Development of Radiopharmaceutical Formulations for Imaging of Non Hodgkin's lymphoma

Abstract

Non Hodgkin's Lymphoma (NHL) is the most common subtype of lymphoma, which consists of tumour cells originating from B lymphocyte cells. Burkitt's lymphoma is one of the most common subtypes of NHL, and it is one of the most common type, especially in children. Treatment, diagnosis and imaging can be obtained by targeting the CD20 epitope, which is available on the surface of B lymphocytes and shows increased expression. In this study, CD20 specific, new generation humanized-monoclonal antibody “Obinutuzumab” was radiolabelled with 89Zr and formulations were developed. In-vitro and in-vivo studies were carried out with the optimum formulation determined as a result of quality control tests among these developed formulations. Ramos cells (CD20(+)) were used to establish Burkitt's lymphoma in in-vitro and in-vivo studies, while HL60 (CD20(-) ) cells were used as the control group. In order to determine the in-vitro activity of 89Zr-Obinutuzumab, immuno-reactivity and binding constant studies were performed. Immuno-reactivity studies were performed on Ramos and HL60 cells using 89Zr-Obinutuzumab and 89Zr-Tocilizumab (control) formulations. Following the data obtained here, binding constant studies of the 89Zr-Obinutuzumab formulation were conducted on Ramos cells. In the light of the data obtained from in-vitro studies, in-vivo studies were started. In-vivo studies were performed on 3 groups of female SCID mice by taking PET/CT images and completing biodistribution studies. The resulting data showed that the labeling efficiency and stability of 89Zr-Obinutuzumab were high. In the light of in-vitro studies, immuno-reactivity (%) and binding constant values were found promising for 89Zr-Obinutuzumab formulation. Although the results obtained from in-vivo studies were not as high as expected, it suggested that the 89Zr-Obinutuzumab formulation is a promising agent for lymphoma and requires further research.