Radiolabeled biomolecules with 186Re: potential for radioimmunotherapy

Rhenium-186 has been theoretically determined to be among the best therapy radiolabels due to its unique half-life, particulate and gamma emissions and chelation properties. Traditionally, rhenium chelates have been synthesized by the tin reduction method at low pH which frequently produces denaturation of acid labile proteins. A comparative study has been carried out to assess three techniques of reducing 186ReO-4 in order to label biologically active macromolecules (i.e. human serum albumin (HSA), anti-human serum albumin antibody (HSA-Ab) and a monoclonal antibody to T-cells [T-101]). These experiments showed that stannous and dithionite reduction methods provide for an overall labeling yield of between 5 and 18% with an associated immunoreactivity of 12-40%. The hypophosphorous acid (H3PO2) reduction method, however, yielded no usable radiolabeled product. The preparation of 186Re-DTPA-HSA produced an 18.2% radiochemical yield (7.4 X 10(6) Bq/mg) and 40% retention of binding affinity. Using the stannous or dithionite reduction methods for the radiolabeling of HSA-Ab and T-101 resulted in a relatively low yield (9%), but the labeled product retained binding affinity of 12.25% with Protein A.