HPLC investigation of the radiochemical purity of <Superscript>99m</Superscript>Tc-MIBI

Technetium-99m-sestamibi (^99mTc-MIBI) is a small, lipophilic and cationic compound used for myocardial perfusion imaging. In addition, ^99mTc-MIBI has been shown to be useful in identifying several types of tumors, such as breast, lung and thyroid cancers. The high quality of this radiopharmaceutical and its uniformity are very important facts for application of this preparation in clinical practice. The monograph for ^99mTc-MIBI recommends at least 90% radiochemical purity (RCP) for clinical use. Various factors may influence the RCP of certain reagent kits. Some of these include the amount of activity added to the reagent kit, heating time and the age of the formulated kit. The effect of these factors on RCP of ^99mTc-MIBI has been investigated using high performance liquid chromatography (HPLC) and instant thin layer chromatography.     

The effect of selected preparation variables on the radiochemical purity of <Superscript>99m</Superscript>Tc-EDDA-HYNIC-TOC

[^99mTc-EDDA-HYNIC-D-Phe¹, Tyr³]-Ocreotide (^99mTc-EDDA-HYNIC-TOC) increasingly emerges to be an alternative tool for somatostatin receptor (SSTR) scintigraphy of neuroendocrine tumours. The high quality of this radiopharmaceutical and its uniformity are very important facts for application of this preparation in clinical practice. Various factors may influence the radiochemical purity (RCP) of certain reagent kits. Some of these include the amount of activity added to the reagent kit, heating time and the age of the formulated kit. The effect of these factors on RCP of ^99mTc-EDDA-HYNIC-TOC has been investigated using high performance liquid chromatography (HPLC) and instant thin layer chromatography (ITLC).     

Technetium-99m dextran kit: formulation and biological behaviour

A new formulation of stannous-dextran (Sn-Dx) freeze dried kit, containing 60 mg dextran (Dx-70) and 0.08 mg SnCl₂·2H₂O, to be labelled with^99mTc, has been developed. At pH 6.5–7.0. the labelling efficiency was greater than 95%. Gel chromatography column scanning technique was applied for radiochemical purity determination of^99mTc-Dx preparation and the degree of in vivo plasma protein binding. Not less than 70% of the administered activity was bound to plasma and remained constant over a 1h period. The biological behaviour after intravenous injection of^99mTc-Dx kit was characterized by high and efficient yield of the radiopharmaceutical. The preliminarly clinical results on normal subjects showed that the radiopharmaceutical could be a useful agent for scintigraphy of leg lymph vesel, pelvic and inguinal lymph nodes. The activity uptake in liver and kidney (60 min) was relatively very low, whereas the urinal bladder activity (30 min) represents the drainage of the activity entering the blood stream after interdigital injection of^99mTc-Dx.     

Standardization of quality control methods for99mTc radiopharmaceuticals

Physico-chemical characterization of^99mTc-radiopharmaceuticals is presented. Limiting pH values, iso-osmotic pressure and the apparent coefficient values between two immiscible phases are determined too. A selection of radiochromatographic methods /stationary or mobile phase/ for routine quality control of^99mTc radiopharmaceuticals for radiochemical purity was made. The methods chosen are simple, accurate, sufficiently sensitive and fast in operation. The mean values were determined for^99mTc radiopharmaceutical distribution per organs, characteristic for the tested preparates and for radiochemical purity, as well as the time interval from injection to sacrifice of the animals.     

Paper radiochromatography for evaluation of radiochemical purity and stability of [<Superscript>186g</Superscript>Re]Re-HEDP in biological samples after human administration

[^186gRe]Re-HEDP is a radiopharmaceutical used for pain palliation in bone metastases from various primary tumors. The negatron emitter with 〈E _β 〉 = 357 keV ^186gRe is suitable to irradiate cancer and inflammatory cells, but it needs labeling bis-phosphonates as vectors to reach target tissue. Paper radiochromatography was used to evaluate the radiochemical purity of [^186gRe]Re-HEDP in radiopharmaceutical solution as well as in biological samples (serum and urine) from treated patients, in order to follow bone-targeting and excretion. Following the activity concentration in each sample vs. time it is effective to elaborate a bio-kinetic model of the radiopharmaceutical and to optimize administration protocols.     

Kit for instant 99mTc labeling of the antimicrobial peptide ubiquicidin 29-41

Summary The ubiquicidin 29-41 fragment (UBI) is a cationic antimicrobial peptide. The aim of this study was to develop an instant kit formulation for the preparation of ^99mTc-UBI 29-41 in high radiochemical yield and to evaluate its use as an infection imaging agent in humans. The components were selected to produce a direct ^99mTc labeling, presumably to the amine groups of Lys and Arg7. ^99mTc-UBI 29-41 obtained from the lyophilized kit showed radiochemical purity of >97% with an average target/non-target ratio of 2.3±0.6 in positive infection sites at 2 hours. Kits were stable at 4 °C for over 6 months.     

Analytical and radioanalytical quality control of purity and stability of radiopharmaceutical compound [186gRe]Re-HEDP for bone metastases pain palliation

Summary The nuclear properties of ^186gRe make it a useful agent for radionuclide therapy and imaging. The coordination compound [^186gRe]Re-HEDP has proved to be a successful bone seeking agent for palliation of metastatic bone pain. Chemical, radiochemical and radionuclidic purity of commercial radiopharmaceutical [^186gRe]Re-HEDP have been checked by means by γ- and β-spectrometries, INAA and paper radio-chromatography. The results indicate a good radionuclidic purity, with levels of contamination from the short-lived ¹⁸⁸Re well below the required specifications. After injection of the radiopharmaceutical, the radiochemical measurements conducted in vivo, on biological matrices, blood, plasma and urine, have shown that, entering the systemic circulation, ^186gRe dissociates from the bis-phosphonate complex as hydrosoluble [^186gRe]ReO₄-, and the two chemical species follow different biokinetics.     

Radio TLC in quality control and development of radiopharmaceuticals

Radio TLC has been used for determining the radiochemical purity and composition of two^99mTc-radiopharmaceuticals, available as kits and commonly used for diagnostic imaging. Moreover, the same technique has been applied to detect impurities which decrease the specific activity of¹³¹I-derivatized dermatan sulfate, a new potential radiopharmaceutical, and for establishing the best labeling conditions.     

Radiolabeling of EGCG with 125I and its biodistribution in mice

The aim of the present study was to label EGCG with ¹²⁵I and to determine its radiopharmaceutical potential in mice. EGCG was labeled with ¹²⁵I using the iodogen method. The labeling yield and the radiochemical purity of ¹²⁵I–EGCG were determined by radio thin-layer chromatography (RTLC). The Labeling yield was approximately 89.4 %. The radiochemical purity was approximately 96.4 %. The biodistribution studies of the labeled compound (specific activity; 0.47 TBq/μg) were performed in male Kunming mice. The uptakes of ¹²⁵I–EGCG in some organs were determined at different time after injection to the mice. The radioactivity in each organ was counted and the percentage of injected activity per gram of tissue weight (%ID/g) for each organ and blood was calculated. Incorporation of radioactivity in the various tissue/organ was confirmed by microautoradiography. ¹²⁵I–EGCG uptake in the stomach and salivary gland was higher than other organ/tissue. The black silver grains was concentrated in the nucleus, cytoplasm, intercellular substance and capillaries of that various organs, and its unevenly distributed. Thus, ¹²⁵I–EGCG may be radiopharmaceutical for the imaging of the stomach and salivary gland.     

An alkaline kit formulation to obtain [99mTc]MAG3 in high radiochemical yields

An alkaline kit formulation (pH 9) to obtain [^99mTc]MAG₃ with radiochemical puritives over 98% has been developed, avoiding the addition of filtered air to the vial, the use of large amounts of^99mTc activity (i.e., 3.7 GBq) or the reconstitution of large volumes. The use of this radiopharmaceutical in mice showed a minimal accumulation in the hepatobiliary system (0.37±0.3% I.D., 1 h postinjection). However, in rabbits we always obtained good image quality.     

Comparative radiochemical and kinetic study of tumorotropic and renal99mTc-DMSA

A procedure for obtaining a stable^99mTc(V)-DMSA kit and methods for its radiochemical and biological control are described. The effect of pH on radiopharmaceutical stability of the complex was studied. The kinetic parameters of^99mTc(V)-DMSA were determined on rats and compared to the corresponding values for renal^99mTC-DMSA. Clinical tests showed that^99mTc(V)-DMSA is suitable agent for detecting the primary medullar carcinoma of thyroid, as well as for detection of thyroid metastasis.     

Quality control and clinical application of two bone imaging99mTc radiopharmaceuticals

The radiochemical purity of MDP and HEDP has been determined by means of gel chromatography on Sephadex and thin layer chromatography on plastic foil silica gel. The comparison of the two radiopharmaceuticals shows equal level of complex formation with^99mTc. The biodistribution demonstrated that the application of HEDP allows earlier scanning than MDP. MDP and HEDP show equal effectivity during the clinical investigations. There is no significant difference in the radiochemical purity within six hours after the reconstitution of the freeze-dried kits. HEDP kit demonstrates shorter period of accumulation and equivalent complex formation levels, so it can be used in routine nuclear medicine diagnostics together with MDP kit.     

Stability of L-[S-methyl-11C]methionine solutions

For clinical PET studies L-[S-methyl-¹¹C]methionine ([¹¹C]MET) solutions have been prepared in both high doses and specific activities (up to 48.1 GBq and 370 GBq/mmol, respectively) with high radiochemical purity (>99%). The stability of these preparations was investigated by HPLC to ensure the radiopharmaceutical efficacy during the usable shelf life. Under our routine conditions the observed radiochemical purity loss never exceeded 3.5% one hour after EOS. The decomposition rate was affected by total activity and chemical composition of the solutions.     

Optimization of fundamental parameters in routine production of 90Y-hydroxyapatite for radiosynovectomy

Hydroxyapatite was applied as a carrier adsorbing ⁹⁰Y³⁺ ions for ⁹⁰Y-HA colloid production. The radiopharmaceutical colloid was prepared by adding an acidic solution of ⁹⁰YCl₃ to HA suspension in saline solution. Effective parameters on labeling of ⁹⁰Y-HA were evaluated. Adsorption and cation-exchange properties were studied using inductively coupled plasma elemental analysis and N₂ adsorption–desorption isotherm method. Radionuclidic purity was over 99.9 %. Labeling yield and radiochemical purity were >99 %. Radiochemical purity was evaluated also in human albumin for 7 days at 37 °C. Biodistribution studies have shown complete retention of injected radioactivity at the administration site up to 72 h.     

Preparation of Iodine-131 Labeled Hippuran by Exchange Method

I^131?labeled Hippuran was prepared by isotopic exchange reaction between ortho-iodohippuric acid and I¹³¹-iodide. Special emphasis was placed on the separation of I^131?labeled Hippuran and its analysis with respect to the radiochemical purity. It was found that the prepared I¹³¹-labeled Hippuran meets the requirement as the radiopharmaceutical to be used for medical purpose.     

Fully Automated Macro- and Microfluidic Production of [68Ga]Ga-Citrate on mAIO® and iMiDEVTM Modules

⁶⁸Ga-radionuclide has gained importance due to its availability via ⁶⁸Ge/⁶⁸Ga generator or cyclotron production, therefore increasing the number of ⁶⁸Ga-based PET radiopharmaceuticals available in clinical practice. [⁶⁸Ga]Ga-citrate PET has been shown to be prominent for detection of inflammation/infection of the musculoskeletal, gastrointestinal, respiratory, and cardiovascular systems. Automation and comparison between conventional and microfluidic production of [⁶⁸Ga]Ga-citrate was performed using miniAllInOne^® (Trasis) and iMiDEV™ (PMB-Alcen) synthetic modules. Fully automated procedures were elaborated for cGMP production of tracer. In order to facilitate the tracer approval as a radiopharmaceutical for clinical use, a new method for radiochemical identity determination by HPLC analysis to complement standard TLC radiochemical purity measurement was developed. The results showed higher radiochemical yields when using MCX cartridge on the conventional module mAIO^®, while a PS-H+ cation exchanger was shown to be preferred for integration into the microfluidic cassette of iMiDEV™ module. In this study, the fully automated radiosynthesis of [⁶⁸Ga]Ga-citrate using different synthesizers demonstrated reliable and reproducible radiochemical yields. In order to demonstrate the applicability of [⁶⁸Ga]Ga-citrate, in vitro and in vivo studies were performed showing similar characteristics of the tracer obtained using macro- and microfluidic ways of production.     

Preparation of carbon-11 labelled acetate and palmitic acid for the study of myocardial metabolism by emission-computerised axial tomography

Methods have been developed for the labelling of acetate and palmitic acid with the positron-emitting radionuclide,¹¹C (T=20.4 min). Labelling was achieved via carbonation of the appropriate alkyl magnesium bromide (methyl magnesium bromide or n-pentadecyl magnesium bromide) with¹¹C-labelled carbon dioxide produced by the¹⁴N(p, α)¹¹C nuclear reaction. The radiochemical yield and speed of each method of labelling are such that a radiochemically pure product is obtained in injectable form and in activity (>10 mCi) suitable for the study of myocardial metabolism by emission-computerised axial tomography. High pressure liquid chromatography and thin layer chromatography were used to assess the radiochemical purity of each radiopharmaceutical. The specific activity of¹¹C-labelled acetate was estimated by an enzymic procedure to be greater than 0.5 Ci/μmole.     

Labeling of Sertraline with 131I and investigation of its radiopharmaceutical potential

Sertraline is an antidepressant drug. Sertraline was labeled with ¹³¹I by using iodogen method. Labeling yield was 85–90% and specific activity was approximately 64.75 GBq/mmol. The purification of radioiodinated Sertraline was performed by Sep Pak C-18 plus and the radiochemical purity was determined to be over 99%. Biodistribution studies were carried out by male Albino Wistar rats. The percentage of injected radioactivity per gram of tissue was calculated, and these data versus time curves were generated for organs and brain regions. The results showed that ¹³¹I labeled Sertraline may be a promising radiopharmaceutical for the investigation of serotonin 5-HT receptor functions of brain.     

Radiochemical quality control of99mTc-labelled radiopharmaceuticals

Two methods for the determination of radiochemical purity of preparations labeled with^99mTc are described. Paper chromatography was used for separation of reduced^99mTc and free pertechnetate from the labeled radiopharmaceutical. Whatman 3MM paper was used first with a acetone and then with 1N NaCl, as the mobile phase. Instant thin layer chromatography was performed for comparison. The electrophoretic method was also applied, using 0.05 M Na-acetate and 0.017 M NaCl. Biodistribution of^99mTc-DMSA in the organs of experimental animals was followed in order to verify chemical control methods.     

Indium-111 labeled bleomycin for targeting diagnosis and therapy of liver tumor: optimized preparation,biodistribution and SPECT imaging with xenograft models

In this work, the preparation of ¹¹¹In radiolabeled bleomycin (¹¹¹In-BLM) was optimized systematically and used for SPECT imaging of liver cancer xenograft models. ¹¹¹In-BLM with a high radiochemical yield (>?99%) could be obtained at pH 0.5–1 at a mixture ratio of 9:1 (¹¹¹In/BLM, mCi/mg). The radiochemical purity of ¹¹¹In-BLM retained?>?99% in either buffers or serum for 3 days. Biodistribution of ¹¹¹In-BLM revealed its excellent stability in vivo. The SPECT imaging studies showed ¹¹¹In-BLM has great specificity to liver tumor xenograft. All the results implied ¹¹¹In-BLM is a potential radiopharmaceutical for targeting diagnosis and therapy of liver tumor.