Evaluating the therapeutic potential of 188Re-HYNIC-trastuzumab(Herceptin) for human breast cancer in the animal model

Objectives Her-2/neu protein over expression has been identified in 10%~34% of invasive breast cancers. Trastuzumab(Herceptin) is a humanized IgG1 monoclonal antibody that recognizes HER-2/neu receptor. We developed a new therapeutic radiopharmaceutical ¹⁸⁸Re-labelled trastuzumab (Herceptin) through a bifunctional chelator, hydrazine nicotinamide (HYNIC). We test the ability of ¹⁸⁸Re-HYNIC-Herceptin complex to recognize the Her-2/neu which over expression in human breast cancer cell in vitro and in vivo.

Methods We synthesized HYNIC-Herceptin and labeled with Re-188. The immunoreactivity of HYNIC-Herceptin was evaluated by a receptor-binding assay using BT-474 human breast cancer cell line. Biodistribution, microSPECT/CT imaging and therapeutic efficacy experiments were performed in female SCID mice bearing BT-474 human breast cancer cell line. We treated these mice ¹⁸⁸Re-HYNIC-trastuzumab(Herceptin) once two weeks and tumors were measured for length, width, and height once a week for 4 month.

Results The biodistribution data show that the tumor uptake of radioactivity increased from 0.4±0.22 %ID/g at 1h to 2.1±0.97 %ID/g at 48h postinjection of ¹⁸⁸Re-HYNIC-trastuzumab (Herceptin). MicroSPECT /CT images show that tumor uptake is visualized as well as high accumulation in the tumor, kidneys and spleen. Therapeutic efficacy tumor size measurements showed that tumor growth was significantly inhibited by treating with ¹⁸⁸Re-HYNIC-trastuzumab(Herceptin).

Conclusions This study proved that ¹⁸⁸Re-HYNIC-Herceptin is a potential therapeutic radiopharmaceutical for breast cancer. We still need to perform more advanced studies to prove its efficacy.