Preparation and quality control of 153Sm-[tris[1, 10 -phenanthroline] samarium [III]] complex

The 153Sm-[tris[1, 10-phenanthroline] Samarium[III]]complex [153Sm-PL3] was prepared in view of development of targeting therapeutic compounds for malignancies, and interesting in-vitro anti-tumor activities of lanthanide phenanthroline complexes,. Sm-153 chloride was obtained by thermal neutron flux [4 × 1013 n.cm- 2.s-1] of enriched 152Sm2O3 sample, dissolved in acidic media. The labeling was performed in ethanol in 24h, controlled by ITLC [1.0mM DTPA, pH.5, as mobile phase]. The partition coefficient for the labeled compound was also determined. Results: A radiochemical yield of more than 95% was obtained. Radiochemical purity of 96% was obtained using ITLC with specific activity of about 27.75 GBq/mg. The radio-labeled complex was stable in aqueous solution at least 24 hours and no significant amount of free 153Sm was released from the complex. The partition coefficient for the labeled compound was determined [log P. 3.4]. The complex was stable in final formulation for 66h. The biological evaluation of the compound is under investigation. The radiolabeled compound used in this study was a very inexpensive and useful agent for the use as a therapeutic compound

Direct technetium radiopharmaceuticals production using a 30MeV Cyclotron

Technetium-99m is the major radionuclide used in the world and mainly is provided by fission product. However extensive research has been conducted on the use of accelerators for production of [99m]Tc. This investigation reports the production of [99m]Tc radioisotope using cyclotrons followed by the preparation, quality control and biodistribution studies of four major Tc-radiopharmaceuticals. The high purity molybdenum natural target [130mg/cm[2]] was irradiated in a Cyclone 30 accelerator using 160 microA of 25 MeV proton beam energy for 1000 microA-h. After dissolution, the technetium radionuclides were extracted using methyl ethyl ketone [MEK] followed by preparation of Tc-MIBI, Tc-DTPA, Tc-DMSA and Tc-phytate as radiopharmaceutical samples. The results of quality controls and animal biodistribution studies showed successful production of Tc radionuclides [including [99m]Tc] in the bombarded target and subsequent labelling of the kit with Tc. The developed high power Mo target if constructed using enriched [100]Mo, could be a practical method for large-scale production of [99m]Tc and promising as an alternative to fission product [99m]Mo- [99m]Tc generators for local applications near cyclotron facilities

Preparation and quality control of radiolabeled streptokinase for thrombosis imaging

In order to diagnose the site of thrombi, radiolabeled streptokinase can be prepared. The radiolabeled compound can be used in imaging of thrombi in many cardiovascular diseases. Streptokinase was successively labeled with [[67] Ga]-gallium chloride using cyclic DTPA-dianhydride. The conjugation with DTPA was optimized for concentration, time and temperature followed by size exclusion chromatography using G-50 Sephadex. The radiochemical purity of the tracer was checked using HPLC and ITLC methods. The biodistribution studies were performed in normal rats up to 167 h using tissue counting and preliminary SPECT studies up to 2h. The radiolabeled enzyme was prepared in 60 minutes after incubation at room temperature, with the radiochemical purity of >95% [HPLC] and >99% [ITLC] methods. The radioactivity was accumulated in lung, intestine and liver as shown by scarification and SPECT [Single Photon Emission Computer Tomography] methods. Radiolabeled Streptokinase was prepared in suitable radiochemical purity and its biodistribution is comparable to other radiolabeled proteins. Further studies are required to investigate the imaging properties of the tracer in appropriate animal mode

Preparation and biodistribution of [67Ga]-labeledoxytocin for SPECT purposes

Oxytocin [OT] is a paracrine hormone with various biological activities and many sex organs in both sexes, as well as many tumor cells have shown to have related receptors. In this study the development of a receptor imaging tracer for possible tumor imaging has been described. OT was successively labeled with [67Ga]-gallium chloride after conjugation with freshly prepared cyclic DTPA-dianhydride. The best results of the conjugation were obtained by the addition of 1 ml of a OT pharmaceutical solution [2 mg/ml, in phosphate buffer, pH=8] to a glass tube pre-coated with DTPA-dianhydride [0.02 mg] at 25°C with continuous mild stirring for 30 min. Radiochemical purity [RCP] of the labeled compound was determined, using RTLC and ITLC followed by stability tests and animal biodistribution studies. Radiolabeling took about 60 minutes with a RCP higher than 98% at optimized conditions [specific activity = 1000 Ci/mM, labeling efficiency 80%]. The stability of the tracer at room temperature was significant, up to an hour. Preliminary in vivo studies in normal female rat model showed ovary/blood and ovary/muscle ratio uptake of the tracer in 60 minutes to be 4.53 and 9.18, respectively. The result was consistent with the reported OT receptor distribution in normal female mammals. The radiolabeled oxytocin, prepared in this study, was a possible fast acting tracer for OT receptor imaging; studies however, more studies are required to determine the best imaging conditions especially in larger mammal animals

Development of [201T1][III] oxinate complex for in vitro cell labeling

The incorporation of thallium-201 into 8-hydroxyquinoline was targeted for cell labeling due to interesting physical properties and wide availability of this nuclide as a single photon emission computed tomography [SPECT] radionuclide. Thallium-201 [T[1/2]=3.04 d] in Tl[+] form was converted to Tl[3+] cation in presence of O[3]/6M HCl and di-isopropyl ether, controlled by radiothin layer chromatography [RTLC] /gel electrophoresis methods. The final evaporated activity reacted with ethanolic 8-hydroxy-quinoline [oxine] solution in normal saline to yield [[201]Tl][III] oxinate at room temperature after 0.5 h, followed by solid phase extraction/purification using C18 Sep-Pak column and partition coefficient determination for water/lipid solubility. In vitro red blood cell [RBC] labeling was also performed. A radiochemical yield of more than 95% was obtained. Radiochemical purity of 92% was obtained using RTLC [>90% using HPLC] with specific activity of about 820 GBq/mmol. The tracer was stable in the final product and in presence of human serum at 37°C up to 6h. The partition coefficient of lopP=5.5 was obtained. The labeled compound was used in RBC labeling. The cell uptake ratio was 0.47 after 240 min. [[201]Tl][III] oxinate used in this study is a widely available agent for use in RBC labeling studies in biology, medicine and various other research areas

Radiosynthesis of [[103]Pd]-di-actyl-bis [N[4]-methylthio-semicarbazone]: a potential therapeutic agent

Due to interesting tumor imaging properties of bis-thiosemicarbazones, [[103]Pd]-di-acetylbis [N[4]-methylthiosemicarbazone] [[[103]Pd] ATSM[2]] was prepared according to the analogy of radio copper homologues. Palladium- 103 [T[1/2]=16.96 d] was produced via the [103]Rh [p,n] [103]Pd nuclear reaction with proton energy 18 MeV. The final activity was eluted in form of Pd [NH[4]][2]Cl[2] in order to react with bis-thiosemicarbazones to yield [[103]Pd]- labeled compounds. Chemical purity of the final product was confirmed to be below the accepted limits by polarography. The labeled compound was purified by reverse phase column chromatography using C[18] plus Sep-Pak. The partition co-efficient of the final complex was determined. The initial physico-chemical properties of the labeled compound was compared to those of their copper homologues.: Radiochemical purity of more than 99% using RTLC was obtained [specific activity of about 12500-13000 Ci/mol]. The stability of the tracer was checked in final product and human serum, at 37[degree sing] C up to 48h. The labeled compound prepared in this study is probably one of the few new [103]Pd-radiolabeled compounds which have a potential for future biological studies, regarding its suitable physicochemical stability

[Experimental production and initial imaging of [18 F]-14-Fluoro-6-thia-hepatadecanoic acid [[18F]-FTHA] for myocardial performance]

[18F]-6-thia-14-fluoro-heptadecanoic acid 3b, a free fatty acid, has been used in myocardial PET imaging. In order to establish an automated synthesis module for routine production in the country, a study performed for optimization of the production conditions as well as making modifications. [18F] Benzyl-14-Fluoro-6-thia-heptadecanoate 2b was prepared in no-carrier-added [n.c.a] form from C in Benzyl-14-tosyloxy-6-thia-heptadecanoate 1 in one step at 90 Kryptofix2.2.2/[18F] and acetonitrile as the solvent followed by Silica column chromatography. The radiolabeled ester 2 was then hydrolyzed to yield [18F]-6-thia-14-fluoro-heptadecanoic 3b. The final solution was concentrated using C18 SPE system and administered to normal rats for biodistribution as well as co-incidence imaging studies. The synthesis took 15 min with overall radiochemical yield of 15-25% [EOS] and chemical-radiochemical purity more than 94%. Automation was performed using a two-pot synthesis. The best imaging time was shown to be 140-180 minutes post injection. Using this procedure a fast, reliable, automated synthesis for the cordial PET tracer, i.e. [18F]-FTHA can be obtained without HPLC purification step

Tissue uptakes of 67Ga-bleomycin and carrier free 67Ga in fibrosarcoma - bearing mice

67Gallium-bleomycin complex [67Ga-BLM] was prepared using Thakour method. Radio-thin-layer-chromatography of prepared complex showed A2 and B2 radiopeaks with Rf at 0.7 and 0.4 respectively with a purity of above% 95. Tissue uptake of 67Ga-BLM and 67GaCl3 in twelve tissues including tumor, blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content,bladder and the total body were counted by well counter at 1, 2, 4, 24 and 48 hours post injection of radiopharmaceuticals. Uptakes of tissues are expressed as percent injected dose per gram of tissue. The clearance rate of 67Ga-BLM was 1.75-1.95 times faster than 67GaCl3 at all time intervals. Bladder uptakes of 67Ga-BLM were highest among twelve tissues at 1,2 and 4 hours after injection, then falling rapidly after 24 and 48 hours. Blood uptake of 67Ga-BLM was lower than 67GaCl3 in all time intervals. Colon content uptake of 67Ga-BLM was highest among twelve tissues at 2 and 4 hours post injection. Tumor to tissue activity ratios were also calculated, showing an increase of tumor to blood and muscle ratios. Tumor to blood ratio increased from 0.3 at 1 hour to 5.3 at 48 hours. Activity ratio of muscle increased from 0.5 at 1 hour to 5.5 at 48 hours. Whole body counting of animals showed that effective half lives of 67Ga-BLM and 67GaCl3 were about 1 and 15 hours respectively, which renders faster excretion of 67Ga-BLM complex. Biodistribution data clearly indicates that prepared complex in comparison with carrier free 67Ga [67GaCl3] has two main advantages: 1] high tumor to soft tissue uptake ratio that make it suitable for tumor imaging, 2] faster excretion specially at first three hours post injection. In addition complex is stable in vitro and in vivo

Preparation, distribution, stability and tumor imaging properties of [62 Zn] bleomycin complex in normal and tumor - bearing mice

Bleomycin [BLM] has been labeled with radioisotopes and widely used in therapy and diagnosis. In this study BLM was labeled with [62Zn] zinc chloride for oncologic PET studies. The complex was obtained at the pH=2 in normal saline at 90°C in 60 min. Radio-TLC showed an overall radiochemical yield of 95-97% [radiochemical purity > 97%]. Stability of complex was checked in vitro in mice and human plasma/urine. Preliminary in vivo studies performed to determine complex stability and distribution of [62Zn] BLM in normal and fibrosarcoma-bearing mice. [62Zn] BLM accumulated significantly in induced fibrosarcoma tumors in mice according to bio-distribution/imaging studies. [62Zn] BLM can be used in PET oncology studies due to its suitable physico-chemical properties as a diagnostic complex in vitro and in vivo. Further studies should be performed for evaluation of the complex behavior in higher animals

[66Ga] oxine complex; preparation and stability as a possible PET radiopharmaceutical

Gallium-66 [T1/2= 9.49 h] is an interesting radionuclide that has potential for positron emission tomography [PET] imaging of biological processes in intermediate to slow target tissue uptake. Oxine has been labeled with this radioisotope in the form of [66Ga]gallium chloride for its possible diagnostic properties. Materials and methods: 66Ga was produced in the 30 MeV cyclotron [Cyclon-30, IBA] via the 66Zn[p,n]66Ga reaction.TLC was performed on polymer backed silica gel. A Gamma spectrometer HPGe detector was used for countings. After the bombardment, the production yield was 11.2 mCi/ m Ah. The [66Ga]Oxine complex was obtained at the pH=5 in phosphate buffer medium at 37°C in 10 minutes. Radio-TLC showed an overall radiochemical yield of 97% [radiochemical purity > 98%]. The chemical stability of the complex was checked in vitro with a specific activity of 896 mCi/ml. [66Ga]oxine can be used in diagnostic studies due to its suitable physico-chemical properties both in vitro and in vivo