. Saline elution provided (188)Re in a 75%-80% yield. Although elution with 0.15 mol/L NH4OAc gave lower yields (55%-60%), use of 0.3 mol/L NH4OAc provided yields comparable with those of saline (70%-75%). (188)W parent breakthrough was not detected after passage of the bolus through the tandem concentration system. Bolus volumes of 15-20 mL, which initially contained as much as 11.1-14.8 GBq (188)Re, were readily concentrated to less than 1 mL saline using QMA Light cartridges. The generator was evaluated for more than 3 mo with no decrease in performance.
This approach represents a simple, rapid, and effective method using inexpensive disposable components of concentrating solutions of (188)Re for preparation of therapeutic agents.
(188)铼是一种有用的由发生器产生的放射性同位素,目前正在评估其在多种治疗应用中的价值,包括缓解骨痛和血管内放射治疗。由于(188)钨母体仅能通过富集(186)钨的反应堆辐照获得相对较低的比活度(<0.15 - 0.19 GBq/mg),从传统的基于氧化铝的(188)钨 - (188)铼发生器中洗脱(188)铼子体需要相对大量的0.9%生理盐水(>15 mL)。因为这些大剂量体积导致(188)铼溶液的比体积活度相对较低(对于18.5 GBq的发生器,<1 GBq/mL),所以有效的洗脱液浓缩方法很重要。我们的新方法基于使用0.3 mol/L醋酸铵作为弱酸的代表性盐代替生理盐水进行发生器洗脱。
发生器洗脱后,将醋酸铵发生器洗脱液(15 - 20 mL)通过串联的IC - H Plus阳离子(Dowex - H) - 阴离子(QMA Light)柱系统。阳离子柱上铵离子与氢离子交换形成含有高铼酸根阴离子的醋酸溶液,洗脱液中的醋酸根阴离子宏观水平已被有效去除。由于高铼酸在该pH下完全解离,QMA Light柱特异性捕获(188)铼 - 高铼酸盐,随后用少量(<1 mL)生理盐水洗脱。用这种方法很容易实现大于20:1的浓缩比。
使用一个典型的装载19.2 GBq(188)钨的临床规模发生器来验证该方法。生理盐水洗脱的(188)铼产率为75% - 80%。虽然用0.15 mol/L NH4OAc洗脱产率较低(55% - 60%),但使用0.3 mol/L NH4OAc提供的产率与生理盐水相当(70% - 75%)。大剂量溶液通过串联浓缩系统后未检测到(188)钨母体穿透。最初含有高达11.1 - 14.8 GBq(188)铼的15 - 20 mL大剂量溶液,使用QMA Light柱很容易浓缩至小于1 mL生理盐水。对该发生器进行了3个多月的评估,性能没有下降。
这种方法代表了一种简单、快速且有效的方法,使用廉价的一次性组件浓缩(188)铼溶液以制备治疗剂。