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  • Title: Availability of rhenium-188 from the alumina-based tungsten-188/rhenium-188 generator for preparation of rhenium-188-labeled radiopharmaceuticals for cancer treatment.
    Author: Knapp FF, Beets AL, Guhlke S, Zamora PO, Bender H, Palmedo H, Biersack HJ.
    Journal: Anticancer Res; 1997; 17(3B):1783-95. PubMed ID: 9179235.
    Abstract:
    Rhenium-188 (beta- = 2.2 MeV; gamma = 155 keV; T1/2 16.9 hours) is an attractive therapeutic radioisotope which is produced from decay of the reactor-produced tungsten-188 parent (T1/2 69 days) and thus conveniently obtained on demand by elution from the alumina-based tungsten-188 /rhenium-188 generator system. The rhenium-188 is obtained as sodium perrhenate by elution of the generator with 0.9% saline. The post elution use of disposable tandem, ion-exchange columns is a simple method for the concentration of rhenium-188 saline solutions with specific volumes > 500 mCi/ml. This method can also extend the useful shelf-life of the generator, which can be as long as one year. The long useful shelf-life of the generator is expected to provide rhenium-188 at very reasonable costs for routine preparation of a variety of radiopharmaceuticals for the treatment of a variety of cancers including breast cancer. We are evaluating two types of Re-188-labeled agents under investigation which have potential for the treatment of breast cancer. Rhenium-188-labeled hydroxyethylidenediphosphonate (HEDP) and Re-188-dimercaptosuccinic acid (DMSA) are being applied for palliative treatment of pain associated with skeletal metastases, and the Re-188-RC-160 somatostatin analogue [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Lys-Val-Cys-Trp-NH2] for somatostatin-receptor-positive tumors. The results of initial clinical studies with the two bone pain agents demonstrate good targeting 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 patients with prostate cancer, similar results are expected in planned studies in breast cancer patients. In animal studies, Re-188-RC-160 has been successfully used for the local/regional treatment of experimental breast cancer and other cancers. Re-188-RC-160 binds to somatostatin-receptor-positive cells both in vitro and in vivo, including breast cancer cells (ZR-75-1 breast carcinoma and NCI-H69 human small cell ling carcinoma), but not to binding-negative cells (Raji, Burkitt's lymphoma). A structurally similar Re-188-cyclic peptide with different binding specificity (CTOP [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Orn-Thr-Pen-Thr-ol]; an opiate-receptor antagonist) did not bind to target cells. 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 significantly reduce radiolytic degradation of the somatostatin peptide analogues, and may have general application in the stabilization of Re-188-labeled radio-pharmaceuticals.
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