Development of Radiopharmaceutical Formulations for Imaging of Non-Hodgkin's Lymphoma
Tez Türü: Doktora
Tezin Yürütüldüğü Kurum: Hacettepe Üniversitesi, Sağlık Bilimleri Enstitüsü, Radyofarmasi A.B.D., Türkiye
Tez Danışmanı: Prof. Dr. Asuman Yekta Özer, Prof. Dr. Neıl Hartman
Tezin Onay Tarihi: 2022
Tezin Dili: Türkçe
Özet:
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, invivo
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.