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.