AVAILABILITY OF RE-188 FROM THE ALUMINA-BASED TUNGSTEN-188 RHENIUM-188 GENERATOR FOR PREPARATION OF RHENIUM-188-LABELED RADIOPHARMACEUTICALS FOR CANCER-TREATMENT/

Rhenium-188 (beta- = 2.2 MeV; gamma- = 155 keV; T-1/2 16.9 hours) is a n attractive therapeutic radioisotope which is produced from decay of the reactor produced tungsten-188 parent (T1/2 69 days) and thus conve niently obtained on demand by elution fi om the alumina-based tungsten -188 /rhenium-188 generator system. The rhenium-188 is obtained as sod ium perrhenate by elution of the generator with 0.9% saline. The post elution use of disposable tandem, ion-exchange columns is a simple met hod for the concentration of rhenium-188 saline solutions with specifi c volumes > 500 mCi/ml. This method can also extend the useful shelf-l ife of the generator, which can be as long as one year. The long usefu l shelf-life of the generator is expected to provide rhenium-188 at ve ry reasonable costs for routine preparation of a variety of radiopharm aceuticals for the treatment of a variety of cancers,including breast cancer. We are evaluating two types of Re-188-labeled agents under inv estigation which have potential for the treatment of breast cancer. Rh enium-188-labeled hydroxyethylidenedophosphonate (HEDP) and Re-188-dim ercaptosuccinic acid (DMSA) are being applied for palliative treatment of pain associated with skeletal metastases, and the Re-188-RC-160 so matostatin analogue [cyclic NH2-(D)-Phe-Cys- Try-(D)-Trp-Lys-Val-Cys-T rp-NH2] for somatostatin-receptor-positive tumors. The results of init ial clinical studies with the two bone pain agents demonstrate good ta rgeting to skeletal metastases, and use of Re-188-HEDP has resulted in . pain palliation with minimal bone marrow suppression in the initial patient studies. While these initial studies have been conducted in pa tients with prostate cancer; similar results are expected in planned s tudies in breast cancer patients. In animal studies, Re-188-RC-160 has been successfully used for the local/regional treatment of experiment al breast cancer and other cancers. Re-188-RC-160 binds to somatostati n-receptor- positive cells both in vitro and in vivo, including breast cancer cells (ZR-75-1 breast carcinoma and NCI-H69 human small cell l ing carcinoma), but not to binding-negative cells (Raji, Burkitt's lym phoma). A structurally similar Re-188-cyclic peptide with different bi nding specificity (CTOP [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Orn-Thr-Pe n-Thr-ol]; art opiate-receptor antagonost) did not bind to target cell s. Both gentisic acid and ascorbic acid are present in the Re-188-HEDP and Re-188-RC-160 formulations and have been found to also significan tly reduce radiolytic degradation of the somatostatin peptide analogue s, and may have general application in the stabilization of Re-188-lab led radiopharmaceuticals.