A Process for the Recovery of Strontium from the Urine of Patients Injected with 89 Sr

1. A Process for the Recovery of Strontium from the Urine of Patients Injected with 89Sr Antioco Franco Sedda TRIGA Reactor ENEA Casaccia, Rome, Italy

2. The palliation of pain in patients with metastatic bone cancer represents for the oncologist a difficult clinical problem. The pain is mainly due to the pressure of the tumour mass on the nerve terminations of the periosteum.

3. In these cases, often as a last resource, it can be taken into consideration the use of a radioactive isotope, which is preferentially deposited in the osseous lesions, and palliates the pain for relatively long periods, without important harmful effects on the patient.

4. In the human organism ionic Strontium shares the same physiological pathway as Calcium, and is deposited in the mineral structure of bone, preferentially in regions of high metabolic turn-over, like those adjacent to metastatic lesions.

5. 89Sr is usually administered by intravenous injection of 110-180 MBq, with a specific activity of 3-6 MBq mg-1 of Sr, as SrCl2. The fraction of 89Sr not fixed in the body is eliminated mainly by the kidneys, with a biological T 1/2 of about 14 days. On the metastatic lesions a T 1/2 >> 50 days is observed.

6. After each administration of the isotope, the urine of the patient, which contains up to 80% of the isotope, is collected in the hospital for 15-20 days, stored in hot tanks , and sent for disposal as radioactive waste.

7. Given the relevant cost of 89Sr (2500$/150 MBq) and the high additional cost for the disposal of wastes, a simple chemical process was developed, which permits the recovery and purification of 89Sr eliminated in the urine in a form suitable for further clinical use. At the end of the process [89Sr] SrCl2 in injectable form is obtained.

8. Operative sequence

9. Lay out of the process

10. Filtration Every 7-10 days the urine of all patients are mixed together, double filtered, poured in a tank, and 1% in volume of 30% H2O2 is added, in order to prevent any fermentation.

11. Precipitation Ca 2+ + Sr 2+ + Mg 2+ + (NH4)3PO4 Ca3(Sr,Mg)(PO4)2  • The pH is raised at 8-9 and a flocculation aid is added. • The reaction is carried out at room temperature. • Human urine usually contains enough calcium to permit the precipitation of Ca3(PO)4

12. Separation by chelating resin • The precipitate is dissolved in in HNO3 8M • The solution is passed through a 2-4 ml “Sr-Spec - EIChrom” chelating resin column, which selectively held Sr, while Ca, Mg and other elements are eluted. • The column is washed with 10 free column volumes of 10M HNO3. • Sr is eluted with 5-10 free column volumes of 0.01 M HNO3 .

13. Conversion into chloride form The Strontium Nitrate is converted into Chloride form by one of the following: • the solution is heated to dryness with concentrated HCl 2-3 times, and 0.9% NaCl is added • the solution, brought to pH 5-7, is passed through a column of Amberlite IR-4B resin in form chloride, and the Strontium is elute with NaCl 0.9%.

14. Sterilisation The SrCl2 is then sterilised by filtration through a sterile 0.2 mm sterile filter. The product is tested for sterility, and apyrogenicity by the Limulus Agglutination Test.

15. Pilot plant for the recovery of 89Sr

16. Characteristics of the process • The final yield of the process for the recovery of 89Sr is 94 + 4%. • The specific activity of the product never exceeded 6MBq/ mg Sr, as determined by NAA. • The volume of urine which can be treated depends only from the plant tank dimension. • The cost of the plant and of the involved reagents is rather low.

17. Simple chemical operations, easily carried out by technical staff of hospital laboratories.

18. Relevant volume reduction of the wastes. For each patient 20 litres became 10 millilitres.

19. If the purified 89Sr is re-injected, a saving of 50% on the cost of the isotope for injection is reached. • The expenses for waste disposal are almost eliminated.