Introduction: Antibodies with specificity towards tumour antigens can be labelled with radionuclides to enable diagnostic imaging (e.g. SPECT or PET) or to improve therapeutic efficiency. Combining beta-particle and gamma emission effect with therapeutic properties of C225 monoclonal antibody, Cetuximab (Erbitux, Merck Pharmaceuticals) was targeted in this study.Methods: The C225 antibody was labeled with 170Tm-Thulium chloride (100 MBq) after conjugation with in-house freshly prepared 1, 4, 7, 10-tetraazacyclododecane-N, N, N, N-tetraacetic acid mono- (Nhydroxysuccinimidyl) ester (DOTA-NHS). Conjugated-cetuximab was obtained by the addition of 0.5 ml of a cetuximab pharmaceutical solution (1 mg, in phosphate buffer, pH=8) to a glass tube precoated with freshly prepared DOTA-NHS (~5 mg) at 25°C.170Tm-Thulium chloride was obtained by a thermal neutron flux (3-4 × 1013 n•cm–2•s–1) of a natural thulium nitrate sample, dissolved in acidic media. Radiolabeling was performed in 2-3 hours by the addition of DOTA-NHS-Cetuximab conjugate at room temperature.Results: Radiochemical purity of 92% (ITLC, DTPA 1mM) was obtained for the final radioimmunoconjugate (specific activity=72 TBq/mmol). Biodistribution studies in normal rats were performed to determine radioimmunoconjugate distribution up to 24 h. Stability of radiolabeled protein in presence of human serum was tested at 37 C for up to 72h and it was observed that the botained formulation is stable even up to one month after preparation.Conclusion: For [170Tm] -DOTA-NHS-Cetuximab, the radiochemical purity was 92% and the labeling and quality control took less than 1 h. The radiolabeled complex was stable in human serum for at least 72 h and no significant amount of free 170Tm as well as 170Tm-DOTA-NHS was observed. The final preparation was administered to normal rats and biodistribution of the radiopharmaceutical was checked 2-168 h later. The prepared radio-labeled cetuximab using 170Tm can be applied to improve the therapeutic potential of (epidermal growth factor receptor) EGFR -targeted drugs. The use of these selective labeled agents in nuclear medicine applications may facilitate in vivo EGFR-targeted drug efficacy.

Background: The main purpose of radioimmunotherapy is delivered lethal dose to the tumor cells which depends on the immunological and pharmacological of the antibody (Ab) property and the conjugated radionuclide characteristics. Objectives: The aim of this study is preparation of DOTA-Rituximab complex and radiolabeling with Lu-177 and comparison with the results of 131I-Rituximab radiolabed with Chloramine-T method that was obtained before. Methods: The number of chelator molecules (DOTA) attached to the DOTA-Rituximab complex was determined by Arsenazo III reagent. After radiolabeling with Lu-177, the stability in normal saline and the biodistribution in the healthy mice was evaluated. The Immunoreactivity of Ab was checked on Raji cell lines and the results were compared with 131I-Rituximab. Results: Each 300  g of antibody was labeled with 6 mCi Lu-177. After 48 hours, 82% of the radiolabeled antibody was stable and about 18% of the radiotracer was in the blood. The immunoreactivity was calculated 85%  2%. Conclusions: The results showed that radiolabeling with Lu-177 was done with higher yield than iodine-131 and the produced radiopharmacy has more stability and immunoreactivity. The biodistribution results were acceptable in both radiopharmacy.

This work presents a comparative biological evaluation of 90Y- and 177Lu- labelled DOTA-SCN and DOTA-NHS conjugated to Rituximab in tumour-bearing mice. Two DOTA derivatives, p-SCN-Bn-DOTA and DOTA-NHS-ester were conjugated to Rituximab and then freeze-dried kit formulations were prepared, as previously described (1). Tissue distribution was investigated in tumour-bearing (Raji s.c.) male Rj: NMRI-Foxn1nu/Foxn1nu mice at different time points after administration of 177Lu-DOTA-Rituximab or 90Y-DOTA-Rituximab (6 MBq/10 mg per mouse). In addition, tumour images were acquired with a PhotonIMAGERTM after injection of 90Y-DOTA (SCN) -Rituximab. All radioimmunoconjugates were obtained with high radiolabelling yield (RCP>98%) and specific activity of ca.0.6 GBq/mg. The conjugates were stable in human serum and in 0.9% NaCl; however, progressive aggregation was observed with time, in particular for DOTA- (SCN) conjugates. Both 177Lu- and 90Y-DOTA - (SCN) -Rituximab revealed slow blood clearance. The maximum tumour uptake was found 72 h after injection of 177Lu-DOTA- (SCN) -Rituximab (9.3 ID/g). A high radioactivity uptake was observed in liver and spleen, confirming the hepatobiliary excretion route. The results obtained by the radioactive optical imaging harmonize with those from the biodistribution study.

Introduction: 177Lu is a beta emitter with suitable decay mode [T1/2=6.7 d, Eβmax=497 keV, EY=112keV (6.4%) & 208 keV (11%)] for using in radio therapy. Various radiolabeled monoclonal antibodies have been developed in treatment. Rituximab is a chimeric mouse-human monoclonal antibody. Rituximab binds with human B-lymphocate-restricted differentiation antigen: CD20. Rituxsimab was used successfully as an anti-CD20 radiolabeled antibody before.Methods: 177Lu was produced by thermal neutron irradiation of 1 mg of natural Lu2O3 with 4*10^13 n cm-2 s-1 neutron flux at Tehran Research Reactor. The irradiation target was dissolved in 200 mL of 1.0 M HCl, to prepare 177LuCl3. The radionuclide purity of product was measured by using ITLC and gamma spectroscopy by HPGe detector. The macrocyclic bifunctional chelating agent, N-succinimidyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA-NHS) was prepared at 25 C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-Rituximab was obtained by the adding 0.5 mL of a rituximab pharmaceutical solution (10 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01–0.1 mg) at 25C with continuous mild stirring for 15 h. The stability of radiolabeled was studied in human serum. The biodistributions of 177Lu-DOTA-Rituximab and 177LuCl3 were determined for normal rats. The tissue uptakes of each injection were measured.Results: Radiolabeling was performed at 37C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of>98% at optimized conditions. The percents of Injected Dose per gram of tissue were compared in different selected times (2-168 h). The peak of uptakes for 177LuCl3 was observed in bone, liver and kidney. High uptakes of 177Lu-DOTA-Rituximab were in spleen, liver and lungs.Conclusion: The radiolabeled complex was stable in human serum at 37C for 24 h. The biodistribution of the radiolabeled antibody is in agreement with other radiolabeled antiCD20 species already reported.177Lu- DOTA-Rituximab is potential radioimmunotherapeutic agent for B-lymphoma treatment.

Introduction: The importance of existence and application of radiolabeled anti-CD20 monoclonal antibodies at nonmyeloablative doses in treating B-cell NHL is well recognized throughout the world. In this work, Rituximab was successively labeled with 177Lu-lutetium chloride.Methods: Lu-177 chloride was obtained by thermal neutron flux (4 × 1013 n.cm-2.s-1) of natural Lu2O3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, Nsuccinimidyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA-NHS) was prepared followed by conjugation. The radioimmunoconjugate was analyzed for integrity by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Stability of 177Lu-DOTA-rituximab in PBS was determined by storing the final solution at 4°C for 14 days and performing frequent ITLC analysis to determine radiochemical purity followed by administration to wild-type rats for biodistribution studies.Results: DOTA NHS reaction is performed at room temperature and can be done overnight. High uptake in spleen and reticoloendothelial organs was observed. At all time intervals post injection, the activity is mainly removed from the blood which is in agreement with the other reported labeled antibodies. Likewise other radiolabeled proteins the labeled antibody is accumulated in the liver. As a natural reaction to the depletion of the lymphocytes the reticulloendothelial system including spleen will be the final possible reservoir of the depleted lymphocytesConclusion: [177Lu] -DOTA-rituximab is potential radioimmunotherapeutic agent for B-lymphoma treatment.

The National Health Service (NHS) was established in 1948 to provide equitable healthcare for all citizens. Over the years the NHS has gone under different reforms and changes. In 2002 the NHS launched one of its biggest changes in structure since its commencement in 1948. The scale of these changes are greater than those established following the white paper “Working for Patients” in 1989 (Conservative Government) that indicated the introduction of the internal market (focus on efficiency). This review therefore proposes to give a brief summarize of the structural changes and current structure of the NHS in the England. The NHS plan was published in July 2000 (Labour Government) and outlined a 10 year plan of investment in the NHS. This delineates a vision for a service planned around the patients and more responsive to patients’ needs. The Government emphasizes on the empowering of staff at all levels as a way to achieve this vision. "Shifting the Balance of Power" is part of the Government’s plans for implementation of the NHS Plan and has directed to the establishment of new structures. The main feature of change has been giving locally based Primary Care Trusts the role of running the NHS and, with the local authorities, improving health in their areas. The PCTs are receiving 75% of the NHS budget to act as primary services provider, commissioner (service purchaser), network developer and controller. In addition, all former Health Authorities have been abolished and new Strategic Health Authorities (SHA) have been created to serve larger areas and with a more strategic role. The SHAs are responsible for developing strategic frameworks for the local health service; performance of the local health service; and building capacity in the local health service. The Department of Health is also refocusing to reflect these changes, including the abolition of its Regional Offices and relegating some of its operational responsibilities to SHAs and other rganizations. While NHS Trusts (the organizations responsible for running most NHS hospitals, mental health and learning disability services, ambulance services and patient transport) continue to have the similar functions as before, they will have to create new working relationships with PCTs and SHAs. In addition Foundation Trust, which often referred ‘Foundation Hospitals’, were set up in April 2004 and are freestanding hospitals with greater autonomy within the NHS. New structures signify new relationships and partnerships both between NHS organizations and with other stakeholders. All NHS organizations locally - PCTs, Care Trusts and NHS Trusts -are now part of a single structure in which they are supposed accountable to SHAs, which are in turn accountable to Department of Health and ultimately to Secretary of State for Health. Relationships with other collaborators such as Local Authorities and voluntary organizations are also crucial, particularly for PCTs as they work towards improving health and integrating health and social care.