Simple new method for effective concentration of Re-188 solutions from alumina-based W-188-Re-188 generator

Re-188 is a useful generator-produced radioisotope currently under evaluati on for a variety of therapeutic applications, including bone pain palliatio n and intravascular radiation therapy. Because the W-188 parent is availabl e only in a relatively low specific activity (<0.15-0.19 GBq/mg) from react or irradiation of enriched W-186, relatively large volumes of 0.9% saline ( >15 mL) are required for elution of the 188Re daughter from traditional alu mina-based W-188-Re-188 generators. Because these large bolus volumes resul t in solutions with a relatively low specific volume activity of Re-188 (<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 inst ead of saline for generator elution. Methods: After generator elution, the ammonium acetate generator eluent (15-20 mt) is passed through a tandem IC- H Plus cation (Dowex-H)-anion (QMA Light) column system. Exchange of ammoni um cations with hydrogen ions on the cation column forms an acetic acid sol ution containing perrhenate anions from which the macroscopic levels of the acetate anion of the eluent have been effectively removed. Because perrhen ic acid is fully dissociated at this pH, the QMA Light column specifically traps the Re-188-perrhenate, which is subsequently eluted with a low volume (<1 mt) of saline. Concentration ratios greater than 20:1 are readily achi eved with this method. Results: A typical clinical-scale generator loaded w ith 19.2 GBq W-188 was used to validate the approach. Saline elution provid ed 188Re in a 75%-80% yield. Although elution with 0.15 mol/L NH4OAc gave l ower yields (55%-60%), use of 0.3 mol/L NH4OAc provided yields comparable w ith those of saline (70%-75%). W-188 parent breakthrough was not detected a fter passage of the bolus through the tandem concentration system. Bolus vo lumes of 15-20 mt, which initially contained as much as 11.1-14.8 GBq Re-18 8, were readily concentrated to less than 1 mt saline using QMA Light cartr idges. The generator was evaluated for more than 3 mo with no decrease in p erformance. Conclusion: This approach represents a simple, rapid, and effec tive method using inexpensive disposable components of concentrating soluti ons of Re-188 for preparation of therapeutic agents.