Imaging Evaluation of Multi-type Neuropeptide Y(NPY) Derivative for Breast Tumor Therapy

2019 Objectives: Peptide Receptor Radionuclide Therapy (PRRT) is a widely known molecular targeted therapy. PRRT is performed by using a small peptide which is combined with therapeutic radionuclides. We tried to develop a multimodality compound for both PRRT and Boron Neutron capture therapy (BNCT), and also both the binding affinity and the ratio of tumor to normal tissue (T/N) of boron drug will be high than traditional BNCT drugs. We selected peptide-NPY derivative, modified with BSH analogue, as a multimodality drug for BNCT. Neuropeptide Y (NPY) is a 36-amino acid peptide and regulates in various physiological functions through its four receptors. Its receptors are a family of G protein-coupled receptors and can be divided into five subtypes.The aims of this study was to synthesize a long-circulated NPY derivative and evaluate tumor image of the MCF-7 and 4T1 animal model as a candidate for breast cancer therapy. Methods: We synthesized DOTA-Boron-ENPY, which is a 16-amino acid NPY derivative. In our research strategy, we used the recombination of EB(Albumin affinity compound), DOTA, BSH and breast cancer targeted NPY-peptide as the pharmacophore for BNCT, once label with In-111 for PRRT. 30-60μg DOTA-Boron-ENPY peptide reacted with 6mCi indium-111 chloride (from INER) at 95℃ within 15min. The radiochemical purity was detected by Radio-HPLC. In animal study, tumor xenografts were performed in 6-wk-old female BALB/c mice by subcutaneous injection of2[asterisk]106 4T1 cells, and nanoSPECT/CT imaging was performed at 0.5 h to 96h after injecting of the 111In-DOTA-Boron-ENPY.Results: The radiochemical purity of 111In-DOTA-Boron-ENPY was greater than 90%. In vivo study, MCF-7 animal tumors uptake was greater than 7% ID/g in 72 hours post-injection for111In-DOTA-Boron-ENPY. In the 4T1 animal model, tumors uptake was greater than 30% ID/g in 48 hours post-injection for111In-DOTA-Boron-ENPY. It also has a high tumor to muscle ratio (T/M) greater than 4. Conclusions: From the in vivo study, we consider the DOTA-Boron-ENPY as a long circulation radiopharmaceutical candidate for companion diagnostics (CDx). It can be a potential candidate drug in breast tumor for BNCT.