A comparative study of preliminary dosimetry for human based on distribution data in rats with 111In, 90Y, 153Sm, and 177Lu labeled rituximab

Radio immunotherapy is one of the most important and effective therapies for B-cell non Hoddgkin’s lymphoma treatment. Today, anti CD-20 antibodies labeled with beta emitter radionuclides are used in radio immunotherapy. Various radionuclides for labeling anti CD-20 antibodies have been studied and developed for the treatment and diagnosis of malignancies. This paper describes the preparation, bio-distribution and absorbed dose rate of 111In, 90Y, 177Lu, and 153Sm labeled anti CD-20 antibodies (rituximab) in human organs, after injection to rats. The macro cyclic bifunctional chelating agent, N-succinimidyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA-NHS) for conjugation to antibody, was used to prepare DOTA-rituximab. The conjugates were purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated and total concentration was determined by spectrophotometric method. Radio-labeling was performed at 40 °C for 24 hours. After the quality control studies, the final radioactive solution was injected intravenously into rats through their tail vein. The tissue uptakes of each injection were measured. Then we calculated S values for 177Lu and 153Sm by using specific absorbed fractions and data used in the manner of radio-labeled analysis and dosimetry for humans. The absorbed dose rate of each organ was calculated in the specific time by medical internal radiation dose method with linear approximation in the activity measurements

Preparation and Quality Control of the [153Sm]-Samarium Maltolate Complex as a Lanthanide Mobilization Product in Rats

Development of lanthanide detoxification agents and protocols is of great importance in management of overdoses. Due to safety of maltol as a detoxifying agent in metal overloads, it can be used as a lanthanide detoxifying agent. In order to demonstrate the biodistribution of final complex, [153Sm]-samarium maltolate was prepared using Sm-153 chloride (radiochemical purity >99.9%; ITLC and specific activity). The stability of the labeled compound was determined in the final solution up to 24h as well as the partition coefficient. Biodistribution studies of Sm-153 chloride, [153Sm]-samarium maltolate were carried out in wild-type rats comparing the critical organ uptakes. Comparative study for Sm3+ cation and the labeled compound was conducted up to 48 h, demonstrating a more rapid wash out for the labeled compound. The effective and biological half lives of 2.3 h and 2.46h were calculated for the complex. The data suggest the detoxification property of maltol formulation for lanthanide overdoses

Production, Quality Control and Pharmacokinetic Studies of 166Ho-EDTMP for Therapeutic Applications

166Ho-EDTMP is a major therapeutic agent which is widely used in bone palliation therapy. In this study, a 166Ho-EDTMP complex was prepared successfully using an in-house synthesized EDTMP ligand and 166HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 1013 ncm−2s−1) of natural Ho(NO3)3 samples (specific activity = 3–5 GBq/mg), dissolved in acidic media. The radiochemical purity of 166Ho-EDTMP was checked by ITLC (>99%) and stability studies in presence of human serum and final preparation were performed. The biodistribution of 166Ho-EDTMP and 166HoCl3 in wild-type rats was checked by scarification. SPECT imaging of 166Ho-EDTMP was also performed in wild-type rats. A comparative accumulation study for 166Ho-EDTMP and 166HoCl3 was performed for vital organs up to 48h. Significant bone accumulation (>70%) of the tracer in 48h was observed

Preparation and quality control of 177 Lu-chitosan for radiosynovectomy

ABSTRACT Introduction: Rheumatoid arthritis (RA) is the most common autoimmune disease, leading to the destruction of the joints and causing pain, disability, and immobility in the patients. Radiosynovectomy (RSV) has been applied as an effective treatment for the patients with resistant synovitis after failure of long-term pharmacotherapy and intra-articular steroid injection for more than 50 years. Several radiopharmaceuticals have been developed for RSV so far, but still development of new radiophamaceuticals is of crucial interest. In this research, the 177 Lu-chitosan complex ( 177 Lu-CHITO) was introduced as a new agent for RSV. Methods: 177 Lu was produced by irradiation of a natural Lu 2 O 3 target at a thermal neutron flux of approximately 4 × 1

Production, biodistribution assessment and dosimetric evaluation of 177Lu-TTHMP as a bone pain palliation agent

Objective(s): Recently, bone-avid radiopharmaceuticals have been shown to have potential benefits for the treatment of widespread bone metastases. Although 177Lutriethylene tetramine hexa methylene phosphonic acid (abbreviated as 177Lu- TTHMP), as an agent for bone pain palliation, has been evaluated in previous studies, there are large discrepancies between the obtained results. In this study, production, quality control, biodistribution, and dose evaluation of 177Lu-TTHMP have been investigated and compared with the previously reported data. Methods: TTHMP was synthesized and characterized, using spectroscopic methods. Radiochemical purity of the 177Lu-TTHMP complex was determined using instant thin-layer chromatography (ITLC) and high performance liquid chromatography (HPLC) methods. The complex was injected to wild-type rats and biodistribution was studied for 7 days. Preliminary dose evaluation was investigated based on biodistribution data in rats. Results: 177Lu was prepared with 2.6-3 GBq/mg specific activity and radionuclide purity of 99.98%. 177Lu-TTHMP was successfully prepared with high radiochemical purity (>99%). The complex showed rapid bone uptake, while accumulation in other organs was insignificant. Dosimetric results showed that all tissues received almost insignificant absorbed doses in comparison with bone tissues. Conclusion: Based on the obtained results, this radiopharmaceutical can be a good candidate for bone pain palliation therapy in skeletal metastases

Investigation of the effects of tumor size and type of radionuclide on tumor curability in targeted radiotherapy

Background: Targeted radiotherapy is one of the important methods of radiotherapy that involves the use of beta-emitting radionuclides to deliver a dose of radiation to tumor cells. An important feature of this method is the tumor size and the finite range of beta particles emitted as a result of radionuclide disintegration those have significant effects for the curability of tumors. Material and Methods: Monte Carlo simulations and mathematical models have been used to investigate the relationship of curability to tumors size for tumors treated with targeted 131I and 90Y. The model assumed that radionuclides are distributed uniformly throughout tumors. Results: The results show that there is an optimal tumor size for cure. For any given cumulated activity, cure probability is greatest for tumors whose diameter is close to the optimum value. There is a maximum value of curability that occurs at a diameter of approximately 3.5 mm for 131I. For 90Y maximum curability occurs at a tumor diameter of approximately 3.5 cm. Tumors smaller than the optimal size are less vulnerable to irradiation from radionuclides because a significant proportion of the disintegration energy escapes and is deposited outside the tumor volume. Tumors larger than the optimal size are less curable because of greater clonogenic cell number. Conclusion: With single radionuclide targeted radiotherapy, there is an optimal tumor size for tumor cure. It is suggested that single agent targeted radiotherapy should not be used for treatment of disseminated disease when multiple tumors of differing size may be present. The use of several radionuclides concurrently would be more effective than reliance on single radionuclide. This approach of using combination of radionuclides with complementary properties could hopefully prepare new measures and improve the efficiency of tumor therapy

Enhancing the Supercapacitive and Superparamagnetic Performances of Iron Oxide Nanoparticles through Yttrium Cations Electro-chemical Doping

<div><p>A one-pot electrosynthesis platform is reported for fabrication of Y3+ doped iron oxide nanoparticles (Y-IONPs). In this procedure, Y-IONPs are electro-deposited from an additive-free aqueous solution of iron(III) nitrate, iron(II) chloride and yttrium chloride. The analysis data provided by X-ray diffraction (XRD), field emission electron microscopy (FE-SEM) and energy-dispersive X-ray (EDX) confirmed that the deposited Y-IONPs sample is composed of magnetite nanoparticles (size≈20nm) doped with about 10wt% Y3+ cations. The performance of the prepared Y-IONPs as supercapacitor electrode material was studied using cyclic voltammetry (CV) and galvanostat charge-discharge (GCD) tests. The obtained electrochemical data showed that Y-IONPs provide SCs as high as 190.3 and 138.9 F g−1 at the discharge loads of 0.25 and 1 A g−1, respectively, and capacity retentions of 95.9% and 88.5% after 2000 GCD cycling. Furthermore, the results of vibrating sample magnetometer measurements confirmed better superparamagnetic behavior of Y-IONPs (Mr=0.32 emu g-1 and HCi= 6.31 G) as compared with pure IONPs (Mr=0.95 emu g-1 and HCi= 14.62 G) resulting from their lower Mr and Hci values. Based on the obtained results, the developed electro-synthesis method was introduced as a facile procedure for the preparation of high performance metal ion doped magnetite nanoparticles.</p></div

Production, Radiolabeling and Biodistribution Studies of 175Yb-DOTMP as Bone Pain Palliation: 175Yb-DOTMP as bone pain palliation

Bone is the third most common site of metastatic disease. Bone pain is the major source of morbidity associated bone metastasis. Bone-seeking radiopharmaceuticals have been applied for many years. The ability to simultaneously treat multiple sites of disease with a more probable therapeutic effect in earlier phases of metastatic disease is one of the advantages of radiopharmaceuticals. 175Yb is oneof the radioisotopes with suitable properties for developing various nuclear medicine agents. Some of these proper properties include 4.2 days half-life, gamma-rays emitted, radionuclidic purity. Radiopharmaceuticals capable of targeting bone tumors generally use phosphonic acid functionality as the targeting moiety. In this direction cyclic tetraphosphonate, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminomethylenephosphonate (DOTMP) has been labeled with 175YbCl3. Production, quality control and biodistribution studies of 175Yb-DOTMP were targeted in this study. 175Yb chloride with mean specific activity of 31 mCi/mg was obtained by thermal neutron flux (3×1013 n.cm-2.s-1) of a natural Yb2O3 sample (isotopic purity of 31.8% for 174Yb) in the Tehran Research Reactor (TRR). Radiolabeling was completed in one h by the addition of DOTMP at room temperature. The radiochemical purity was determined using ITLC and it was more than 98%. The results of biodistribution animal studies are excellent. It was rapidly taken up in the bone in 2 h after injection (ID/g%=3.92) and reminded after 4 d (ID/g%=3.91)