Preparation and quality control of 177Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy

The 177Lu-[tris(1,10-phenanthroline)lutetium(III)] complex (177Lu-PQ3) was prepared successfully with high radiochemical purity (> 99%). Lu-177 chloride was obtained by thermal neutron flux (4 × 1013 n.cm–2.s–1) of natural Lu2(NO3)3 sample, dissolved in acidic media. The radiochemical yield was checked by measuring the radiochemical purity of the 177Lu-PQ complex by ITLC (10 mM DTPA, pH = 5, as mobile phase). The final complex solution was injected intravenously into wild-type male rats and bio-distribution of the complex was checked for up to 48 hours. The dose limiting organs were shown to be the reticulu-endothelial system. The bio-distribution of the labelled compounds in tumour-bearing animals is under investigation. Nuclear Med Rev 2010; 13, 2: 49–5

Preclinical studies of166Ho-chitosan for treatment of hepatocellular carcinoma

Introduction: Recently, due to the special characteristics of166Ho and chitosan,166Ho-chitosan complex was developed for treatment of tumors such as hepatocellular carcinoma. This complex has been lately prepared with high radiochemical purity in our lab. The preclinical studies of the complex however should be performed to evaluate the tracer concentration in target and normal tissues before human use. Methods: In this study,166Ho-chitosan was prepared and its preclinical studies for treatment of hepatocellular carcinoma was carried out by injection of the radiopharmaceutical into the rabbit's liver via two different methods, surgery and venography. Leakage of the injected activity from the injection site in the rabbit organs was investigated using SPECT and SPECT-CT imaging up to 24 hours. Results: Both SPECT and SPECT-CT imaging of the rabbits showed that there was no significant leakage of the injected activity. Almost all the activity would remain in the injection site at least 24 h post injection. Conclusion: Considering all of the excellent features of the complex, this radiopharmaceutical is suggestive for treatment of hepatocellular carcinoma by radioembolization method

Preparation and quality control of lutetium-177 bleomycin as a possible therapeutic agent

Due to interesting therapeutic properties of 177Lu and antineoblastic antibiotic, bleomycin (BLM), 177Lu-bleomycin (177Lu-BLM) was developed as a possible therapeutic compound. Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of a natural Lu2O3 sample with a thermal neutron flux of 4 × 1013 nźcm-2źs-1. The product was converted into chloride form which was further used for labeling of BLM. In optimized conditions a radiochemical purity of 98% was obtained for 177Lu-BLM shown by instant thin-layer chromatography (ITLC) (specific activity, 740 GBq/mmole). Biodistribution studies of Lu-177 chloride and 177Lu-BLM were performed in wild-type rats. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a pattern similar to the other radiolabeled bleomycins. Lu-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models

Development of 153Sm-DTPA-rituximab for radioimmunotherapy

Combining beta-particle effect with therapeutic properties of anti-CD20 monoclonal antibody in lymphomas, Mabthera™ (rituximab) was targeted in this study. The antibody was labeled with 153Sm-samarium chloride (185 MBq) after conjugation with freshly prepared ccDTPA. Conjugated-rituximab was obtained by the addition of 1 ml of a rituximab pharmaceutical solution (5 mg/ml, in phosphate buffer, pH = 7.8) to a glass tube precoated with freshly prepared ccDTPA (0.01–0.1 mg) at 25 degrees centigrade. Sm-153 chloride was obtained by a thermal neutron flux (5 × 1013 nźcm–2źs–1) of an enriched 152Sm2O3 sample, dissolved in acidic media. Radiolabeling was performed in one hour by the addition of DTPA-rituximab conjugate at room temperature. Radiochemical purity of 96% (ITLC) and 98% (HPLC) were obtained for the final radioimmunoconjugate (specific activity = 120 TBq/mmol). The final isotonic 153Sm-rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies in normal rats were performed to determine radioimmunoconjugate distribution up to 24 h. SPECT images were also obtained using 103 keV photons up to 48 h

Preparation, quality control and biodistribution studies of 165Dy-chitosan for radiosynovectomy

The preparation of 165Dy-labeled chitosan for radiosynovectomy applications is described in this paper. 165Dy (T1/2 = 2.33 h) was prepared by irradiation of natural Dy(NO3)3 at a flux of 3.4 x 1013 neutrons/cm2.s for about 6 h. The irradiation resulted in the production of 11.1 GBq (300 mCi) of 165Dy activity. Emitting gamma ray (94.7 keV) and beta particles (Emax = 1.3 MeV, 83%) 165Dy decays to 165Ho. Eight hours after bombardment, the corresponding specific activity was 703 MBq/mg (19 mCi/mg). The irradiated target was dissolved in 0.1 N HCl solution. Radionuclidic purity was ascertained by high resolution gamma spectrometry. Chitosan solution was prepared in acetic acid solution (pH 3). The chitosan solution was labeled with 165Dy to prepare 165Dy-chitosan (165Dy-Chit) complex (labeling yield, greater than 99% and specific activity small tilde 3.7 TBq/mmol). In optimized conditions (pH 3, 35 mg/4 ml chitosan acidic solution, and 370 MBq of 165Dy) Chit was stable after 48 h. Bioevaluation of the prepared 165Dy-Chit was carried out by injecting 37 MBq (1 mCi, 50.100 mi1) directly into the knee joints of wild rats. Free 165Dy cation was also injected to study the effect of complex formation on the retention of radionuclide in the administered site. To study the consequence of radioactivity leakage from the administration site, a dilute sample of the complex was injected intravenously into the rats followed by biodistribution studies. It was observed that there was no significant extra-articular leakage of the injected activity over the study period of 24 h post-injection