[en] A facility for the production of ⁹⁹Mo-^99mTc generators (GPL) in clean room system was provided by the IAEA under Technical Cooperation Project. Regular production of Pakgen ^99mTc generators has been started from January 2003. The GPL is provided with A, C and D categories of clean room specifications and various materials used for generator preparation are transferred through airlocks while dress change rooms are provided for personnel. More than 1800 Pakgen ^99mTc generators with calibrated activities (five days reference date) ranging from 300 to 600 mCi of ⁹⁹Mo have been supplied to various nuclear medical centres in Pakistan. Before preparation, the generator bodies and various sections of GPL have been cleaned and disinfected. During the preparation, required calculated activity of ⁹⁹Mo has been loaded on the columns of pre assembled generators by prewash, loading and postwash steps and quality of the generator has been checked by elution efficiency and molybdenum breakthrough of eluate obtained after an hour from postwash step by comparing the measured activity with the theoretical activities. All these calculations have been carried out using computer programme MOGEN-I developed in Visual Basic 6 software; this software is suitable for recording and acquitting commercial data, monitoring production and quality control. Mathematical equations for theoretical calculation of generator parameters using ⁹⁹Mo-^99mTc-⁹⁹Tc decay schemes have been used in this software; otherwise these calculations are laborious and time consuming. During the elution, theoretical prediction of the performance of a ⁹⁹Mo-^99mTc generator, in terms of the activity of ⁹⁹Mo, ^99mTc on the column, activity of ^99mTc in the generator eluate, the generator elution efficiency and the total mass of technetium (^99mTc + ⁹⁹Tc ) present in a given eluate, have been carried using another software MOGEN-II. The input variables are ⁹⁹Mo activity, generator elution efficiency, number of elutions, the growth time between elutions, the decay time between elution and the use of ^99mTc. The output of the program for each elution gives the activities of ⁹⁹Mo and ^99mTc, atom numbers of ⁹⁹Mo, ^99mTc and ⁹⁹Tc and the ⁹⁹Tc/^99mTc atom ratio for the generator immediately before elution, for fresh eluate, for decayed eluate and for the generator after elution. This software will be useful for judging the quality of Pakgen ^99mTc generators for a week or so. Pakgen ^99mTc generator provides, by elution, ^99mTc-sodium pertechnetate in sterile, isotonic solution ready for intravenous or oral administration or for aseptic preparation of ^99mTc labelled radiopharmaceuticals. All Pakgen ^99mTc generators are test eluted before shipment. Quality tests performed are elution efficiency, molybdenum breakthrough, radiochemical purity, chemical purity, radionuclidic purity, sterility and apyrogenicity. The eluate fulfils the quality control criteria prescribed by International Atomic Energy Agency and various Pharmacopoeias like United States, British and European for sodium pertechnetate ^99mTc injection. In hospitals, the Pakgen ^99mTc generators showed optimum performance in terms of elution yields, molybdenum breakthrough, labelling yields and quality of gamma scans

[en] Radiolabelled dimercaptosuccinic acid (DMSA) has been utilised by several investigators as a safe and effective renal radiopharmaceutical for static 'imaging'. A review of the available literature indicates that Tc-99-DMSA is the best agent to study the renal anatomy. DMSA being very reactive, needs extra care, slight mishandling results in the change of target organ. To overcome this problem we prepared a kit which showed improved results as there was no uptake in any other viscera, and has been found to be comparable wit commercially supplied kit. (author)

[en] The aim of the present study is to formulate a lyophilized single component kit of N-N-Ethyleno-I-dicysteine (EC) to be labeled with /sup 99m/Tc. It has following features, (a) easy to prepare (b) can be used as an effective alternative to radioiodine labeled orthoiodohippurate a ^physiological gold standard^. For this, effect of various parameters like pH, reducing agent, stabilizer and additives have been studied in details and finally optimum conditions have been established to formulate a single component kit having the above characteristics, This final kit formulated at pH 10 has a labeling efficiency of > 98.5%. Although the evaluation of biokinetic data in animals showed favored parameters at various pH levels studied by /sup 99m/Tc-EC at pH 10 was found to be most suitable for human use. 9 normal volunteers (2 F and 7M) were included in the study. Dynamic scintigraphy was carried out with /sup 99m/Tc-Ec (pH 8) in 3 volunteers (6 kidneys), at pH 10 in 6 volunteers (12 Kidneys) and compared with /sup 99m/Tc-Mag/sub 3/. Background ratio, renograms, relative renal functions and, semi quantitative parameters were investigated in all the studied. The background ratios (mean -+SD) at 30th minute were 0.229 -+0.000 and 0.236-+0.018 for 99m Tc-EC at pH 10 and /sup 99m/Tc-MAG respectively. The mean -+sem values of T/sub max/ and T/sub 1/2/ for /sub 99m/Tc(pH 10) were 3.7 -+0.6 and 7.3 -+1.0 respectively, while for /sup 99m/Tc-MAG/sub 3/ they were 4.0 -+0.8 and 7.9 - +1.4 with p values 0.001 and 0.049 respectively. The values of RRF for /sup 99m/Tc-Ec and /sup 99m/Tc-MAG/sub 3/ were 50.8 -+3.11 and 51.2 -+ 3.4 respectively with o value of 0.822, the residual activity at 25th minute (A/sub 25//A/sub MAX/ ) and renal uptake were 0.209 -+ 0.007 and 12.67 -+ 2.80 for /sup 99m/Tc-EC and 0.218 -+ 0.035 and 10.53 -+ 2.98 for /sup 99m/Tc-MAG/sub 3/ (P=0.007 and 0.0003) respectively. The correlation coefficients (R/sup 2/ for T/sub MAX/, T/sub 1/2/, A/sub 25/A/sub MAX/ and renal uptake were 0.96, 0.69, 0.93 and 0.85 respectively. The single vial kit formulated at pH 10 is simple to prepare and low at cost as compared to commercially available two or three component EC kit MAG/sub 3/. It does not accumulate in liver as in case of MAG/sub 3/. (author)

[en] The lyophilized MIBI kit was dissolved in 1 ml sterile saline or 250 μg/ml ascorbic acid and dispensed into 0.2 ml fractions, which were stored at -20 deg C for 12 days. The solution was prepared by using two different protection methods. In the first method evacuated vials were used for storage of fractionated solution while in the second method an antioxidant agent, ascorbic acid was employed. The radiochemical impurity of ^99mTc-MIBI in the unprotected fractions rises with time. Exclusion of air as well addition of ascorbic acid in fractionated solutions gave very good results. The labeling efficiency and biodistribution of fractionated solutions was the same as the lyophilized kit even after 12 days. (author)

[en] Somatostatin (SS) plays a major role in the physiological regulation of hormones and organs. Radiolabelled somatostatin analogues have been studied for targeted radiotherapy of neuroendocrine tumors and with other malignancies known to bear somatostatin receptor, such as lymphoma, breast cancer, small-cell lung cancer and melanoma. Reactor produced ¹⁷⁷Lu is emerging as an important radionuclide for cancer therapy since it decays with half-life of 6.71d by the emission of β^- particles with E_β of 498 keV (78.6), 384 keV (9.1%) and 176 keV (12.2) to stable ¹⁷⁷Hf. The ¹⁷⁷Lu radionuclide has tissue mean range of 670 μm is considered to be more effective for the treatment of small tumour. High specific activity ¹⁷⁷Lu radionuclide (> 8Ci/mg) prepared in our laboratory is considered to be appropriate for labelling peptides. Several experiments for obtaining optimum labelling yield of ¹⁷⁷Lu-DOTA-Tyr3-Octreotate under different reaction parameters such pH, incubation time and reaction temperature were performed. Radiochemical purity of ¹⁷⁷Lu-DOTA-Tyr3- Octreotate was determined by radio-TLC with C18 plates developed in 70:30 MeOH:10% NH₄OAc. Under these conditions ¹⁷⁷Lu-DOTA-Tyr3-Octreotate appears at Rf 0.8 while ¹⁷⁷Lu-acetate stays at the R_f 0. High labelling yield (>98%) of 177Lu-DOTA-Tyr3-Octreotate was obtained at pH 4.5 at a temperature of 90 deg. C for 30 minutes incubation time. The ¹⁷⁷Lu-DOTA-Tyr3-Octreotate was further investigated for stability in acetate/ascorbate buffer and saline at room temperature (12.15 deg. C). The data showed that the labelled complex was stable in buffer and saline medium for a period >24 hours. Animal study of ¹⁷⁷Lu-DOTA-Tyr3-Octreotate was performed in ∼200 g male Sprague Dawley rats. Two hundred microlitres of the labelled (80 μCi) were injected into the tail veins of rats and each rat was killed at 1 hour, 2 hours, 6 hours, 12 hours, 24 hours and 72 hours. Countings were performed using Capintec dose calibrator. The biodistribution study of ¹⁷⁷Lu- DOTA-Tyr3-Octreotate in rats indicates that the critical organ was the pancreas and the excretion route was through kidney. All the rats during the study were found to show normal behaviour (movement, sleeping, eating). For Internalization studies, AR42J cells were plated to a final concentration of 1x10⁶ cells into 35 mm culture dishes and incubated for 1 h at 37 deg. C. Cells (1x10⁶ cells/tube) were incubated with 1x10⁴ cpm /tube of ¹⁷⁷Lu-DOTA-Tyr3-octreotate for 5, 20, 40, 80, 120 minutes at 37 deg. C. Incubation was interrupted by removal of the medium and % internalized radioactivity was calculated. At the same time non specific binding (NBS) was evaluated by incubation of cells with tracer in the presence of a high concentration of unlabelled DOTA-TATE (150 μL of 10 μmol in each tube). The ¹⁷⁷Lu-DOTA-Tyr3-octreotate showed more than 6% internalisation into AR42J cells after 80 minutes

[en] A facility for the production of ⁹⁹Mo-^99mTc generators, along with a clean room system was established at PINSTECH by the IAEA under a technical cooperation project (PAK/4/04) with finance of US $200 000. This generator production facility comprises three clean rooms: (i) preparatory room (grade D), (ii) generator loading room (grade C), and (iii) quality control room (grade B). The materials used for generator preparation are transferred through airlocks while dress change rooms are provided for personnel entry. Two hot cells equipped with in-cell equipment are installed in a generator production room. The prepared generators are transferred via conveyor belt to the quality control room for measuring elution efficiency and ⁹⁹Mo breakthrough. Regular production of Pakgen ^99mTc generators started in January 2003. More than 1900 Pakgen ^99mTc generators with calibrated activities (five days reference date) ranging from 300 to 600 mCi of ⁹⁹Mo have been supplied to various nuclear medical centres in Pakistan. Before preparation, the generator bodies and the various sections of the Generator Production Laboratory are cleaned and disinfected. During preparation, the required calculated activity of ⁹⁹Mo is loaded on the columns of preassembled generators by pre-wash, loading and post-wash steps and the quality of the generator is checked by elution efficiency and molybdenum breakthrough of eluate obtained after one hour of the post-wash step. All these calculations are carried out using the MOGEN-I computer program developed in Visual Basic 6 software. This software is suitable for recording and acquitting commercial data and monitoring production and quality control. All Pakgen ^99mTc generators are test eluted before shipment. Quality tests performed include: elution efficiency, molybdenum breakthrough, radiochemical purity, chemical purity, radionuclidic purity, sterility and apyrogenicity. The eluate fulfils the quality control criteria prescribed by the IAEA and the European Pharmacopoeia. In hospitals, the Pakgen ^99mTc generators showed optimum performance in terms of elution yields, molybdenum breakthrough, labelling yields and quality of gamma scans. (author)

[en] Technetium-99m radionuclide is the workhorse of nuclear medicine and currently accounts for over 80% of all in-vivo diagnostic procedures. Technetium, element 43 in the Periodic Table does not occur naturally but was discovered in 1937 by Perrier and Segre. The daughter radionuclide technetium-99m (/sup 99m/Tc, T/sub 1/2/ = 6 h) is formed from the decay of parent molybdenum-99 (/sup 99/Mo, T/sub 1/2/ = 66 h). The prominent position of /sup 99m/Tc on the market has been due to its near ideal nuclear properties, the ready availability in the form of convenient /sup 99/Mo. /sup 99m/Tc generator system and the rapid progress made in recent years in the development of variety of /99m/Tc radiopharmaceuticals for applications in oncology, cardiology and other fields. The /sup 99/Mo radionuclide is produced by the fission of uranium with thermal or fast neutrons in the nuclear reactor. The separation of /sup 99m/Tc from /sup 99/Mo is based on the chromatographic alumina column where the carrier-free daughter /sup 99m/TcC/sub 4/ formed from /sup 99/Mo by beta-decay is eluted periodically by 0.9% saline while the molybdate remains adsorbed on the alumina column. Examination of the /sup 99/Mo-/sup 99m/Tc-/sup 99/decay scheme leads to mathematical equations for theoretical calculation of generator parameters in order to judge the performance of /sup 99/Mo-/sup 99/Tc generator. However, these calculations are laborious and time consuming. A computer program 'MOGEN-TEC-2' for the calculation of /sup 99/Mo-/sup 99/Tc generator parameters using Java 1.3 software which has the advantage of working under different operating systems, has been developed. Here the data of input variables is taken in text area and Output, for each elution after execution of the program, is displayed in Label area. The input variables are /sup 99/Mo activity, generator elution efficiency, number of elution, the growth time between elution, the decay time between elution and the use of /sup/99m/Tc. The output of the program for each elution gives the activities of /99/Mo and /99m/Tc, atom numbers of /sup 99/Mo, /sup 99m/Tc and /sup 99m/Tc and the /sup 99/Tc//sup 99/Tc atom ratio for the generator immediately before elution, for fresh eluate, for decayed eluate and for the generator after elution. The software is being used comfortably and accurately. (author)

[en] Objective:This study was aimed at the evaluation of EB1 as an inflammation-imaging agent in animal models after ascertaining its normal biodistribution. Methods: Kit was formulated by adding SnC12 as reducing agent in EB 1 compound. EDTA was used as chelating agent. Buffer was added to lower the pH of solution to 5. Freeze dried kits were prepared for later use in experiments. Kits were reconstituted with 0.5 ml of fresh eluate of 99m-TcO4 containing total activity of about 370 MBq. Radiochemical quality control was checked by conventional strip method using double solvent technique.Biodistribution was assessed in 15 Sprague Dawley rats. An injection of 10 MBq was given in tail vein in each animal. Animals were killed at pre-specified time intervals; organs were separated, weighed and counted. Counts recovered were corrected for decay. Inflammation models were prepared by injecting turpentine oil in the thigh muscles of 14 rabbits. In one rabbit inflammation was not induced and was used as control for EB 1. In 3 of inflammation models plain 99m-TcO4 was injected (control II). In another group of 3 animals 99m-TC-EDTA was injected (control II). In the last group of 8 animals 99m-TcO4-EB 1 was injected (experimental gp). Animals were serially imaged under Seimens' E-Cam gamma camera for the distribution of activity in different organs and at the site of inflammation. Results: Kit labeling efficiency was 90.5 + 2.5% with 2.5 + 0.8% free activity and 7 + 1.1% hydrolyzed form. Animal study on rats showed that pharmaceutical is mainly excreted by kidneys (51.57 + 9.2% at 15 minutes and 81.73 + 7.9% at 4 hours). Uptake in liver was 7.52 + 2.2% at 15 minutes that decreased to 2.3 + 0.5% at 4 hours. Activity in intestine increased from 5.48 + 2.9% to 7.05 + 1.6% at 15 minutes to 4 hours. Activity in background (=blood) decreased from 0.13% (at 15 minutes) to 0.04% at 4 hrs. In bones EB1 uptake decreased from 0.68% to 0.15% at 15 minutes to 4 hours. In inflammation models uptake of 99m-Tc-EB 1, target to non-target ratio (TNT) was 2.06+ 0.46, 2.10+0.48, 2.06+0.51, 2.06+0.46, at 30 minutes, 60 minutes, 120 minutes and 180 minutes. Uptake of plain 99m-TcO4 (TNT) was 1.88 + 0.16, 1.70 + 0.38, 1.67+0.32 and that of 99m-Tc-EDTA was 1.97 + 0.4, 1.80 + 0.47, 1.63 + 0.18, 1.45 + 0.18 at 30 minutes, 60 minutes, 120 minutes and 180 minutes. Conclusion: Kit formulation for 99m-Tc labeled EB1 gives high labeling yield with favorable properties for imaging of inflammation. Its uptake at the site of inflammation is stable for' up to 3 hrs post injection and is considerably high compared with plain 99m-TcO4 and EDTA. Considering short half-life of 99m-Tc, imaging can be done at any time between 30 minutes to 3 hours post-injection. (authors)

[en] There is no recognized 'gold standard' for imaging sites of infection or inflammation. Many technetium complexes have been put forward as being efficacious in the detection of inflammation and infection. Synthesis of ^99mTc-Kanamycin and ^99mTc-Isoniazid was investigated and evaluated as infection imaging agents in animal models. The direct method of labeling of Kanamycin and Isoniazid with technetium-99m was exploited which is simple, rapid, efficient and does not require bifunctional chelating agents. Kanamycin is an anti-infective used for treatment of infections when penicillin or other less toxic drugs cannot be used. Kanamycin was labeled with technetium-99m pertechnetate using SnCl₂ · 2H₂O as reducing agent. Labeling efficiency and radiochemical purity and stability were assessed by a combination of ascending paper chromatography and instant thin layer chromatography on silica gel. The labeling efficiency depends on ligand / reductant ratio, pH, and volume of reaction mixture. At low pH (2-5) the minimum labeling efficiency is 75, while at pH 6-7 the labeling efficiency of ^99mTc-Kanamycin is > 97%. In basic media at pH 8 the labeling efficiency is decreased (60-72%). The complexation of ^99mTc with Kanamycin is not rapid and maximum labeling efficiency is achieved after 30 minutes. The resulting complex of ^99mTc-Kanamycin is quite stable and labeling efficiency of ≥ 98% is maintained for up to 6 h. The final formulation for the radiotracer ^99mTc-Kanamycin was: Kanamycin 4mg; SnCl₂ 2H₂O 20 μg; pH 6-7; ^99mTc 370-500 MBq; reaction mixture volume ∼2 ml; and incubation time 30 min at room temperature. In vitro binding of ^99mTc-Kanamycin to S. Aureus bacteria were assessed by the method described Welling, et al. For comparison purposes binding of ^99mTc-Ciprofloxacin to bacteria were also performed. In vitro binding of ^99mTc-Kanamycin to bacteria was in the range of 40-50%, while binding of ^99mTc-Ciprofloxacin ranged from 40 to 65% (n=4). Biodistribution studies of ^99mTc-Kanamycin were performed in rats/rabbits. Saline (0.3 ml) containing 2x10⁸ cfu viable S. aureus ATCC 25923 was injected into the right thigh muscle of each animal followed by scintigraphy after 48 h, when significant swelling was visible at the injection site. A significantly higher accumulation of ^99mTc-Kanamycin was seen at sites of S. aureus infected animals (rat/rabbit). The antitubercular drug Isoniazid has also been labeled with ^99mTc for use as a specific radiopharmaceutical in the early and correct diagnosis of tuberculosis. The maximum radiolabeling yield 95% was obtained with reaction mixture containing 2 mg Isoniazid; SnCl₂ · 2H₂O 100 μg; pH ∼7; ^99mTc 370-500 MBq; and reaction mixture volume ∼2 ml. The reaction mixture was incubated for 25 min in a boiling water bath. Scintigraphy in animals was carried out after intravenous administration of ^99mTc-Isoniazid in the dorsal ear of rabbits. Imaging was performed at different time intervals after administration till 24 h. ^99mTc-Isoniazid is able to concentrate specifically and irreversibly in vivo bacterial model in rabbit tubercular infection. The uptake of directly labeled ^99mTc- Isoniazid in tubercular lesion is comparable to indirectly labeled ^99mTc-Isoniazid

[en] Full text: In a quest for more effective radiopharmaceutical for palliation of pain experienced by metastatic cancer patients, this study relates the results obtained with therapeutic beta emitter radionuclides of Samarium-153, Holmium-166, Yttrium-90 and Lutetium-177 complexed to bone seeking phosphonate ligand of ethylenediamine tetramethylene phosphonic acid (EDTMP). The objective of this study is to formulate and evaluate Samarium-153, Holmium-166, Yttrium-90 and Lutetium-177 labeled EDTMP for bone pain palliation and to compare them with ¹⁵³Sm-EDTMP that is currently being used in many centers of the world. All the radionuclides were prepared by n,a-tilde reaction. Quality control was checked by paper chromatography and paper electrophoresis. Various parameters were optimized to formulate these radiopharmaceuticals with maximum labeling efficiency. Sprague-Dawley male rats were used for biodistribution and imaging study. The labeling efficiency of ¹⁵³Sm-EDTMP was found to be > 99% at pH 7.5 with 1:5 (Sm: EDTMP) molar ratio incubated for 20 minutes at room temperature. For ⁹⁰Y-EDTMP the labeling efficiency was > 95 at pH 7.5 with ligand: molar ratio from 5-12. ¹⁶⁶Ho-EDTMP showed that the complex can be prepared with radiochemical purity of >95% using ligand: molar ratio from 8-12 at pH 7.5. ¹⁷⁷Lu-EDTMP complex showed labeling efficiency >95% using ligand: molar ratio from 20-30 at pH 7.5. During bio-distribution study, skeletal uptake was found to be maximum for ¹⁷⁷Lu-EDTMP (70±2.4%), followed by ¹⁵³Sm-EDTMP (58.5±2.8%), ⁹⁰Y-EDTMP (45±2.1%) and ¹⁶⁶Ho-EDTMP (36±2.1%). All these radiopharmaceuticals showed good renal and rapid blood clearance. The biodistribution study of free radionuclides showed significant uptake of activity by soft tissues including lungs, liver and spleen, with minimal uptake in the skeletal system (¹⁵³SmCl₃ : 7.5±0.04%, ⁹⁰YCl₃: 1.75±0.6%, ¹⁶⁶HoCl₃: 3.3±0.3%, ¹⁷⁷LuCl₃ : 2.5±0.1%). Imaging study carried out for ¹⁵³Sm-EDTMP, ¹⁷⁷Lu-EDTMP and ¹⁶⁶Ho-EDTMP showed good uptake of activity by the skeletal system (including epiphyses, spine and facial bones). Therefore, it was concluded that labeled complexes of these lanthides can be used effectively in the therapy for bone pain palliation, ¹⁷⁷Lu-EDTMP have more potential in this regard. Chlorides of the lanthides cannot be used for bone pain palliation due to their poor skeletal localization. (author)