ABSTRACT
Background & objectives: The prerequisite of radioimmunotherapy is stable binding of a radionuclide to monoclonal antibodies, which are specific to the tumour-associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of the tumour cells, making it a suitable target for therapeutic radioactive monoclonal antibodies. In the present study, the immunoconjugate of biosimilar Rituximab (Reditux™) and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and radiolabelled with Lutetium-177 followed by quality control procedures. Methods: Rituximab(BioSim) was desalted with sodium bicarbonate (0.1M, pH 9.0) and incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was evaluated by determining the number of chelators per antibody molecule. This conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The quality control parameters like pH, clarity, radiochemical purity, in vitro stability and sterility were studied. Immunoreactivity of 177Lu-DOTA-Rituximab (BioSim) was assessed using RAMOS cells. The radioimmunoconjugate (RIC) after stringent quality assurance was injected in three patients and the biodistribution profile was analysed. Results: An average of 4.25 ± 1.04 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab (BioSim).The radiochemical purity of the labelled antibody was >95 per cent with preserved affinity for CD20 antigen. The final preparation was stable up to about 120 h when tested under different conditions. A favourable biodistribution profile was observed with liver showing the maximum uptake of the RIC. Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177Lu-DOTA-antiCD20 antibody-Rituximab (BioSim) in patients of relapsed and refractory non Hodgkin’s lymphoma can be considered.
ABSTRACT
Background & objectives: Hyperhomocysteinaemia (HCA) either due to mutation of MTHFR gene or deficiency of vitamin B12 and folic acid, has been reported as a risk factor for coronary artery disease (CAD). The present study was aimed to determine plasma homocysteine (Hcy) levels and to evaluate MTHFR C677T gene polymorphism as risk factors for CAD, and to study the role of Hcy in conjunction with a few other risk factors of CAD in young Indians. The effect of vitamin B12 and folic acid supplements on the raised plasma Hcy levels in patients of CAD was also assessed. Methods: The present study included 199 consecutive angiography confirmed CAD patients, <45 yr of age, without any other known pro- coagulant state and 200 age- and sex-matched healthy controls. Fasting blood samples were collected in EDTA and plasma Hcy was estimated by ELISA test and the MTHFR C677T polymorphism detection was carried out by PCR-RFLP method. Results: Significant difference (P<0.001) was found between mean fasting levels of plasma Hcy in cases (22.14 ± 10.62 μmol/l) and controls (17.38 ± 8.46 μmol/l) with an Odds ratio as 1.93 (95% CI, 1.27-2.94). Levels of cholesterol, LDL, and triglycerides were significantly (P<0.001) higher in cases compared with controls. Interpretation & conclusions: Our study showed significant correlation between hyperhomocysteinaemia and coronary artery disease. Multivariate analysis by logistic regression of the various risk factors of CAD, found high levels of Hcy, cholesterol, LDL and low levels of HDL and smoking as independent predictors of CAD when all other factors were controlled. Significant post-treatment decrease found in HCA was easily modifiable by vitamin intervention irrespective to their CT or TT genotype of C677T MTHFR gene. Further studies to look at the plasma levels of folate and cobalamines and their association with Hcy are required to be done.
Subject(s)
Angiography , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay , Homocystine/physiology , Humans , Methylenetetrahydrofolate Reductase (NADPH2)/physiology , India/epidemiology , Risk Factors , Polymorphism, Genetic , Young AdultABSTRACT
Haemorrhagic Septicaemia (HS), an acute and fatal disease of cattle and buffalo is primarily caused by serotype B:2 or E:2 of Pasteurella multocida. The transferrin binding protein A (TbpA) has been found to act as immunogen and potent vaccine candidate in various Gram negative bacteria including P. multocida. The present study was carried out to evaluate the potential of this antigen as a DNA vaccine against HS in mice model. The tbpA gene of P. multocida serotype B:2 was cloned in a mammalian expression vector alone and along with murine IL2 gene as immunological adjuvant to produce monocistronic and bicistronic DNA vaccine constructs, respectively. The immune response to DNA vaccines was evaluated based on serum antibody titres and lymphocyte proliferation assay. A significant increase in humoral and cell mediated immune responses was observed in mice vaccinated with DNA vaccines as compared to non immunized group. Additionally, the bicistronic DNA vaccine provided superior immune response and protection level following challenge as compared to monocistronic construct. The study revealed that DNA vaccine presents a promising approach for the prevention of HS.
ABSTRACT
Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a rare type of cancer that can arise from the diffused endocrine system, located in the gastrointestinal (GI) tract (carcinoids) and in the pancreas (insular tumors). Approximately 2% of all malignant tumours of the gastrointestinal system are GEP-NETs which can express somatostatin receptors. 111In-pentetreotide (octreoscan) and 68Ga-DOTA NOC (68Ga-labelled [1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-Octreotide) are the commonly used radiopharmaceuticals for imaging. Once localized using 68Ga DOTA NOC or octreoscan, these tumours can be successfully targeted with radiolabelled somatostatin analogues. This review focuses on common nuclear medicine procedures used in both imaging and treatment of these tumors.