Evaluating the potential of 188Re-SOCTA–trastuzumab as a new radioimmunoagent for breast cancer treatment

IntroductionRadioimmunotherapy, which utilizes monoclonal antibodies and therapeutic radioisotopes against antigen-expressing tumor tissues, is an attractive therapeutic approach for cancer therapy. Trastuzumab (Herceptin) is a humanized anti-HER-2/neu monoclonal antibody for breast cancer treatment. In this paper, we introduce a new radioimmunoagent, 188Re-trastuzumab, via a bifunctional ligand, succinimidyl 3,6-diaza-5-oxo-3-[2-((triphenylmethyl)thio)ethyl]-8-[(triphenylmethyl)thio]octanoate (SOCTA), and evaluate its potential to be a therapeutic radiopharmaceutical for breast cancer treatment.MethodsEquimolar amounts of SOCTA and trastuzumab were selected to react, and the conjugation ratio of SOCTA–trastuzumab was evaluated by the MALDI-TOF method. The immunoreactivity of SOCTA–trastuzumab was compared with nonconjugated trastuzumab in HER-2/neu overexpressing human breast cancer cell BT-474. Biodistribution experiment and microSPECT/CT images of 188Re-SOCTA–trastuzumab being administered intravenously to SCID mice bearing xenografted BT-474 breast cancer were investigated to evaluate the tumor-targeting capability.ResultsThe covalent attachment of SOCTA to trastuzumab (at 1:1 molar ratio) resulted in the averaged conjugation ratio of 0.27±0.06 (n=3). The complex could easily be labeled with 188Re and achieve 95% radiochemical purity (RCP) after 1 h of reaction at room temperature. The in vitro stability study also revealed that the RCP of 188Re-SOCTA–trastuzumab was at a value of more than 85% after 48 h of incubation with human serum. The immunoreactivity evaluation showed that SOCTA–trastuzumab and nonconjugated trastuzumab had similar binding capacity (Bmax) to HER-2/neu receptor in BT-474 cells. The animal experiments showed that 188Re-SOCTA–trastuzumab accumulated more intensively in the tumor site as compared to normal tissue.ConclusionWe suggest that 188Re-SOCTA–trastuzumab could be a potential candidate for radioimmunotherapy.