Technetium-99m Radiopharmaceuticals Research Articles

Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging.

Background: The accurate diagnosis of bacterial infections remains a critical challenge in clinical practice. Traditional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to distinguish bacterial infections from sterile inflammation. Nuclear medicine, such as technetium-99m (99mTc) radiopharmaceuticals, offers a promising alternative due to its ideal characteristics. Methods: This study explores the development of [2 + 1] mixed-ligand 99mTc-labeled ciprofloxacin dithiocarbamate (Cip-DTC) complexes combined with various phosphine ligands, including triphenylphosphine (PPh3), tris(4-methoxyphenyl)phosphine (TMPP), methyl(diphenyl)phosphine (MePPh2), dimethylphenylphosphine (DMPP), and 1,3,5-triaza-7-phosphaadamantane (ADAP). The characterization of 99mTc-complexes was conducted using rhenium analogs as structural models to ensure similar coordination. Results: Stability studies demonstrated the high integrity (97-98%) of the complexes under various conditions, including cysteine and histidine challenges. Lipophilicity studies indicated that complexes with higher logD7.4 values (1.6-2.7) exhibited enhanced tissue penetration and prolonged circulation. Biodistribution studies in Swiss Albino mice with induced infections and aseptic inflammation revealed distinct patterns. Specifically, the complex fac-[99mTc(CO)3(Cip-DTC)(PPh3)] (2') showed high infected/normal muscle ratios (4.62 at 120 min), while the complex fac-[99mTc(CO)3(Cip-DTC)(TMPP)] (3') demonstrated delayed but effective targeting (infected/normal muscle ratio of 3.32 at 120 min). Conclusions: These findings highlight the potential of 99mTc-labeled complexes as effective radiopharmaceuticals for the differential diagnosis of bacterial infections, advancing nuclear medicine diagnostics. Future studies will focus on optimizing molecular weight, lipophilicity, and stability to further enhance the diagnostic specificity and clinical utility of these radiopharmaceuticals.

Análise da Produção Científica em Oncológicos na Base de Dados Scopus

According to data from the United Nations, cancer is the second leading cause of death in the world. Due to its chemical properties, technetium-99m remains the most used radioisotope in the diagnosis of cancers. Thus, the present work analyzed through bibliometrics the characteristics of the world scientific production on technetium-99m, presented in articles from the Scopus database between 2001 and 2021. The search terms “(99mtc OR technetium OR technetium-99m) were used. AND (cancer OR tumor)”, with the filters “Title” and “Summary” in the search fields united by the Boolean operator “OR”. Then, the data were exported so that the construction and visualization of bibliographic networks could be carried out using the VOSviewer® program. The analysis of articles and journals showed that, in the number of publications, the United States, the Journal of Nuclear Medicine, The Netherlands Cancer Institute and the author Mishra, A.K. (India). Regarding the analyzes analyzed with VOSviewer®, the following stand out: the author Shuang Liu (co-citation of authors); and the words article and human (co-occurrence of keywords); Fan Wang (bibliographic coupling). It is hoped that this study will help stakeholders who have carried out research on technetium-99m radiopharmaceuticals to understand the scenario of scientific production.

Oldie but Goodie: Is Technetium-99m Still a Treasure Trove of Innovation for Medicine? A Patents Analysis (2000-2022).

Technetium-99m is the workhorse of diagnostic nuclear medicine. The aim of the work is to analyze the technetium-99m patents since 2000 to photograph its innovation. QUESTEL's ORBIT Intelligence system was used for the collection of technetium inventions disclosed in patents and patent applications in more than 96 countries in the period 2000-2022; 2768 patent documents were analyzed. Patent counting and analysis have shown that SPECT imaging using technetium-99m radiopharmaceuticals is still robust. The introduction of new technetium-99m radiopharmaceuticals into clinical routine goes beyond successful trials. In eastern economies, such as China and other emerging markets, patent applications are on the rise, while those in developed western countries are stagnating, with some exceptions for the United States. But despite the difficulties, academic and industrial research on these tracers remains essential for the development of nuclear medicine.

Fabrication of epoxy-resin-based bismuth-oxide powder radioactive container for Technetium-99m and Iodine-131 radiopharmaceuticals

Lead shielding materials are standard for radiation protection to limit exposure for patients and health care workers. However, lead is both heavy and highly toxic. The benefits of non-lead products are becoming and interesting because they offer the benefits of being cheaper, lighter and non-toxicity. This study has explored the radiation shielding efficacy of bismuth oxide (Bi2O3) loaded into the epoxy-resin for a Technetium-99m (99mTc) and Iodine-131 (131I) radiopharmaceutical container. Gamma ray attenuation parameters of the samples were investigated and compared with original lead shielding. The results showed that linear attenuation coefficient and percentage attenuation are increased with increasing filler loading. In contrast, the half-value layer values were decreased when more Bi2O3 was added. The 50 wt% Bi2O3 provided the best gamma ray attenuation efficacy with attenuations of 99.99% and 99.87% at gamma ray energy 140 and 364 keV, respectively. In comparison to lead, the 50 wt% Bi2O3 presented a slightly different attenuation of about 1.64%, while the heaviness was halved. Therefore, we hypothesize that Bi2O3 loaded into the epoxy-resin has gamma ray shielding potential for containing 99mTc and 131I radiopharmaceuticals while both reducing cost and weight.

Technetium-99m Radiopharmaceuticals for Ideal Myocardial Perfusion Imaging: Lost and Found Opportunities.

The favorable nuclear properties in combination with the rich coordination chemistry make technetium-99m the radioisotope of choice for the development of myocardial perfusion tracers. In the early 1980s, [99mTc]Tc-Sestamibi, [99mTc]Tc-Tetrofosmin, and [99mTc]Tc-Teboroxime were approved as commercial radiopharmaceuticals for myocardial perfusion imaging in nuclear cardiology. Despite its peculiar properties, the clinical use of [99mTc]Tc-Teboroxime was quickly abandoned due to its rapid myocardial washout. Despite their widespread clinical applications, both [99mTc]Tc-Sestamibi and [99mTc]Tc-Tetrofosmin do not meet the requirements of an ideal perfusion imaging agent due to their relatively low first-pass extraction fraction and high liver absorption. An ideal radiotracer for myocardial perfusion imaging should have a high myocardial uptake; a high and stable target-to-background ratio with low uptake in the lungs, liver, stomach during the image acquisition period; a high first-pass myocardial extraction fraction and very rapid blood clearance; and a linear relationship between radiotracer myocardial uptake and coronary blood flow. Although it is difficult to reconcile all these properties in a single tracer, scientific research in the field has always channeled its efforts in the development of molecules that are able to meet the characteristics of ideality as much as possible. This short review summarizes the developments in 99mTc myocardial perfusion tracers, which are able to fulfill hitherto unmet medical needs and serve a large population of patients with heart disease, and underlines their strengths and weaknesses, the lost and found opportunities thanks to the developments of the new ultrafast SPECT technologies.

Assessment of residual activities of Technetium-99m radiopharmaceuticals to plastic syringes in nuclear medicine scans: 1-year experience at NORIN Nawabshah, Pakistan

Background: Technetium-99m radioisotope is the backbone of any nuclear medicine institute. It is well known that various 99mTclabeled radiopharmaceuticals may get absorbed into the plastic syringes. The consequences of this adsorption are inadequate or inconsistent absorbed dose which produces the inappropriate diagnostic response in patients. The aim of our study was to investigate the true activity administrated to patients and also compare the results of residual activities of the same dose by using different volumes of syringes. Methods: A total 946 measurements were analyzed in which patients were injected with either 3 or 5 ml syringes and 99mTc was labeled with different pharmaceuticals, i.e., mercaptoacetyltriglycine-3, methoxy-iso-butyl isonitrile, methylenediphosphonic acid (MDP), and technetium pertechnitate. Residual activity was measured for every patient. Results: The 3 ml syringes have less average retention rate for any radiopharmaceutical as compared to 5 ml syringes. Residual activity for MDP is lower when compared to other radiopharmaceutical for both volumes of syringes. Maximum residual activity for 5 ml syringes happens to be 3.42% of dispensed activity, while for 3 ml syringes it is 2.74% of dispensed activity. The mean effective activities were within the recommended range of EANM and PNRA guidelines. Conclusion: For all radiopharmaceuticals and both syringes, average residual activity remained well under 1.5% of the activity drawn into syringes, which is insignificant when compared to previous reported results and may not alter the resultant image quality to a larger extent. In hospital, practices should be encouraged to reduce the residual activity as low as possible.

Effect of Ursodeoxycholic Acid on the Biodistribution and Excretion of Technetium-99m Radiopharmaceuticals in Rat: A Potential Image Quality Enhancer.

PurposeThis study aimed to investigate the effect of ursodeoxycholic acid (UDCA) on the biodistribution and excretion of technetium-99m (Tc-99m)-labeled radiopharmaceuticals.Materials and MethodsTc-99m hydroxy-methylene-diphosphonate (HDP), Tc-99m pertechnetate, and Tc-99m dimercaptosuccinic acid (DMSA) were injected via the tail vein of rats. After 30 min, the control group was administered saline, and the UDCA group was given UDCA orally. Scintigraphy images were acquired after 30 min and 1, 2, 3, and 4 h. Radioactivity and rate of change were compared. Tc-99m mercaptoacetyltriglycine (MAG3) imaging was also performed.ResultsIn image analysis of Tc-99m HDP, radioactivity of the buttock was lower in the UDCA group at 4 h. Rates of change in the buttock were significantly different at 3 h–30 min and 4 h–30 min, and buttock radioactivity in the UDCA group had decreased more. In analysis of Tc-99m pertechnetate, radioactivity of the buttock was higher in the control group. Rates of change in the thyroid gland and buttock were different at 1 h–30 min, 3 h–30 min, and 4 h–30 min, with radioactivity in the UDCA group decreasing more. In the analysis of Tc-99m DMSA, while the radioactivity of the kidneys in the control group showed little decrease at 1 h–30 min, that in the UDCA group increased. In the analysis of Tc-99m MAG3 images, radioactivity and radioactivity/total body radioactivity (TBA) values for the kidneys were higher in the UDCA group at 2 min. At 5 and 10 min, radioactivity/TBA values for soft tissue in the UDCA group were lower than those in the control group.ConclusionThis study demonstrated that administration of UDCA increases renal excretion and soft tissue clearance of radiopharmaceuticals. This investigation could contribute to the broadening of applications of UDCA.

Validation of a cost-effective alternative for a radiochromatography method to be used in a developing country

IntroductionThe radiochemical purity (RCP) of technetium-99m labelled radiopharmaceuticals (RP) is important to ensure optimal scintigraphic image quality. In low-income settings, it may not be possible to use compendial analytical methods or expensive equipment for radiochemical purity analysis. All radiochemical analysis methods should however be validated against compendial or otherwise proven methods. To ensure the efficacy of RP prepared at Yaoundé General Hospital (YGH) Cameroon, this study cross-validated a cost-effective routine chromatographic method using a simple survey meter technique. A GMP-compliant method used at the University Medical Center Groningen (UMCG), the Netherlands was used as the comparator.MethodsSestamibi, HMDP and DMSA kits currently used at YGH were reconstituted at UMCG with about 2000 MBq of freshly eluted sodium pertechnetate as described by the manufacturer, and spiked with eluate of the same generator to obtain a range of impurity concentrations. Samples of technetium-99m RP were spotted on 1 × 10 cm iTLC-SG strips and developed in appropriate mobile phases. Each strip was first scanned on the chromatogram-scanner used at the UMCG (standard method), and immediately thereafter the strip was cut in two pieces and radioactivity from each portion was counted with a small survey meter from YGH. The percentage RCP for each TLC strip was calculated using both counting methods. Internationally recommended validation parameters and acceptance criteria were used. Student’s paired t-test or ANOVA were used with ‘no significant difference’ designated at a 95% confidence-interval (P ≥ 0.05). Linearity of the survey meter was determined for Tc-99m. Readings obtained with the survey meter were also plotted against the scanner results.Results and discussionThe proposed method proved to be accurate (CV of mean RCP < 2), precise (RSD < 2%), linear (slope close to 1, r2 ≥ 0.99) within the RCP range of approximately 80% to 100%, and robust (P > 0.05). LOD and LOQ were determined for the survey meter. Specificity depends on chemical separation. As we were validating the suitability of a method to quantify radioactivity, specificity was not included in the validation parameters.ConclusionThe proposed method compared well with the standard method and is suitable as a reliable low cost method for limited resource settings.

Nitrido Technetium-99 m Core in Radiopharmaceutical Applications: Four Decades of Research

The knowledge on element 43 (Tc) of the periodic table, built over the years through the contributions given by the close relationship between chemistry and nuclear medicine, allowed the development of new and increasingly effective radiopharmaceuticals useful both as perfusion and target specific imaging agents for SPECT (single photon emission tomography). Among the manifold Tc-compounds, Tc(V) nitrido complexes played a relevant role in the search for new technetium-99m radiopharmaceuticals, providing efficient labeling procedures that can be conveniently exploited for the design and synthesis of agents, also incorporating small organic molecules or peptides having defined structural features. With this work, we present an overview of four decades of research on the chemistry and on the nuclear medicine applications of Tc(V) nitrido complexes.

Sterility assurance of technetium-99m radiopharmaceuticals: no specific air conditions are required for their preparation, storage and dispensation.

The aim of this study was to ascertain whether the extemporaneous technetium-99m radiopharmaceuticals - prepared by closed procedures - maintain or not sterility throughout their lifespan regardless the quality of the environmental air where they are prepared, stored and dispensed, provided that the basic aseptic rules for closed procedures are followed. Three different types of assays were performed in this study: 1) sterility tests of each and every one of the vials with the remains of technetium-99m radiopharmaceuticals, which have been prepared in our hospital radiopharmacy during three years without any special environmental air conditions; 2) integrity tests of punctured rubber plug closures using both microbial challenge testing and dye ingress testing; and 3) simulation of the dispensing process using a liquid growth medium. Sterility tests of more than 6,000 vials with the remains of technetium-99m radiopharmaceuticals - prepared without any special ambient air conditions - were performed, all of them with a negative result (no growth of microorganisms occurs). The integrity of punctured rubber plugs closure was sufficiently proven under extreme conditions by two different methods. The maintenance of sterility during the dispensing process of technetium-99m radiopharmaceuticals was also proven by simulation of the dispensing process using a liquid growth medium. This study strongly supports that it is not necessary any special ambient air conditions to prepare, store and dispense extemporaneous technetium-99m radiopharmaceuticals in order to preserve their sterility when the basic aseptic rules for closed procedures are followed.

A Picture of Modern Tc-99m Radiopharmaceuticals: Production, Chemistry, and Applications in Molecular Imaging

Even today, techentium-99m represents the radionuclide of choice for diagnostic radio-imaging applications. Its peculiar physical and chemical properties make it particularly suitable for medical imaging. By the use of molecular probes and perfusion radiotracers, it provides rapid and non-invasive evaluation of the function, physiology, and/or pathology of organs. The versatile chemistry of technetium-99m, due to its multi-oxidation states, and, consequently, the ability to produce a variety of complexes with particular desired characteristics, are the major advantages of this medical radionuclide. The advances in technetium coordination chemistry over the last 20 years, in combination with recent advances in detector technologies and reconstruction algorithms, make SPECT’s spatial resolution comparable to that of PET, allowing 99mTc radiopharmaceuticals to have an important role in nuclear medicine and to be particularly suitable for molecular imaging. In this review the most efficient chemical methods, based on the modern concept of the 99mTc-metal fragment approach, applied to the development of technetium-99m radiopharmaceuticals for molecular imaging, are described. A specific paragraph is dedicated to the development of new 99mTc-based radiopharmaceuticals for prostate cancer.

Technetium Complexes and Radiopharmaceuticals with Scorpionate Ligands

Scorpionate ligands have played a crucial role in the development of technetium chemistry and, recently, they have also fueled important advancements in the discovery of novel diagnostic imaging agents based on the γ-emitting radionuclide technetium-99m. The purpose of this short review is to provide an illustration of the most general and relevant results in this field, however without being concerned with the details of the analytical features of the various compounds. Thus, emphasis will be given to the description of the general features of technetium complexes with scorpionate ligands including coordination modes, structural properties and an elementary bonding description. Similarly, the most relevant examples of technetium-99m radiopharmaceuticals derived from scorpionate ligands and their potential interest for nuclear imaging will be summarized.

188Re(V) Nitrido Radiopharmaceuticals for Radionuclide Therapy.

The favorable nuclear properties of rhenium-188 for therapeutic application are described, together with new methods for the preparation of high yield and stable 188Re radiopharmaceuticals characterized by the presence of the nitride rhenium core in their final chemical structure. 188Re is readily available from an 188W/188Re generator system and a parallelism between the general synthetic procedures applied for the preparation of nitride technetium-99m and rhenium-188 theranostics radiopharmaceuticals is reported. Although some differences between the chemical characteristics of the two metallic nitrido fragments are highlighted, it is apparent that the same general procedures developed for the labelling of biologically active molecules with technetium-99m can be applied to rhenium-188 with minor modification. The availability of these chemical strategies, that allow the obtainment, in very high yield and in physiological condition, of 188Re radiopharmaceuticals, gives a new attractive prospective to employ this radionuclide for therapeutic applications.

Quality control on radiochemical purity in Technetium-99m radiopharmaceuticals labelling: three years of experience on 2280 procedures.

Objective: the purpose of this study was to offer an example of evaluations of the ISO9001 certified internal quality assurance (QA) system of 99mTc-radiopharmaceutical preparations and quality control in vivo use, using industrial kits and generators in order to identify possible sources of errors in the procedures labeling and quality control procedures. Methods: The study was performed at a single institution over a period of three years (July 1st, 2011 - July 1st, 2014), and included a total of 2280 radiopharmaceutical preparations prepared by four different technologists. All the radiopharmaceutical preparations and quality controls were performed according to each SPC provided by the manufacturer. The radiopharmaceutical preparations were the following (trade names are reported in brackets): 99mTc-albumin colloid [Nanocoll] (n=349), 99mTc-oxidronate [Technescan®hdp] (n=701), 99mTc-exametazime [Ceretec] (n=169), 99mTc-sestamibi [Cardiolite] (n=92), 99mTc-albumin aggregated [Technescan®lyomaa] (n=140), 99mTc-tetrofosmin [Myoview]) (n=567), 99mTc-diethylene triamine pentacetic acid [Technescan®dtpa] (n=254), and 99mTc-dimercapto succinic acid [Renocis®] (n=8). Data were analyzed to determine the number and type of radiopharmaceutical labelling failure and to derive the sources of these failures to define corrective actions and optimize the quality assurance program. Results: A total of 2280 procedures were performed and recorded. Following the quality control procedure six out of the 2280 preparations (0.26%) were non-conforming for clinical use with the RCP limits indicated in the SPC. Five of these were due to gross technical errors in measurements and manual procedures and were immediately repeated, returning within the limits of acceptability. The sixth failure was due to short incubation time, though compliant with the manufacturer’s instructions. Conclusions: We concluded that the quality of the final product depends on a controlled production system based on the implementation of specific standard operating procedures (ISO9001, SOP) for each radiopharmaceutical production, according to strict adherence to the SPC of each radiopharmaceutical. Based on these conclusions, in our opinion every quality control suggesting a possible error in the synthesis procedure recommended in the SPC should be immediately reported to the manufacturer, for a revision of the SPC, as well as to the regulatory agencies for an alert. This strategy may in fact allow the continuous improvement of the labelling procedures and therefore the optimization of the quality control procedures frequency to ensure both patients safety and a more rational management of resources for economic sustainability. (www.actabiomedica.it)

Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [(99m)Tc(MIBI)₆

Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI)6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI)6]+ since impurities such as99mTc-reduced-hydrolyzed (RH),99mTcO4 - and [99mTc(cysteine)2]-complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

Preparation and labeling of technitium-99m kit In pharmaceutical grade clean room

Technetium-99m radiopharmaceuticals are in widespread use owing to the availability and affordability of 99Mo/99m-Tc generators and the variety of kits for formulating the desired products. Together, they provide an array of specific tools for diagnosing a large number of diseases affecting the bones and major organs of the body such as the heart, brain, liver, kidney and thyroid. Nuclear medicine requires high quality radiopharmaceuticals and kits that are safe for administration and efficacious for a given application. In Bangladesh, no commercial production was done before this. This paper presents the theoretical basis of and describes the procedures for preparing three selected kits. Details of the ingredients are also included. The procedures described here can be used to develop manuals and standard operating procedures in Bangladesh. This report is expected to serve as a guide to radiopharmaceutical manufacturing centers and centralized pharmacies involved in the production of such kits in the current environment of Bangladesh. It will be a useful resource for many hospital radio pharmacy departments that routinely use the kits to compound 99m-Tc radiopharmaceuticals. Three kits namely: MDP, DMSA and DTPA were prepared. Paper Chromatography was involved to disparate the polar and non-polar part of the kit-solution and finally gamma spectrometry (HPGe) to deduce the Radiochemical Purity (RCP). By reviewing purity values, it was found that only DMSA has passed the 95% barrier which is the required percentage for safe application. This paper suggests that the findings require more practice and involve such exquisite points, which will contribute in the production of Tc-99m vivo-kits at Radioisotope Production Division (RIPD), AERE, INST and in their projected future mass production successfully. DOI: http://dx.doi.org/10.3329/jce.v27i2.17798 Journal of Chemical Engineering, IEB Vol. ChE. 27, No. 2, December 2012: 31-35

Evaluation of alternative rapid thin layer chromatography systems for quality control of technetium-99m radiopharmaceuticals

Whatman 3MM™ and Tec-Control™ systems were evaluated as ITLC-SG alternatives for 99mTc-radiopharmaceuticals. They compare well in accuracy and reproducibility, and are faster and more convenient than ITLC-SG. Tec-Control™ radiochemical purity values for 99mTc-sestamibi were more conservative than ITLC-SG. Full solvent migration was not reproduced for 99mTc-tetrofosmin in Tec-Control™, and for this Whatman 3MM™ is preferred. Developing times were 10–15min, 7–9min and ~1min for ITLC-SG, Whatman 3MM™ and Tec-Control™, respectively. Overall, Tec-Control™ strips are preferred due to speed and ease of use.

Airway Deposition of Nebulized Gene Delivery Nanocomplexes Monitored by Radioimaging Agents

Receptor-targeted nanocomplexes are nonviral vectors developed for gene delivery to the airway epithelium for the treatment of pulmonary disease associated with cystic fibrosis. The present study aimed to optimize the delivery of the nanocomplex by nebulization, and to monitor the in vivo deposition of radiolabeled vector in the airways of a large animal model by γ-camera scintigraphy. Large White weaner pigs were nebulized with nanocomplexes mixed with technetium-99m radiopharmaceuticals. The aerosol deposition scans suggested that the nebulized radiovectors were deposited mainly in the trachea-main bronchi and in the midregion of the lungs. The plasmid biodistribution, assessed by real-time PCR, correlated with the scintigraphy images. The highest plasmid copy numbers were found in the bronchial areas and in the tissues proximal to the main bronchi bifurcation. Immunohistochemistry detected transgene expression in the tracheal and bronchial ciliated epithelium. Histological analysis of lung tissue showed no evidence of inflammation, and no increase in inflammatory cytokines or inflammatory cells was detected in the bronchoalveolar lavage. The deposition of nebulized nanocomplexes coassociated with technetium-99m can be monitored by nuclear medicine techniques. The use of a noninvasive strategy to follow the delivery of the vector could improve the clinical management of patients undergoing cystic fibrosis gene therapy.

Radio-UHPLC: A tool for rapidly determining the radiochemical purity of technetium-99m radiopharmaceuticals?

Determining the radiochemical purity (RCP) of technetium-99m (99mTc) radiopharmaceuticals using the method described in the package insert is a time-consuming process, requiring particular attention in order to achieve accurate RCP results. The purpose of this study was to evaluate whether radio-ultra high performance liquid chromatography (radio-UHPLC) may be an alternative method for RCP testing of 99mTc-tetrofosmin, 99mTc-MAG3 and 99mTc-sestamibi. Results obtained using radio-UHPLC were in excellent agreement with the standard method, with total analysis time being reduced to less than 3min.

Investigation of isomer formation upon coordination of bifunctional histidine analogues with 99mTc/Re(CO)3

Histidine is a convenient tridentate chelator used in the synthesis of technetium-99m radiopharmaceuticals, as it can be pendantly attached to a biomolecule for molecular imaging applications. Once coordinated, it forms a neutral complex that is capable of forming diastereomers at the alpha amine of the histidine. This is demonstrated through the synthesis and characterization of four different histidine chelators; three small molecule chelators, which consist of a benzylated histidine at the alpha amine, and one modified dipeptide, containing a phenylalanine derivative at the C-terminus and a histidine at the N-terminus. Upon rhenium coordination, two products are observed, each having the desired exact mass of the metal-containing species. The two products have been characterized through LC-MS, (1)H, gCOSY, NOESY and ROESY NMR experiments, and the relative stereochemistry determined. The implications of diastereomer formation when using this chelation system for creating molecular imaging agents is also discussed.