Technetium-99m radiolabeling of graphene quantum dots (GQDs) as a new probe for glioblastoma tumor imaging.

PURPOSE: Cancer diagnosis involves a multi-step process. Accurate identification of the tumor, staging and development of cancer cells is crucial for selecting optimal treatments to minimize disease recurrence. Quantum dots (QDs) represent an exciting class of fluorescent nanoprobes in molecular detection and targeted tumor imaging. MATERIALS AND METHODS: In this study, graphene quantum dots (GQDs) were synthesized by pyrolysis of citric acid (CA) as a carbon precursor under high temperatures. The morphology of the obtained GQDs was first characterized using physical (TEM and DLS) and spectroscopic (fluorescence, FTIR and UV-Vis) methods. In the following,99mTc-labeled GQDs were prepared in the presence of SnCl2.2H2O as a reducing agent between 95 and 100 °C. The biodistribution and tumor targeting efficiency of radiolabeled GQDs as a novel agent for C6 glioma tumor scintigraphy in an animal model were evaluated. Furthermore, organ uptake, human serum albumin binding and tumor accumulation were measured. RESULTS: The TEM image of the prepared GQDs showed a relatively uniform size distribution in the range of diameter 6-9 nm and spherical shape. Radiolabeled GQDs showed a radiochemical yield of >97% (n = 3). Through incubation in human serum, almost 15% of 99mTc-labeled GQDs degraded after 6 h. The amount of uptake in xenograft models of glioma C6 rats was 1.10 ± 0.36% of injection dose per gram after 1 h. The kidneys, intestinal and glioma tumor sites were observed via scintigraphy imaging. CONCLUSION: Our data suggest that 99mTc-labeled GQDs, as a new radiotracer, efficiently accumulate in the tumor site and could be included as a radiotracer for detecting glioma tumors.

Transplanted Murine Tumours SPECT Imaging with 99mTc Delivered with an Artificial Recombinant Protein.

99mTc is a well-known radionuclide that is widely used and readily available for SPECT/CT (Single-Photon Emission Computed Tomography) diagnosis. However, commercial isotope carriers are not specific enough to tumours, rapidly clear from the bloodstream, and are not safe. To overcome these limitations, we suggest immunologically compatible recombinant proteins containing a combination of metal binding sites as 99mTc chelators and several different tumour-specific ligands for early detection of tumours. E1b protein containing metal-binding centres and tumour-specific ligands targeting integrin αvß3 and nucleolin, as well as a short Cys-rich sequence, was artificially constructed. It was produced in E. coli, purified by metal-chelate chromatography, and used to obtain a complex with 99mTc. This was administered intravenously to healthy Balb/C mice at an activity dose of about 80 MBq per mouse, and the biodistribution was studied by SPECT/CT for 24 h. Free sodium 99mTc-pertechnetate at the same dose was used as a reference. The selectivity of 99mTc-E1b and the kinetics of isotope retention in tumours were then investigated in experiments in C57Bl/6 and Balb/C mice with subcutaneously transplanted lung carcinoma (LLC) or mammary adenocarcinoma (Ca755, EMT6, or 4T1). The radionuclide distribution ratio in tumour and adjacent normal tissue (T/N) steadily increased over 24 h, reaching 15.7 ± 4.2 for EMT6, 16.5 ± 3.8 for Ca755, 6.7 ± 4.2 for LLC, and 7.5 ± 3.1 for 4T1.

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.

Synthesis and Biological Evaluation of Novel Cationic Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivative for Epidermal Growth Factor Receptor Targeting.

Background/Objectives: Epidermal growth factor receptor (EGFR) plays a vital role in cell proliferation and survival, with its overexpression linked to various malignancies, including non-small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (TKIs) are a key therapeutic strategy, acquired resistance and relapse remain challenges. This study aimed to synthesize and evaluate novel rhenium-based complexes incorporating EGFR TKIs to enhance anticancer efficacy, particularly in radiosensitization. Methods: We synthesized a rhenium tricarbonyl complex (Complex 2) and its 99mTc analog (Complex 2') by incorporating triphenylphosphine instead of bromine as the monodentate ligand and PF6- as the counter-ion, resulting in a positively charged compound that forms cationic structures. Cytotoxicity and EGFR inhibition were evaluated in A431 cells overexpressing EGFR using MTT assays, Western blotting, and flow cytometry. Radiosensitization was tested through MTT and clonogenic assays. The 99mTc complex's radiochemical yield, stability, and lipophilicity were also assessed. Results: Complex 2 exhibited significant cytotoxicity with an IC50 of 2.6 µM and EGFR phosphorylation inhibition with an IC50 of 130.6 nM. Both complex 1 and 2 induced G0/G1 cell cycle arrest, with Complex 2 causing apoptosis. Radiosensitization was observed at doses above 2 Gy. Complex 2' demonstrated high stability and favorable lipophilicity (LogD7.4 3.2), showing 12% cellular uptake after 30 min. Conclusions: Complexes 2 and 2' show promise as dual-function anticancer agents, offering EGFR inhibition, apoptosis induction, and radiosensitization. Their potential as radiopharmaceuticals warrants further in-depth investigation in preclinical models.

Unexpected Extrarenal Accumulation of Tc-99m Ethylene Dicysteine in a Case of Liposarcoma.

The technetium-99m ethylene dicysteine (Tc-99m EC) is a radiopharmaceutical used for renal scintigraphy, a noninvasive imaging technique that assesses kidney function as well as urinary tract obstruction. We describe the extrarenal Tc-99m EC uptake in a 70-year-old man with recurrent well-differentiated abdominal liposarcoma. In the present case, both liposarcoma lesions which were diagnosed by abdominal CT scan showed heterogeneous accumulation of the Tc-99m EC.

Radiolabeling and preclinical evaluation of technetium-99m labeled colistin.

INTRODUCTION: Antibiotic resistance is a burden on the healthcare system. In present study, we have labeled an antibiotic named Colistimethate sodium (CMS) with technetium-99m (99mTc) to develop a SPECT based imaging tracer. METHODS: We standardised the labeling using 0.5-2 mg of CMS (in water) using stannous chloride dihydrate as a reducing agent followed by addition of 370 ± 74 MBq of 99mTc. A group of mice were injected intravenously (in tail vein) with 4-6 MBq of [99mTc]Tc-CMS diluted with saline and euthanized at various time intervals. microSPECT Imaging (ϒ-eye) was acquired to study the biodistribution in the healthy mice. RESULTS: We standardised the labeling using 0.5 mg of colistin in 0.5 ml of saline with addition of 30 µg stannous chloride dihydrate. The retention factor value was 0.1-0.3 as compared to 0.9-1.0 for free 99mTc by TLC and retention time was found to be 14.2 ± 1.3 min as evaluated by HPLC. The biodistribution data showed uptake in lungs, spleen, and liver at 30 min but the uptake decreased in lung at 60 min. The imaging data corroborated with the biodistribution data. CONCLUSIONS: We could successfully label [99mTc]Tc-CMS 99mTc and we could study its biodistribution in healthy mice.

Equine Nuclear Medicine in 2024: Use and Value of Scintigraphy and PET in Equine Lameness Diagnosis.

Scintigraphy and Positron Emission Tomography (PET) are both nuclear medicine imaging techniques, providing functional information of the imaged areas. Scintigraphy is a two-dimensional projected imaging technique that was introduced in equine imaging in the late 1970s. Scintigraphy allows imaging of large body parts and can cover multiple areas, remaining the only technique commonly used in horses for whole body imaging. PET is a cross-sectional imaging technique, first used in horses in 2015, allowing higher resolution three-dimensional functional imaging of the equine distal limb. This manuscript will cover current use and values of these two modalities in equine lameness diagnosis.

A thiourea-bridged 99mTc(CO)3-dipicolylamine-2-nitroimidazole complex for targeting tumor hypoxia: Utilizing metabolizable thiourea-bridge to improve pharmacokinetics.

The 2-nitroimidazole based 99mTc-radiopharmaceuticals are widely explored for imaging tumor hypoxia. Radiopharmaceuticals for targeting hypoxia are often lipophilic and therefore, show significant uptake in liver and other vital organs. In this context, lipophilic radiopharmaceuticals with design features enabling faster clearance from liver may be more desirable. A dipicolylamine-NCS bifunctional chelator that could generate a thiourea-bridge up on conjugation to primary amine bearing molecule was used to synthesize a 2-nitroimidazole-dipicolyl amine ligand for radiolabeling with 99mTc(CO)3 core. Corresponding Re(CO)3-analogue was prepared to establish the structure of 2-nitroimidazole-99mTc(CO)3 complex prepared in trace level. The 2-nitroimidazole-99mTc(CO)3 complex showed a hypoxic to normoxic ratio of ~2.5 in CHO cells at 3 h. In vivo, the complex showed accumulation and retention in tumor with high tumor to blood and tumor to muscle ratio. The study demonstrated the utility of metabolizable thiourea-bridge in 2-nitroimidazole-99mTc(CO)3 complex in inducing faster clearance of the radiotracer from liver. The dipicolylamine-NCS bifunctional chelator reported herein can also be used for radiolabeling other class of target specific molecules with 99mTc(CO)3 core.

Prospective study of dual-phase 99mTc-MIBI SPECT/CT nomogram for differentiating non-small cell lung cancer from benign pulmonary lesions.

OBJECTIVES: To establish and validate a technetium 99m sestamibi (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) nomogram for predicting non-small cell lung cancer (NSCLC). Comparing the diagnostic performance of early and delayed SPECT/CT nomogram, and compare the diagnostic performance of SPECT/CT radiomics models with single SPECT and CT radiomics models. METHODS: This prospective study included 119 lesions (NSCLC: n = 92, benign pulmonary lesions: n = 27) from 103 patients (mean age: 59.68 ± 8.94 years). Patients underwent dual-phase 99mTc-MIBI SPECT/CT imaging. They were divided into the training (n = 83) and validation (n = 36) cohorts. Logistic regression, support vector machine, random forest, and light-gradient boosting machine were applied to train and determine the optimal machine learning model. Then, combining radiomics score and clinical factors, establish nomograms for diagnosing NSCLC. RESULT: CYFRA21-1 was selected for constructing the clinical model. In early imaging, the areas under the curve (AUCs) of the clinical model, radiomics model, and nomogram were 0.571, 0.830, and 0.875, respectively. The nomogram performed better than the clinical model and similarly to the radiomics model (P=0.020, P=0.216), and there are no statistically significant differences in the predictive performance between the radiomics model and the clinical model (P=0.103). In delayed imaging, the AUC was 0.643, 0.888, and 0.893, respectively. The predictive performance of the nomogram was superior compared to the clinical model and comparable to the radiomics model (P=0.042, P=0.480), and the radiomics model also demonstrated superior diagnostic performance compared to the clinical model (P=0.049). Compared to early SPECT/CT results, the AUC values of the nomogram and radiomics models in the delayed phase were higher, although no statistical differences were found (P=0.831, P=0.568). In delayed imaging, the AUC of the radiomics models for CT and SPECT was 0.696 and 0.768, respectively, SPECT/CT radiomics exhibited significant differences compared with CT and SPECT alone (P=0.042, P=0.038). CONCLUSION: Dual-phase 99mTc-MIBI SPECT/CT nomograms and radiomics models can effectively predict NSCLC, providing an economically and non-invasive imaging method for diagnosing NSCLC, moreover, these findings provide a basis for early diagnosis and treatment strategies in NSCLC patients. Delayed-phase SPECT/CT imaging may offer greater practical value than early-phase imaging for diagnosing NSCLC. However, this novel approach necessitates further validation in larger, multi-center cohorts. CLINICAL RELEVANCE: Radiomics nomogram based on SPECT/CT for discriminating NSCLC from benign lung lesions helps to aid early diagnosis and guide treatment. KEY POINTS: Nomograms, based on dual-phase SPECT/CT, was constructed to discriminate between non-small cell lung cancer and benign lesions. SPECT/CT radiomics model has better predictive performance than SPECT and CT radiomics model.

Radionuclide Solid:liquid partitioning in an aged, reducing-grout wasteform recovered from a disposal facility.

The Saltstone Disposal Facility on the Savannah River Site in South Carolina disposes of Low-Level Waste in a reducing-grout waste form. Reducing grout is presently being evaluated as a subsurface disposal waste form at several other locations in the United States, as well as in Europe and Asia. The objective of this study was to collect core samples directly from the Saltstone Disposal Facility and measure desorption distribution coefficients (Kd; radionuclide concentration ratio of saltstone:liquid; (Bq/kg)/Bq/L)) and desorption apparent solubility values (ksp; radionuclide aqueous concentration (moles/L)). An important attribute of this study was that these tests were conducted with actual aged, grout waste form materials, not small-volume simulants prepared in a laboratory. The reducing grout is comprised of blast furnace slag, Class F fly ash, ordinary portland cement, and a radioactive salt waste solution generated during nuclear processing. The grout sample used in this study underwent hydrolyzation in the disposal facility for 30 months prior to measuring radionuclide leaching. Leaching experiments were conducted either in an inert (no oxygen) atmosphere to simulate conditions within the saltstone monolith prior to aging (becoming oxidized) or they were exposed to atmosphere conditions to simulate conditions of an aged saltstone. Importantly, these experiments were designed not to be diffusion limited, that is, the saltstone was ground finely and the suspensions were under constant agitation during the equilibration period. Under oxidized conditions, measured Tc Kd values were 10 mL/g, which was appreciably greater than the historical best-estimate value of 0.8 mL/g. This difference is likely the result of a fraction of the Tc remaining in the less soluble Tc(IV) form, even after extensive oxidation during the experiment. Under oxidized and reducing conditions, the measured Ba and Sr (both divalent alkaline earth metals) Kd value were more than an order of magnitude greater than historical best-estimate values of 100 mL/g. The unexpectedly high Ba and Sr Kd values were attributed to these radionuclides having sufficient time to age (form strong bonds) in the sulfur-rich saltstone sample. Apparent ksp values under reducing conditions were 10-9 mol/L Tc and 10-13 mol/L Pu, consistent with values measured with surrogate materials. Measured apparent Ba, Sr, and Th ksp values were significantly greater than historical best-estimates. The implications of the generally greater Kd values and lower ksp values in these measurements is that these cementitious waste forms have greater radionuclide retention than was previously estimated based on laboratory studies using surrogate materials. This work represents the first leaching study performed with an actual aged, reducing-grout sample and as such provides an important comparison to studies conducted with surrogate materials, and provides high pedigree data for other programs around the world evaluating reducing grouts as a wasteform for subsurface nuclear waste disposal.

Comparison of intraoperative imaging with a portable gamma camera with extemporaneous histology in minimally invasive surgery for primary hyperparathyroidism.

INTRODUCTION: The curative treatment of primary hyperparathyroidism (PPH) is surgical and today it can be performed by minimally invasive surgery (MIS) and also be radioguided (RG) if a radiopharmaceutical with affinity for the parathyroid tissue that can be detected with gamma-detector probes or with a portable gamma camera (PGC) is injected. AIM: The objective is to assess whether intraoperative scintigraphy (GGio) with PGC can replace intraoperative pathological anatomy (APio) to determine if the removed specimen is an abnormal parathyroid. MATERIAL AND METHOD: 92 patients underwent CMI RG--HPP with PGC after the administration of a dose of 99 mTc-MIBI. The information provided by the PGC in the analysis of the excised specimens is qualitatively compared (capture yes/no) with the result of the intraoperative pathological anatomy (APio). The Gold standard is the definitive histology. RESULTS: 120 excised pieces are evaluated with GGio and APio. There were 110 agreements (95TP and 15TN) and 10 disagreements (3FP and 7FN). Of the 120 lesions, 102 were parathyroid and 18 were non-parathyroid. There was good agreement between intraoperative scintigraphy imaging (GGio) and PA, 70.1% according to Cohen's Kappa index. The GGio presented the following values ​​of Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, Positive Likelihood Ratio, Negative Likelihood Ratio and Overall Value of the Test (93.1%, 83.3%, 96.9%, 68.2%, 5.59, 0.08 and 0.92 respectively). CONCLUSION: GGio is a rapid and effective surgical aid technique to confirm/rule out the possible parathyroid nature of the lesions removed in PPH surgery, but it cannot replace histological study.

Nitrosyl and Thionitrosyl Complexes of Technetium and Rhenium and Their Reactions with Hydrotris(pyrazolyl)borates.

The very limited number of structurally known thionitrosyl complexes of technetium was increased by the synthesis of [TcII(NS)Cl3(PPh3)2] (3) and [TcII(NS)Cl3(PPh3)(OPPh3)] (4) and their reaction products with hydrotris(pyrazolyl)borates, {HB(pzR)3}-. Similar reactions were conducted with [TcI(NO)Cl2(PPh3)2(CH3CN)] and related rhenium thionitrosyls. Remarkably, most such reactions result in a rapid cleavage of the boron-nitrogen bonds of the ligands and the formation of pyrazole complexes of the two group 7 metals. Only one compound with an intact {HB(pzR)3}- ligand could be isolated: the technetium(I) complex [TcI(NO)Cl(PPh3){HB(pz)3}] (2). Other products show the coordination of one or four neutral pyrazole ligand(s) in the coordination spheres of technetium generated by thermal decomposition of the pyrazolylborates [TcI(NO)Cl2(PPh3)2(pzH)] (1) and [TcI(NS)Cl(pzHMe2)4]+ (5). Reactions with the corresponding thionitrosylrhenium complex [ReII(NS)Cl3(PPh3)2] require higher temperatures and only compounds with one pyrazole ligand, [ReI(NS)Cl2(PPh3)(pzHR)] (6a-6c), were isolated. The products were studied spectroscopically and by X-ray diffraction.

Solubility, complexation and thermodynamics of the Tc(IV)-isosaccharinic acid system: Trends in the M(IV) series.

Isosaccharinic acid (HISA, or ISA in its deprotonated form) is the main degradation product of cellulose under alkaline conditions. It can form strong complexes with radionuclides and other toxic metal ions, eventually enhancing their mobility in the context of nuclear waste repositories and other environmental systems. 99Tc is a redox-sensitive, long-lived fission product produced in high yield in nuclear reactors. The solubility of 99Tc(IV) was investigated in 0.5 M NaCl‒NaISA‒NaOH solutions with 6 ≤ pHm ≤ 12.5 and 10-6 M ≤ [ISA] ≤ 0.2 M. Complete chemical and thermodynamic models were derived on the basis of solubility data, (pe + pHm) measurements, redox speciation, and solid phase characterization. These models include the previously unreported aqueous complexes TcO(OH)(ISA)2‒ and TcO(OH)2(ISA)22-. In spite of the small size and high polarizability of the Tc4+ metal ion, the Tc(IV)-ISA complexes described in this work are significantly weaker than other ISA complexes formed with larger M4+ metal ions, i.e., Zr, Pu and U. This unexpected behavior can be possibly explained by the strong hydrolysis of Tc(IV) and corresponding stabilization of the TcO2+ moiety, which does not occur for other M(IV) systems. Thermodynamic data derived in this work can be implemented in geochemical calculations of relevance in the context of nuclear waste disposal and other environmental applications.

Comparison of diagnostic value of technetium 99m-labeled red blood cell computed single photon emission computed tomography/computed tomography (99mTc-RBC SPECT/CT) and contrast-enhanced multidetector computed tomography (MDCT) for small bowel bleeding: a retrospective study.

Background: Although small bowel bleeding is relatively rare, it is a potentially fatal disease, and its diagnosis still faces challenges. Technetium 99m-labeled red blood cell computed single photon emission computed tomography/computed tomography (99mTc-RBC SPECT/CT) and contrast-enhanced multidetector computed tomography (MDCT) are common imaging methods for diagnosing small bowel bleeding, but there have been no studies comparing their diagnostic efficacy for this purpose. This study aims to compare the diagnostic value of 99mTc-RBC SPECT/CT and contrast-enhanced MDCT for small bowel bleeding. Methods: A total of 44 patients (30 males and 14 females, median age of 64 years) definitively diagnosed with small bowel bleeding and 15 non-small bowel bleeding patients (8 males and 7 females, median age of 66 years) were consecutively included in this study. All patients underwent 99mTc-RBC SPECT/CT and contrast-enhanced MDCT examinations at Beijing Friendship Hospital of Capital Medical University between January 2020 to September 2023. The definitive diagnosis had been made through surgery or colonoscopy, or through patient history, patient management, and clinical follow-up. We collected clinical data of the participants. 99mTc-RBC SPECT/CT and contrast-enhanced MDCT were reviewed in a blinded fashion for accuracy of detection of active bleeding as well as the active small bowel bleeding location. Results: Among the 59 patients, the accuracy, sensitivity, and specificity of 99mTc-RBC SPECT were 27.3%, 93.3%, and 92.3%; for 99mTc-RBC SPECT/CT they were 76.3%, 40.5%, and 93.3%; whereas for contrast-enhanced MDCT they were 45.8%, 27.3%, and 100%, respectively. The diagnostic accuracy of 99mTc-RBC SPECT/CT for jejunal and ileal bleeding was high, at 100% and 86.4%, respectively. Meanwhile, 99mTc-RBC SPECT/CT had a higher accuracy in diagnosing more causes of small bowel bleeding. In 59 patients, the combination of 99mTc-RBC SPECT/CT and contrast-enhanced MDCT accurately diagnosed small bowel bleeding and provided precise localization in 50 patients, resulting in the accuracy, sensitivity, and specificity of 84.7%, 79.5%, and 100.0%, respectively. Conclusions: 99mTc-RBC SPECT/CT has high diagnostic value in diagnosing small bowel bleeding and is superior to 99mTc-RBC SPECT and contrast-enhanced MDCT. The combination of 99mTc-RBC SPECT/CT and contrast-enhanced MDCT can further improve the diagnostic accuracy of diagnosis, and can accurately guide the diagnosis and treatment of small bowel bleeding.

99mTc-labeled, tofacitinib citrate encapsulated chitosan microspheres loaded in situ gel formulations for intra-articular treatment of rheumatoid arthritis.

Inflammatory diseases including rheumatoid arthritis are major health problems. Although different techniques and drugs are clinically available for the diagnosis and therapy of the disease, novel approaches regarding radiolabeled drug delivery systems are researched. Hence, in the present study, it was aimed to design, prepare, and characterize 99mTc-radiolabeled and tofacitinib citrate-encapsulated microsphere loaded poloxamer in situ gel formulations for the intra-articular treatment. Among nine different microsphere formulations, MS/TOFA-9 was chosen as the most proper one due to particle size, high encapsulation efficiency, and in vitro drug release behavior. Poloxamer 338 at a concentration of 15% was used to prepare in situ gel formulations. For intra-articular administration, microspheres were dispersed in an in situ gel containing 15% Poloxamer 338 and characterized in terms of gelation temperature, viscosity, rheological, mechanical, and spreadability properties. After the determination of the safe dose for MS/TOFA-9 and PLX-MS/TOFA-9 as 40 µL/mL in the cell culture study performed on healthy cells, the high anti-inflammatory effects were due to significant cellular inhibition of fibroblasts. In the radiolabeling studies with 99mTc, the optimum radiolabeling condition was determined as 200 ppm SnCl2 and 0.5 mg ascorbic acid, and both 99mTc-MS/TOFA-9 and 99mTc-PLX-MS/TOFA-9 exhibited high cellular binding capacity. In conclusion, although further in vivo experiments are required, PLX-MS/TOFA-9 was found to be a promising agent for intra-articular injection in rheumatoid arthritis.

99mTc(I)-Labeled His-Tagged Proteins: Impact in the Development of Novel Imaging Probes and in Drug Discovery.

Technetium-99m (99mTc) remains the cornerstone of nuclear medicine for single photon emission computed tomography (SPECT) due to its widespread availability and chemical and physical features. Its multiple oxidation states allow for the design and production of radiopharmaceuticals with versatile properties, namely in terms of pharmacokinetic profile. 99mTc(V) is the most common oxidation state, but 99mTc(I) gained traction after the pioneering work of Alberto and colleagues, which resulted in the introduction of the organometallic core fac-[99mTc(CO)3(H2O)3]+. This core is readily available from [99mTcO4]- and displays three labile water molecules that can be easily swapped for ligands with different denticity and/or donor atoms in aqueous environment. This makes it possible to radiolabel small molecules as well as high molecular weight molecules, such as antibodies or other proteins, while assuring biological activity. Direct radiolabelling of those proteins with fac-[99mTc(CO)3]+ under mild conditions is accomplished through incorporation of a polyhistidine tag (His-tag), a commonly used tag for purification of recombinant proteins. This review aims to address the direct radiolabelling of His-tagged macromolecules with fac-[99mTc(CO)3]+ for development of molecular imaging agents and the impact of this technology in the discovery and development of imaging and/or therapeutic agents towards clinical application.

Alternatives for the Detection and Diagnosis of Osteoarticular Infections: An Exploratory Review.

The precise diagnosis of osteomyelitis, a bone infection, remains a significant challenge for healthcare professionals. This difficulty stems from the highly variable nature of its clinical presentation and disease course. Patients can exhibit a wide range of symptoms, making it easy to misdiagnose the condition. In turn, inaccurate diagnoses lead to inappropriate treatment regimens, potentially hindering a patient's recovery and causing unnecessary complications. Nuclear medicine offers a ray of hope in this fight against diagnostic ambiguity. It provides valuable tools, such as radiopharmaceutical imaging, that can significantly improve the accuracy of osteomyelitis diagnosis. However, limitations exist. This article explores the need for alternative diagnostic approaches within the specific context of Costa Rica. This exploration is particularly relevant due to the current regional shortage of gallium-67 (67Ga), a radiopharmaceutical commonly used in osteomyelitis diagnosis. The article delves into the nature, function, and limitations of various nuclear medicine techniques, encompassing both independent radiopharmaceuticals like 67Ga and those conjugated with specific targeting molecules to pinpoint areas of infection within the body. Given the scarcity of 67Ga in Costa Rica, it becomes crucial to explore and implement viable alternative diagnostic techniques within the healthcare system. This article emphasizes the need for further investigation into these alternatives, with the goal of improving diagnostic accuracy and ensuring optimal patient care. By implementing these alternatives, healthcare professionals in Costa Rica can effectively combat the challenges posed by osteomyelitis and pave the way for better patient outcomes.

Diagnostic efficacy of [99mTc]Tc-PSMA SPECT/CT for prostate cancer: a meta-analysis.

BACKGROUND: Prompt and accurate diagnosis of prostate cancer (PCa) is of paramount importance for effective treatment planning. While Gallium-68 labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has proven efficacy in detecting PCa, limited availability poses challenges. As a potential alternative, [99mTc]Tc-PSMA single photon emission computed tomography (SPECT)/computed tomography (CT) holds promise. This systematic review and meta-analysis aimed to evaluate the diagnostic value of [99mTc]Tc-PSMA SPECT/CT for prostate cancer. METHODS: A comprehensive search of PubMed, Cochrane, EMBASE, Scopus, Ovid, and Web of Science databases was conducted until July 2024. Sensitivity and specificity data were extracted to assess the diagnostic accuracy of [99mTc]Tc-PSMA SPECT/CT, while the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate study quality. Statistical analyses were performed using STATA 18, with MetaDisc 1.4 employed to detect threshold effects. Diagnostic accuracy indicators, including sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (LR-), and positive likelihood ratio (LR+), were pooled. The area under the curve (AUC) of the combined model was calculated using summary receiver-operating characteristic (SROC) curves. RESULTS: Seven studies meeting the inclusion criteria were identified from an initial pool of 1467 articles, with no publication bias observed. The pooled sensitivity, specificity, and AUC of [99mTc]Tc-PSMA SPECT/CT were found to be 0.89 (95% CI, 0.84-0.93), 0.92 (95% CI, 0.67-0.99), and 0.93 (95% CI, 0.90-0.95), respectively. Additionally, the comprehensive diagnostic odds ratio, diagnostic score, positive likelihood ratio, and negative likelihood ratio were calculated as 95.24 (95% CI, 17.30-524.41), 4.56 (95% CI, 2.85-6.26), 11.35 (95% CI, 2.31-55.71), and 0.12 (95% CI, 0.08-0.18), respectively. CONCLUSIONS: In conclusion, our findings demonstrate that [99mTc]Tc-PSMA SPECT/CT exhibits favorable diagnostic performance for prostate cancer and can provide valuable supplementary information, particularly in regions and settings where [68Ga]Ga-PSMA PET/CT availability is limited, such as remote areas. These results highlight the potential of [99mTc]Tc-PSMA SPECT/CT as a valuable tool in the diagnosis and management of prostate cancer, warranting further investigation and validation in larger patient cohorts.

Radiolabeling of bionanomaterials with technetium 99m: current state and future prospects.

Radiolabeling of bionanomaterials with technetium-99m (99mTc) has become a promising approach in combining the benefits of nanotechnology and nuclear medicine for diagnostic and therapeutic purposes. This review is intended to provide a comprehensive overview of the state-of-the-art of radiolabeling of bionanomaterials with 99mTc, highlighting the synthesis methods, labeling mechanisms, biological evaluation, physicochemical characterization and clinical applications of 99mTc-labeled bionanomaterials. Various types of nanomaterials are considered in the review, including lipid- and protein-based nanosystems, dendrimers and polymeric nanomaterials. Moreover, the review assesses the challenges presented by this emerging field, such as stability of the radiolabel, potential toxicity of the nanomaterials and regulatory aspects. Finally, promising future perspectives and areas of research development in 99mTc-labeled bionanomaterials are discussed.

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Novel technetium-99m-labeled bivalent PSMA-targeting probe based on hydroxamamide chelate for diagnosis of prostate cancer.

OBJECTIVE: Prostate-specific membrane antigen (PSMA) is a well-known biomarker of prostate cancer. Previously, our group reported that the succinimidyl-cystatin-urea-glutamate (SCUE) moiety has a high affinity for PSMA. In this study, we developed the novel technetium-99m-labeled PSMA-targeting probe "[99mTc]Tc-(Ham-SCUE)2" based on a hydroxamamide chelate with a bivalent SCUE and evaluated its potential as a SPECT imaging probe for the diagnosis of PSMA-expressing prostate cancer. METHODS: Ham-SCUE was synthesized by a one-step reaction with Ham-Mal and cysteine-urea-glutamine. Then, Ham-SCUE was reacted with [99mTc]NaTcO4 for 10 min at room temperature to obtain [99mTc]Tc-(Ham-SCUE)2. [99mTc]Tc-(Ham-SCUE)2 was added to LNCaP (high PSMA expression) cells or PC3 (low PSMA expression) cells, and their radioactivity was measured 60 min after administration. The blocking study was performed by co-incubation of LNCaP cells with various concentrations of 2-PMPA (a PSMA inhibitor) for 15 min before adding [99mTc]Tc-(Ham-SCUE)2. The biodistribution of [99mTc]Tc-(Ham-SCUE)2 in LNCaP/PC3 dual xenografted C.B.-17/Icr scid/scid Jcl mice was evaluated for 120 min after intravenous injection. The blocking study was performed by pretreatment of mice with 2-PMPA (10 mg/kg weight). RESULTS: [99mTc]Tc-(Ham-SCUE)2 was acquired at radiochemical yields of 56% with a radiochemical purity of over 95%. The cellular uptake level of [99mTc]Tc-(Ham-SCUE)2 by LNCaP cells was significantly higher than that by PC3 cells (LNCaP: 11.12 ± 0.71 vs. PC3: 1.40 ± 0.13%uptake/mg protein, p < 0.01), and the uptake was significantly suppressed by pretreatment with 2-PMPA (2.56 ± 0.37%uptake/mg protein, p < 0.05). IC50 of 2-PMPA was 245 ± 47 nM. In the in vivo study, the radioactivity of LNCaP tumor tissue was significantly higher than that of PC3 tumor tissue at 120 min after the administration of [99mTc]Tc-(Ham-SCUE)2 (LNCaP: 9.97 ± 2.79, PC3: 1.16 ± 0.23%ID/g, p < 0.01), and was suppressed by pretreatment with 2-PMPA (2.50 ± 0.45%ID/g, p < 0.01). CONCLUSION: [99mTc]Tc-(Ham-SCUE)2 has the potential to be a SPECT imaging agent for diagnosing high PSMA-expressing prostate cancer.