Search

[Display omitted] Negatively charged microspheres (NCMs) are postulated as a new form of treatment for chronic wounds. Despite the efficacy shown at clinical level, more studies are required to demonstrate their safety and local effect. The objective of the work was to confirm the lack of NCM systemic absorption performing a biodistribution study of the NCMs in an open wound rat animal model. To this end, radiolabeling of NCMs with technetium-99 m was optimized and biodistribution studies were performed by in vivo SPEC/CT imaging and ex vivo counting during 24 h after topical administration. The studies were performed on animals treated with a single or repeated dose to study the effect of macrophages during a prolonged treatment. NCM radiolabeling was achieved in a simple, efficient and stable manner with high yield. SPECT/CT images showed that almost all NCMs (about 85 %) remained on the wound for 24 h either after single or multiple administrations. Ex vivo biodistribution studies confirmed that there was no accumulation of NCMs in any organ or tissue except in the wound area, suggesting a lack of absorption. In conclusion, NCMs can be considered safe as local wound treatment since they remain at the administration area. [ABSTRACT FROM AUTHOR]

[Display omitted] Lung cancer (LC) is a common type of cancer, which is a leading cause of death around the world. There is an urgency for the development of new drugs that could diagnose the LC in the early stages and in a precise manner. In this direction, the development of nanoparticles radiolabeled with the diagnostic radioisotopes represent an important advance in the field of cancer imaging. In this study were developed PLA/PVA/Atezolizumab nanoparticles which were radiolabeled with 99mTc (Technetium-99m). The radiolabeled nanoparticles were evaluated in both: in-vitro (L-929 and A-549) as in-vivo (mice). The results showed no cytotoxicity effect in the healthy cells (L-929) and cytotoxicity effect in the tumor cells (A-549). The biodistribution assay demonstrated that 99mTc-PLA/PVA/Atezolizumab could reach the tumor site 14-folds higher than the nonparticulate atezolizumab. In conclusion, 99mTc-PLA/PVA/Atezolizumab nanoparticles showed to be a new drug which is able to precisely image the lung tumor, and it must be considered for clinical trials. [ABSTRACT FROM AUTHOR]

[Display omitted] Edelfosine (ET) is a potent antitumor agent but causes severe side effects that have limited its use in clinical practice. For this reason, nanoencapsulation in lipid nanoparticles (LNs) is advantageous as it protects from ET side-effects. Interestingly, previous studies showed the efficacy of LNs containing ET in various types of tumor. In this paper, biodistribution studies of nanoencapsulated ET, administered by three routes (oral, intravenous (IV) and intraperitoneal (IP)), were tested in order to select the optimal route of administration. To do this, ET-LNs were labeled with Technetium-99 m (99mTc) and administered by the oral, IV and IP route in mice. IV administration of the radiolabeled LNs led to fast elimination from the blood circulation and increased accumulation in reticulo-endothelial (RES) organs, while their oral administration could not provide any evidence on their biodistribution since large radiocomplexes were formed in the presence of gastrointestinal fluids. However, when the LNs were administered by the IP route they could access the systemic circulation and provided more constant blood ET-LN levels compared to the IV route. These findings suggest that the IP route can be used to sustain the level of drug in the blood and avoid accumulation in RES organs. [ABSTRACT FROM AUTHOR]

With the goal of developing theranostic agents for application in radiopharmaceutical chemistry, in this work, we studied p -NCS-Bn-NODAGA (1) as a bifunctional chelator for the fac -[M(CO) 3 ]+ core (M = natRe, 186Re, 99mTc). Specifically, we studied complexes of the formula [M(CO) 3 (L)]+, where L denotes either Bn-NODAGA-Pyr (2) or Bn-NODAGA-Ser-Ser-RM2 (3). The model bioconjugate molecule 2 was synthesized by conjugating pyrrolidine with 1 , while 3 was derived from the conjugation of the gastrin-releasing peptide receptor (GRPR)-targeting peptide Ser-Ser-RM2 with 1. Labeling of 2 and 3 was performed with [M(CO) 3 (OH 2) 3 ]+ (where M = natRe, 186Re, or 99mTc). The stability of the radioactive complexes was studied against l -histidine and l -cysteine (1 mM in PBS; pH 7.4, 37 °C). GRPR affinity of both peptide 3 and its metallated counterpart, Re-3 , were determined with in vitro competitive binding assays in GRPR-expressing PC-3 cells using [125I]I-Tyr4-BBN as the competitor. After a thorough radiolabeling optimization process, the [M(CO) 3 (2)]+ model complexes (M = 186Re and 99mTc) were synthesized with 94 ± 2% radiochemical yield (RCY; estimated by radio-HPLC). In stability studies, [ 186 Re]Re-2 remained intact through 7 d in l -cysteine and l -histidine. Similarly, stability studies in rat serum at 37 °C showed 99 ± 1% intact [ 186 Re]Re-2 through 4 h. Non-specific rat serum protein binding of [ 186 Re]Re-2 was found to be 33 ± 4% at 4 h. The [ 99m Tc]Tc-2 complex was found to be stable in l -histidine and l -cysteine at 37 °C through 24 h. [ 99m Tc]Tc-2 was also stable in rat serum, with 38 ± 3% non-specific protein binding, at 4 h. The [M(CO) 3 (3)]+ peptide radiometal complex (M = 186Re and 99mTc) syntheses were also optimized, resulting in RCYs of 35% for [ 186 Re]Re-3 and 47% for [ 99m Tc]Tc-3 (estimated by radio-HPLC). [ 186 Re]Re-3 showed 98 ± 2% and 84 ± 5% stability in l -histidine and l -cysteine, respectively, through 48 h. Similarly, stability studies in rat serum at 37 °C showed 85 ± 3% intact [ 186 Re]Re-3 through 4 h, with 29 ± 7% non-specific protein binding in rat serum. [ 99m Tc]Tc-3 was found to be 84 ± 3% and 82 ± 4% stable in l -histidine and l -cysteine at 24 h, respectively. [ 99m Tc]Tc-3 in rat serum at 37 °C showed 88 ± 2% stability through 4 h, with 25 ± 2% non-specific protein binding. Both 3 and Re-3 demonstrated high GRPR affinity, with IC 50 values of 3.1 nM and 3.9 nM, respectively. The low nanomolar IC 50 values obtained for 3 and Re-3 demonstrate high affinity of this novel [M(CO) 3 ]-labeled bioconjugate for GRPR. The encouraging stability studies and receptor affinity results demonstrate promise for further development of these metal complexes as a theranostic matched pair for targeting GRPR. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • fac -[M(CO) 3 L2L1] (M = Re, 99mTc) mixed ligand complexes with bioactive ligands. • Curcumin as bidentate L2 ligand, 2-phenylbenzothiazole isonitrile as monodentate L1. • Two important pharmacophores combine for the first time in one novel structure. • Anticancer synergy anticipated due to presence of two anticancer pharmacophores. The synthesis and characterization of neutral [2 + 1] tricarbonyl mixed-ligand ReI- and 99mTcI-complexes of the general formula fac -[Re/99mTc(CO) 3 (OO)(isc)] is reported herein. The complexes bear acetylacetone (acac) or curcumin (curc) as monoanionic bidentate (OO) ligands and isocyanide (isc) derivatives of the anticancer agent 2-(4′-aminophenyl)benzothiazole (1) and its 3́-methyl-substituted counterpart (2) as monodentate ligands. The Re complexes were synthesized through the addition of 1 and 2 , efficiently prepared in four steps, to the aqua intermediate fac -[Re/99mTc(CO) 3 (OO)(H 2 O)], formed by the reaction of the [Et 4 N] 2 [Re(CO) 3 Br 3 ] precursor with the OO bidentate ligands. Ligands 1 and 2 and the corresponding complexes 3-Re and 4-Re (OO acetylacetone), as well as 5-Re and 6-Re (OO curcumin), were fully characterized by elemental analysis, ESI-MS analysis, IR, and NMR. X-ray crystallographic analysis of 3-Re showed that it crystallizes in the monoclinic centrosymmetric space group C 2/ c with two crystallographically independent molecules in the asymmetric unit that form a dimer through intermolecular π–π stacking interactions between the aromatic rings of the ligand. Synthesis was subsequently transferred at 99mTc-tracer level using the fac -[99mTc(CO) 3 (H 2 O) 3 ]+ precursor and the corresponding 3-99mTc–6-99mTc complexes were prepared with a radiochemical yield of >92% and characterized by comparative HPLC analysis using the well-characterized Re complexes as reference. All 99mTc-complexes show good stability against the histidine and cysteine challenge, while their lipophilicity logD 7.4 values of 2.55–2.78 fulfil the requisite for high bioavailability. The complexes synthesized bear important pharmacophores, which in complexes 5 and 6 co-exist in the same molecule, representing unique structures currently evaluated for anticancer activity. [ABSTRACT FROM AUTHOR]

Serotonergic (5-hydroxytryptamine; 5-HT) receptors play critical roles in neurological and psychological disorders such as schizophrenia, anxiety, depression, and Alzheimer's diseases. Therefore, it is particularly important to develop novel radioligands or modify the existing ones to identify the serotonergic receptors involved in psychiatric disorders. Among the 16 subtypes of serotonergic systems, only technetium-99m based radiopharmaceuticals have been evaluated for serotonin-1A (5-HT 1A), serotonin-2A (5-HT 2A), 5-HT 1A/7 heterodimers and serotonin receptor neurotransmitter (SERT). This review focuses on recent efforts in the design, synthesis and evaluation of 99mTc-radioligands used for single photon emission computerized tomography (SPECT) imaging of serotonergic (5-HT) receptors. Additionally, the discussion will cover aspects such as chemical structure, in vitro / vivo stability, affinity toward serotonin receptors, blood-brain barrier permeation (BBB), and biodistribution study. [Display omitted] • Based on the structure and function of serotonin receptors have been divided into seven families (5-HT 1−7). • Serotonergic receptors have critical roles in neurological and psychological disorders. • Review of design, synthesis, and evaluation of 99mTc-labeled probes synthesized for serotonergic receptor imaging. [ABSTRACT FROM AUTHOR]

[Display omitted] • New C-3 fluoroquinolones derivatives and their [99mTc/Re(CO) 3 ] complexes. • 99mTc-complexes were tested in E. coli bacteria and in E. coli infected mice. • 99mTc-complexes were tested in CT26 tumor cells and in tumor-bearing mice. Fluoroquinolones (FQ) are clinically used antibacterial agents. Antibacterial fluoroquinolone derivatives have been shown to exhibit cytotoxic properties in tumor cells. In this work, C3-carboxy fluoroquinolones derivatives were radiolabeled with the diagnostic radionuclide technetium-99 m and were evaluated as infection- and tumor-targeted agents. First, ciprofloxacin and enrofloxacin were converted to 3-hydrazides and then to the respective pyridine hydrazones (L1 and L2). Secondly, 3-carboxamide of enrofloxacin was converted to dipicolylamine (L3), and picolylaminoacetate (L4) tridentate chelators. The respective rhenium-tricarbonyl complexes of L1-L4 were synthesized and characterized by spectroscopic methods and were used as non-radioactive standards to characterize the analogous 99mTc-radiotracers. The 99mTc-tricarbonyl complexes were synthesized and their lipophilicity and stability were evaluated in vitro. The most stable tracers 99mTcL3, 99mTcL4, were incubated with E. coli cells and CT-26 murine colon adenocarcinoma cells to assess their cellular uptake. Also, the 99mTc-tracers were injected in mice, infected with E. coli, as well as in mice, bearing CT-26 tumors. [ABSTRACT FROM AUTHOR]

With the long-term goal of developing a diagnostic (99mTc) and therapeutic (186Re) agent pair for targeting somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs), we developed novel metal-cyclized peptides through direct labeling of the potent SSTR2 antagonist Ac-4-NO 2 -Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH 2 (1) with Re (in Re- 1), 99mTc (in [99mTc]Tc- 1) and 186Re (in [186Re]Re- 1). Re- 1 was characterized by LC-ESI-MS and HR-ESI-MS and was tested for receptor affinity in SSTR-expressing cells (AR42J). Radiolabeling of the peptide was achieved via ligand exchange from 99mTc-labeled glucoheptonate or [186Re]ReOCl 3 (PPh 3) 2 , yielding [99mTc]Tc- 1 or [186Re]Re- 1 , respectively. In vitro stability of [99mTc]Tc- 1 /[186Re]Re- 1 in PBS (10 mM) at pH 7.4 and 37 °C was determined by HPLC analysis. Moreover, [99mTc]Tc- 1 stability was tested in cysteine (1 mM) and rat serum under the same conditions. Re- 1 consisted of two isomers, confirmed by LC-ESI-MS, with good SSTR2 affinity (IC 50 = 43 ± 6 nM). Optimization of the 99mTc labeling through varying reaction parameters such as pH, reaction time, and Sn2+ and ligand concentrations resulted in high radiochemical yield (RCY ≥92%). Similarly, [186Re]Re- 1 was prepared in reasonable RCY (≥50%). Both 99mTc/186Re-tracers consisted of two product isomers as identified by HPLC co-injection with Re- 1. While [99mTc]Tc- 1 was sufficiently stable in vitro (≥71% intact through 4 h in PBS, cysteine and rat serum), [186Re]Re- 1 exhibited more moderate in vitro stability (58% intact after 1 h in PBS). Novel 99mTc/186 Re -cyclized SSTR2 antagonist peptides were synthesized and characterized using the Re-cyclized analogue as a reference. Due to the nanomolar SSTR2 affinity of Re- 1 and good in vitro stability of [99mTc]Tc- 1 , the latter shows early promise for development as a radiodiagnostic agent for SSTR-expressing NETs. The 99mTc-cyclized complex showed promising in vitro properties, and future in vivo studies will determine the potential for translating such a design into the human clinic. [Display omitted] [ABSTRACT FROM AUTHOR]

The identification of sentinel lymph nodes (SLNs) is important in deciding the resection range during surgery. 99mTc-labeled mannosylated human serum albumin (99mTc]Tc-MSA) is a radiopharmaceutical developed for SLN detection by targeting macrophages. Evans blue (EB) is a blue dye binding strongly to albumin and has been used for SLN detection. 99mTc]Tc-MSA-EB conjugate was prepared as a multi-modal imaging agent and tested its performance by visual investigation, fluorescence imaging and SPECT/CT for SLN mapping in mice. EB was mixed with various concentration of MSA to prepare MSA-EB conjugates. The binding efficiencies were determined using thin-layer chromatography. The UV-VIS spectra and molar extinction coefficient of the conjugate were obtained. The fluorescence was monitored at the excitation wavelength range 420–780 nm and the emission wavelength range 520–845 nm. The 99mTc]Tc-MSA-EB conjugate and EB were injected into the footpads of normal BALB/c mice to check the lymph node (LN) uptakes. The visible, fluorescence, and SPECT/CT images were obtained after injection. The conjugation of EB with MSA increased by time and was saturated within 10 min. The molar extinction coefficient of the conjugate was 99,259.3/M/cm at 620 nm. The uptake of conjugate into the popliteal LN after injection into the footpads of mice was investigated visually and fluorescence imaging. SPECT/CT images showed that the standardized uptake values of 99mTc]Tc-MSA-EB conjugate in popliteal LN were about 4 times higher than in sciatic LN at all timepoints. It was confirmed by investigating resected LN that the blue color, fluorescence, and radioactivity of the 99mTc]Tc-MSA-EB conjugate were retained only on the LN and did not spread to adjoining tissues. 99mTc]Tc-MSA-EB conjugate has a great potential as a multi-modal SLN mapping agent which could be detected by visual investigation, fluorescence imaging, and SPECT/CT. [ABSTRACT FROM AUTHOR]

Cellulose nanocrystals (CNCs) are known as nano-biomaterials that can be achieved from the different sources. The designated CNCs have been successfully fabricated from the roots of Dorema kopetdaghens (Dk) plant by sulphuric acid hydrolysis method. Structural analysis has been carried out by the means of XRD, FTIR, and TGA/DTG procedures. The XRD results have indicated that the crystalline structure of CNCs had been cellulose I with the crystallinity index of 83.20% and size of 4.95 nm. The FTIR spectra have shown that the resulting samples have been related to the cellulose species. The thermal properties of CNCs have exhibited a lower thermal stability in comparison to the untreated roots. It has been indicated by the morphological analyses of FESEM, TEM, and AFM that the nanoparticles had contained a spherical shape. Also, the cytotoxicity of CNCs against A549 cell line has not exhibited any cytotoxic effects. The analysis of labeling efficiency in regards to 99mTc-CNCs has been observed to be above 98%, while the biodistribution of radioactivity has displayed a high uptake by the kidneys and blood circulation. Therefore, it is possible to transform the low-cost by-product into a beneficial substance such as CNCs that can be utilized in bioimaging applications. Unlabelled Image • The production of CNCs from Dorema kopetdaghens plant by acid hydrolysis • CNCs have not caused any significant cellular toxicity effects on the A549 cells. • The direct labeling of CNCs by Tc-99m for diagnostic and bioimaging applications • Labeling efficiency of 99mTc-CNCs was >98%. • The biodistribution of radioactivity has displayed a high uptake by the kidneys. [ABSTRACT FROM AUTHOR]

This study presents the synthesis and characterization of chitosan-glutamine-based biocompatible nanoparticles (nano-conjugate) as a platform for developing an efficient nano-radiopharmaceutical agent for liver imaging. The nanoparticles were labeled with technetium-99 m, resulting in the formation of 99mTc-chitosan-glutamine. Various characterization techniques, including furrier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H NMR) were performed for confirmation of synthesized nano-conjugate. Scanning electron microscopy (SEM), dynamic light scattering (DLS), and static light scattering (SLS) spectroscopies were employed to investigate the particle properties such as size, zeta potential, and molecular weight. MTT assay was conducted to study the toxicity of chitosan-glutamine showing that nano-conjugate had a toxicity on cancer cell in-vitro. In-vivo studies were conducted by administering 99mTc-chitosan-glutamine to mice, followed by whole body SPECT imaging. The imaging process was performed at three different time points post-injection: 15, 60, and 120 min. The SPECT results revealed a significantly accumulation in the liver. Also, biodistribution study showed that accumulation in liver (% ID/g = 23.15%) was significantly higher than other organs. Our in-vitro and in-vivo findings suggest that 99mTc-chitosan-glutamine could serve as a theranostic agent for cancer imaging using SPECT technology. [ABSTRACT FROM AUTHOR]

Brain abscess is a life-threatening condition that requires a timely and accurate diagnosis. In this study, linezolid, an oxazolidinone antibiotic, was labeled with technetium-99m according to the stannous chloride method. The labeling reaction factors were studied and optimized to achieve a high yield (97.4 ± 2.3%). The 99mTc-linezolid was radio- and physico-chemically characterized to assess its suitability as a radiopharmaceutical for the brain. In-silico docking to target peptidyltransferase showed an optimal binding fit (energy = −66.6 Kcal/mol). The complex was biologically evaluated in-vitro using binding assays in alive and heat-killed bacteria and in-vivo in an MRSA brain infection model. All results suggested that the labeled complex could potentially be a new nuclear imaging agent to diagnose and localize brain abscesses specifically. • Factors affecting the labeling yield of linezolid with technetium-99m were studied and optimized. • At optimized labeling conditions, 99mTc-linezolid was obtained at a high radiochemical yield (∼97.4%) and good stability (<24h). • The selectivity of 99mTc-Linezolid to target the bacterial peptidyltranferase was confirmed using in-silico and in vitro binding studies. • Animal models showed that 99mTc-linezolid could cross the blood-brain barrier and tend to accumulate in bacterial brain abscesses. • The reported data encouraged further assessment of the labeled linezolid to diagnose and localize brain abscesses. [ABSTRACT FROM AUTHOR]

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (99mTc) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent α4β2-nAChR agonist, we prepared A85380 derivatives labeled with 99mTc using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a 99mTc analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at α4β2-nAChR in both the docking simulation (−19.3 kcal/mol) and binding assay (Ki = 0.4 ± 0.04 nM). Further, 99mTc-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that 99mTc-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy. [ABSTRACT FROM AUTHOR]

99mTc-conjugated anti-program death1 (anti-PD-1) JS001 antibody, as a novel radionuclide-based imaging agent, was developed for noninvasively detecting PD-1 expression in both S180 sarcoma xenografts and gastric cancer BGC823 orthotopic nude mice. The in vivo SPECT imaging of 99mTc-JS001 showed high uptake in kidney, liver, blood pool and tumor at 28 h post injection. There was a higher uptake in the BGC823 orthotopic tumor than that in the adjunct stomach. These results demonstrated that 99mTc-JS001 can be used to monitor the pharmacological profiles of anti-PD-1 antibody, and may have potential to screen patients for PD-1 immuono-therapy. Here we reported the development of a novel immuno-SPECT tracer, namely 99mTc-JS001, to non-invasively image PD-1 expression in mice. The JS001 antibody was directly labeled by the most widely used SPECT radionuclide 99mTc with a radiochemical yield of 90%, and the specific activity was ≤74 GBq/mmol. After the radiolabeling, 99mTc-JS001 exhibited a similar immnuoaffinity to PD-1 in vitro. 99mTc-conjugated JS001 maintained intact in 5% HSA system for 24 h. S180 sarcoma xenograft-bearing Kunming mice and BGC823 gastric cancer orthotopic tumor model were built. Bio-distribution and/or immuno-SPECT studies with 99mTc-JS001 showed the antibody maintained in the blood, liver, kidneys and tumors at 1.5 ID%/g, 1.4 ID%/g, 2.0 ID%/g and 0.5 ID%/g, respectively. Also, there was a higher uptake in the BGC823 orthotopic tumor than that in the adjunct stomach. These results demonstrated that 99mTc-JS001 might have capacity to monitor the PD-1 expression in vivo, which might facilitate the anti-PD-1 antibodies treatment in preclinical models. [ABSTRACT FROM AUTHOR]

During the last four decades, nuclear medicine has undergone enormous growth, and positron emission tomography (PET) has been in the driving seat for most of the time. 18F-fluorodeoxyglucose (18F-FDG) is the most widely used agent for the detection of hibernating myocardium and metabolically active cancer tissue. But its cost and limited availability are the main limitations. For a long time different researchers and groups of pharmacists have tried to label glucose with a cheaper and long-acting radionuclide like 99mTc. However, they failed to achieve this goal owing to the chemical complexity of 99mTc and the lack of maintaining the physiological activity of diagnostic compounds. A pre-targeting strategy based on strain-promoted [3 + 2] azide-alkyne cycloaddition (SPAAC) reaction was applied to solve this problem. Functional click synthons were synthesized: 2-azido-2-deoxy- d -glucose (GlucN 3) as a glucose analogue, and N- (2- (2- (2- (bis (pyridin-2-ylmethyl) amino) ethoxy) ethoxy) ethyl-2- (6H-11,12-didehydrodibenzo [a,e] cycloocten-5-ylideneaminooxy) acetamide (C7) as a 99mTc(CO) 3 labeling and azido-binding group. The results of biodistribution experiments in mice bearing S180 tumor show the relatively high tumor/blood ratio (up to 2.95) and tumor/muscle ratio (up to 6.37), and both of them decreases significantly in the glucose blocking experiment. It indicates that GlucN 3 behaves similarly to glucose and that in vivo SPAAC reactions can occur effectively. It is supposed that this pre-targeting strategy can indeed enhance target specificity and may be used for glucose metabolism imaging in tumor diagnosis. [ABSTRACT FROM AUTHOR]

Constructed wetlands (CWs) are used for the treatment of wastewater by natural processes. Knowledge of the flow dynamics of wastewater through the CWs is required to evaluate their performance, operation and design. The residence time distribution (RTD) approach was used to evaluate the above-mentioned parameters in a CW. The RTD of wastewater flowing through a pilot-scale CW was measured using Technetium-99 m (99mTc) as a radiotracer. The measured data were analyzed, and mean residence time and stagnant volumes were quantified under different operating conditions. A plug flow component in series along with a tank-in-series model with an exchange between the active and dead zones was used to simulate the measured RTD curves and investigate the flow dynamics of the flowing wastewater. The results of the study showed that the optimum flow rate and wastewater level in the CW was 2.3 m3/s and 0.6 m, respectively. Moreover, the results of the study will help in the operation and design of the existing wetland and design of new wetlands. • RTD measurements were carried out in a CW using the radiotracer technique. • Technetium-99 m as sodium pertechnetate was used as the radiotracer. • Flow fractions across different transacts of the wetland were estimated. • Mean residence time, dead volume, and hydraulic efficiency were quantified. • A model was conceptualized and used to simulate the experimental data. [ABSTRACT FROM AUTHOR]

El cáncer de mama es un problema de salud en todo el mundo, con altas tasas de incidencia y mortalidad. Es bien sabido que el desarrollo de métodos de diagnóstico más sensibles y específicos es de gran importancia, ya que un diagnóstico precoz es esencial para tratar con éxito los tumores. Lapachol es un compuesto natural, perteneciente al grupo de la naftoquinona, que se ha utilizado ampliamente en la medicina tradicional para tratar diversas enfermedades, incluido el cáncer. El objetivo de este estudio fue evaluar el lapachol marcado con tecnecio 99m (99mTc) como una sonda de imágenes para la identificación del cáncer de mama. Para lograr este propósito, el lapachol se marcó con 99mTc, se determinó la pureza radioquímica y la estabilidad in vitro. También se evaluó el aclaramiento en sangre en ratones sanos y la biodistribución en ratones con tumor 4T1. Lapachol fue exitosamente marcado con 99mTc, con altos valores de rendimiento radioquímico (95,9 ± 3,4%). La estabilidad in vitro mostró que el complejo radiomarcado permaneció estable hasta 24 h, con valores superiores al 90% tanto para solución salina como para plasma (95,6 ± 3,6% y 96,4 ± 1,7%, respectivamente). El complejo radiomarcado decae de forma bifásica, con una vida media de distribución y eliminación igual a 3,3 y 50,0 min, respectivamente. La biodistribución y las imágenes gammagráficas mostraron una alta captación en los órganos de excreción (riñones, hígado e intestino). También se puede observar que la captación tumoral fue mayor que en el músculo en todos los puntos temporales. La relación de tumor/músculo alcanza ∼4,5 a las 24 h después de la administración. Estos hallazgos indican que 99mTc-lapachol puede ser un potencial agente de diagnóstico para los tumores de mama. Breast cancer is a health problem worldwide with high incidence and mortality rates. It is well known that the development of more sensitive and specific diagnostic methods is of great importance since an early diagnosis is essential to successfully treat tumors. Lapachol is a natural compound, belonging to the naphthoquinone group that has been widely used in traditional medicine to treat various illnesses, including cancer. The aim of this study was to evaluate technetium-99m (99mTc) labeled lapachol as an imaging probe for breast cancer identification. To achieve this purpose, lapachol was labeled with 99mTc, radiochemical purity and in vitro stability were determined. Blood clearance, in healthy mice, and biodistribution, in 4T1 tumor-bearing mice, were also evaluated. Lapachol was successfully labeled with 99mTc, with high values of radiochemical yield (95.9 ± 3.4%). In vitro stability showed that the radiolabeled complex remained stable for up to 24 h, with values above 90% for both saline and plasma (95.6 ± 3.6% and 96.4 ± 1.7%, respectively). The radiolabeled complex decays in a biphasic manner, with a half-life of distribution and elimination equal to 3.3 and 50.0 min, respectively. Biodistribution and scintigraphic images showed high uptake in organs of excretion (kidneys, liver, and intestine). It could be also noted that tumor uptake was higher than the muscle at all time points. Tumor-to-muscle ratio reaches ∼4.5 at 24 h after administration. These findings suggest that 99mTc-lapachol can be a potential diagnostic agent for breast tumors. [ABSTRACT FROM AUTHOR]

The aim of this work was to develop diagnostic (99mTc) and therapeutic (186Re) agents for targeting somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). In this regard, we evaluated in vitro complexes of the general formula [M(CO) 3 (L-sst 2 -ANT)] (M = 99mTc, 186Re), where L denotes NODAGA or NOTA and sst 2 -ANT denotes the potent SSTR2 antagonist 4-NO 2 -Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH 2. Moreover, we assessed the in vivo properties of the 99mTc-complexes in an animal SSTR-tumor model. The [99mTc]/[186Re][Tc/Re(OH 2) 3 (CO) 3 ]+ precursors were utilized to prepare the 99mTc/186Re-complexes, which were identified by HPLC co-injection with their natRe analogues. The tracers were challenged in vitro at 37 °C against cysteine and histidine in phosphate-buffered saline (pH 7.4) and in rat serum. Biodistribution and micro-SPECT/CT imaging studies of the 99mTc-tracers were performed in AR42J tumor-bearing female ICR SCID mice. The 99mTc-complexes were prepared in high radiochemical yield (RCY > 90%, by HPLC), with lower RCY (≤30%) obtained for 186Re-complexes. Tracers remained intact in vitro and displayed low non-specific binding (10–25%) to rat serum proteins. Biodistribution of [99mTc]Tc-NODAGA-sst 2 -ANT revealed low tumor uptake (2.78 ± 0.27 %ID/g) at 1 h, while high tumor uptake (16.70 ± 3.32 %ID/g) was found for [99mTc]Tc-NOTA-sst 2 -ANT. Moderate to low tumor retention was observed for both tracers after 4 and 24 h. Tumor uptake for [99mTc]Tc-NOTA-sst 2 -ANT was receptor-mediated, as demonstrated by parallel SSTR blocking studies. Rapid renal clearance was observed for both tracers, and SPECT/CT images clearly delineated the tumors, in agreement with the biodistribution data. The [99mTc]Tc-NOTA-sst 2 -ANT complex demonstrated high tumor uptake and rapid clearance in a SSTR-tumor mouse model, showing potential for further development. Preclinical data support the feasibility of the [99mTc]Tc/[186Re]Re-NOTA/NODAGA labeling strategy for use in the development of theranostic radiopharmaceuticals for translation into the human clinic for targeting of SSTR-expressing NETs. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The somatostatin receptor subtype 2 (SSTR2) is often highly expressed on neuroendocrine tumors (NETs), making it a popular in vivo target for diagnostic and therapeutic approaches aimed toward management of NETs. In this work, an antagonist peptide (sst 2 -ANT) with high affinity for SSTR2 was modified at the N -terminus with a novel [N,S,O] bifunctional chelator (2) designed for tridentate chelation of rhenium(I) and technetium(I) tricarbonyl cores, [Re(CO) 3 ]+ and [99mTc][Tc(CO) 3 ]+. The chelator-peptide conjugation was performed via a Cu(I)-assisted click reaction of the alkyne-bearing chelator (2) with an azide-functionalized sst 2 -ANT peptide (3), to yield NSO-sst 2 -ANT (4). Two synthetic methods were used to prepare Re- 4 at the macroscopic scale, which differed based on the relative timing of the click conjugation to the [Re(CO) 3 ]+ complexation by 2. The resulting products demonstrated the expected molecular mass and nanomolar in vitro SSTR2 affinity (IC 50 values under 30 nM, AR42J cells, [125I]iodo-Tyr11-somatostatin-14 radioligand standard). However, a difference in their HPLC retention times suggested a difference in metal coordination modes, which was attributed to a competing N -triazole donor ligand formed during click conjugation. Surprisingly, the radiotracer scale reaction of [99mTc][Tc(OH 2) 3 (CO) 3 ]+ (99mTc; t ½ = 6 h, 141 keV γ) with 4 formed a third product, distinct from the Re analogues, making this one of the unusual cases in which Re and Tc chemistries are not well matched. Nevertheless, the [99mTc]Tc- 4 product demonstrated excellent in vitro stability to challenges by cysteine and histidine (≥98% intact through 24 h), along with 75% stability in mouse serum through 4 h. In vivo biodistribution and microSPECT/CT imaging studies performed in AR42J tumor-bearing mice revealed improved clearance of this radiotracer in comparison to a similar [99mTc][Tc(CO) 3 ]-labeled sst 2 -ANT derivative previously studied. Yet despite having adequate tumor uptake at 1 h (4.9% ID/g), tumor uptake was not blocked by co-administration of a receptor-saturating dose of SS-14. Aimed toward realignment of the Re and Tc product structures, future efforts should include distancing the alkyne group from the intended donor atoms of the chelator, to reduce the coordination options available to the [M(CO) 3 ]+ core (M = Re, 99mTc) by disfavoring involvement of the N -triazole. [ABSTRACT FROM AUTHOR]

Abstract Aims The in vivo targeted diagnostic applications of biosynthetic Cerium oxide nanoparticles (CeO 2 -NPs), prepared by applying chitosan as a stabilizer, was explored by evaluating the cytotoxicity through MTT assay on WEHI 164 cell line, the Hemolytic activity of CeO 2 -NPs and biodistribution in rats. Main methods The CeO 2 -NPs were characterized through the use of TGA/DTG, PXRD, FESEM, FTIR, and UV–Vis spectroscopy. The biodistribution of CeO 2 -NPs were determined by directly labeled nanoparticles with Technetium-99 m (99mTc) radioisotope (99mTc-CeO 2 -NPs). The labeling efficiency and stability of 99mTc-CeO 2 -NPs were also measured with Instant Thin Layer Chromatography (ITLC) method. The saturation study was investigated by 1 mCi of 99mTc-CeO 2 -NPs using different concentrations of WEHI 164 cells after 4 h of incubation. In vivo biodistribution study was performed by intravenous injection of 600 μCi/200 μL 99mTc-CeO 2 -NPs through rat's tail. Key findings CeO 2 -NPs seemed to have a low cytotoxic effect on WEHI 164 cell line and did not result in hemolysis. The biodistribution of CeO 2 -NPs has shown that a huge amount of 99mTc-CeO 2 -NPs was amassed in the living human organs, including liver, lung, spleen, stomach, and thyroid which shows the in vivo stability of the labeled conjugate. Herein, we have developed a facile, economical, and greener synthetic procedure applying Chitosan template. This green approach is comparable to conventional methods that utilize hazardous materials which are would be a suitable alternative to circumvent synthetic issues related to these materials. Significance The bio-applications of nano-sized CeO 2 -NPs were explored to find new horizon to use nanotechnology as the diagnostic tool. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

In this study, the commercially available secnidazole was successfully converted to secnidazole xanthate (SNXT), in which the xanthate group can act as a bifunctional chelator to coordinate with 99m Tc. 99m Tc-nitrido complex of SNXT( 99m TcN-SNXT) and 99m Tc-oxo complex of SNXT( 99m TcO-SNXT) were prepared with high radiochemical purity. Both of the complexes were found to be stable in vitro and to exhibit similar hydrophilicity. In addition, comparative in vitro cell uptake studies under anoxic and normoxic conditions demonstrated that both agents were preferentially taken up by hypoxic cells. Biodistribution studies in mice bearing S180 tumor showed 99m TcO-SNXT exhibited a higher tumor uptake and tumor-to-muscle ratio than 99m TcN-SNXT. Furthermore, in SPECT imaging study, 99m TcO-SNXT exhibited a clear accumulation in tumor at 2 h post-injection, suggesting its potential to be a novel hypoxia imaging agent. [ABSTRACT FROM AUTHOR]

• A theoretical formula for technetium-selective adsorbents was derived. • Experimental validation using activated carbon-based 99mTc generators. • A generalized treatment of Tc-selective chromatographic 99mTc generators. • Quantitative analysis of low specific activity molybdenum-99 compatibility. • 99mTc supply capacity retrospectively estimated using the developed formula. Technetium-99m generators employing a technetium-selective stationary phase are a chromatographic instrument developed for use with 99Mo having low specific activity (LSA); particularly, 99Mo produced by electron accelerators. This paper presents a mathematical description of technetium-selective chromatographic (TSC) 99mTc separation and analyzes its compatibility with LSA 99Mo. We developed a theoretical formula for TSC 99mTc separation by discretizing its pertechnetate selectivity, and validated it using an electron linear accelerator and activated carbon-based TSC (AC-TSC) 99mTc generators. We confirmed that the activity concentration of 99mTc obtained from a TSC 99mTc generator can be calculated directly from its input 99Mo activity regardless of the 99Mo specific activity. The formula corroborates that TSC 99mTc separation is compatible with LSA 99Mo, and has a practical application in estimating the number of TSC 99mTc generators required for 99mTc demand of interest. [ABSTRACT FROM AUTHOR]

The development of new drugs that can specifically screen tumors is a global need. When it comes to lung cancer, which is the second main cause of cancer-related deaths, early detection of lung tumors using appropriate imaging is very important. In this study, gemcitabine hydrochloride (GCH) was radiolabeled with [99mTc]Tc under different conditions (changing reducing agent, antioxidant agent, incubation time, pH, [99mTc]Tc activity) and radiolabeling activity (quality control) using Radio Thin Layer Chromatography and paper electrophoresis. The results showed that the most stable complex ([99mTc]Tc-GCH) was prepared using 0.015 mg of stannous chloride as a reducing agent, 0.01 mg of ascorbic acid as an antioxidant and 37 MBq activity at pH 7.4 after 15 min of incubation time. The complex remained stable for 6 h. Cell incorporation studies showed a six-fold higher uptake of [99mTc]Tc-GCH in cancer (A-549) cells (38.42 ± 1.53) than healthy (L-929) cells (6.11 ± 0.17) have shown that it can. In addition, the different behaviors of R/H-[99mTc]Tc confirmed the specificity of this newly developed radiopharmaceutical. Although these studies are preliminary, it has been concluded that [99mTc]Tc-GCH may be a candidate drug for use in nuclear medicine, particularly in the diagnosis of lung cancer. [Display omitted] • [99mTc]Tc-gemcitabine hydrochloride (GCH) was produced. • Varying reducing agent, antioxidant agent, incubation time, pH, and activity of [99mTc]Tc was optimized. • Quality control studies: Radio Thin Layer Chromatography and paper electrophoresis. • [99mTc]Tc-GCH was able to bind the cancer cells higher than healthy cells corroborating the specificity of the GCH. [ABSTRACT FROM AUTHOR]

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [ 99m Tc][TcO 4 ] - ubiquitously employed for the production of 99m Tc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction 100 Mo( p , 2n ) 99m Tc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of 99 Mo/ 99m Tc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron. On this ground, an outline of the essential steps that should be implemented for setting up a hospital radiopharmacy aimed at the occasional production of Tc-99m by a small cyclotron is discussed. These include (1) target production, (2) irradiation conditions, (3) separation/purification procedures, (4) terminal sterilization, (5) quality control, and (6) Mo-100 recovery. To address these issues, a comprehensive technology for cyclotron-production of Tc-99m, developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL-INFN), will be used as a reference example. [ABSTRACT FROM AUTHOR]

Combination-based chemotherapies have been the standard treatment for multiple solid tumors since the 1960s. Combined therapies where both agents have toxicity results in dose-limiting effects. α- tocopherol succinate (TS) is an analogue of vitamin E that exhibits antitumor properties in the absence of toxicity. Hence, its combination with a frontline chemotherapy, doxorubicin (DOX) is an alternative to increase antitumor efficacy. Therefore, the aim of this work was to evaluate the antitumor activity of nanostructed lipid carriers (NLC) loaded with TS and DOX. The NLC-TS-DOX were prepared, characterized and radiolabeled with technetium-99m. Cytotoxicity studies were performed in vitro , using two breast cancer cell lines, MDA-MB-231 and 4T1. Biodistribution and antitumor activity were evaluated in 4T1 tumor-bearing mice. The results showed that NLC-TS-DOX had a small diameter (85 nm) and a long blood clearance (T 1/2 β = 1107.71 min) that consequently resulted in a higher tumor uptake compared to contralateral muscle for up to 48 h. Drug combination studies in MDA-MB-231 and 4T1 cells showed a combination index below 0.8 at ED 50-90 for both cell lines. Interestingly, a high synergism was found at ED 90. Antitumor activity showed a better control of tumor growth for animals treated with NLC-ST-DOX. The small particle size, along with the EPR effect and the controlled release of DOX from the particle, associated with the synergic combination between TS and DOX led to an increase of the antitumor efficacy. Therefore, NLC-TS-DOX can be considered a plausible alternative to improve antitumor efficacy in DOX therapeutic regimens. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study was to evaluate the ability of D (LPR), a novel retro-inverso peptidomimetic derivative for imaging colon cancer. Methods Two different D (LPR) analogs were designed and compared based on conjugation of HYNIC at peptide's C or N terminal and then labeled with technetium-99m using tricine/EDDA as an exchange coligands. The radiolabeled conjugates were assessed for in vitro stability in saline and serum. The VEGFR-1 and NRP-1 receptors affinity, in vitro internalization and also dissociation Constance was evaluated. SPCET imaging and biodistribution studies were performed in nude mice bearing HT-29 xenograft tumors. Results Both peptides labeled with technetium-99m in high radiochemical yield (˃97%). Peptide stability studies indicated a high metabolic stability of the radiopeptides in solution and serum. In vitro blocking studies demonstrated specific binding and internalization of [ 99m Tc]Tc-HYNIC-peptides in cultured HUVEC cells. The K d value for 99m Tc-peptide 1 and 99m Tc-peptide 2 were found to be 56.8 ± 12.9 nM and 71.6 ± 17.9 nM respectively. The tumor to muscle ratio was significant at 0.5 and 1 h after injection (4.5 and 4 for 99m Tc-peptide 1 and 4.9 and 4.4 for 99m Tc-peptide 2 at 0.5 and 1 h p.i. respectively). SPECT imaging studies revealed that both radioconjugates had prominent activity accumulation in VEGFR-1 and NRP-1 expressing HT-29 tumors. Conclusion This study is the first instance of using a radiolabeled retro-inverso peptide for tumor imaging which is a promising tool to improve the performance of fragile peptide probes in vivo as imaging agents and warrant further investigations in other peptide-target systems. [ABSTRACT FROM AUTHOR]

The radionuclides 99m Tc and 57 Co were standardized via absolute liquid scintillation counting techniques. We provide the first technical report on the absolute standardization of 99m Tc using 4 π (LS) e - γ coincidence counting. The low detection efficiency of low-energy conversion electrons translates into a large efficiency extrapolation range. A simulation indicated that the γ -ray interacting with the liquid scintillator introduces curvature to the count rate vs. efficiency relationship, the approximation of the functional form used for extrapolation providing the main measurement uncertainty for 99m Tc. A detection efficiency analysis for both radionuclides is presented. Results from the standardizations, and SIRTI and SIR comparison exercises are reported. [ABSTRACT FROM AUTHOR]

When tagged with a suitable radionuclide, the cancer targeting properties of trans -resveratrol could be utilized to locate cancerous sites in the body using radionuclide imaging technique. However, the polyphenol due to its rapid and extensive metabolism exhibits low bioavailability in vivo . The study was designed to enhance the cancer targeting efficacy of radiolabeled resveratrol using nano-based technology. Technetium-99m labeled resveratrol loaded gold nanoparticles (Res-AuNP) were synthesized, characterized and evaluated for their cancer targeting efficacy in HT29 colon cancer cells and in animal cancer model. Results of various investigations were compared to corresponding results obtained for 99m Tc-AuNP and 99m Tc-resveratrol. Cancer cell internalization observed for 99m Tc-Res-AuNP was significantly higher than that of 99m Tc-AuNP and 99m Tc-resveratrol. Also, a gradual rise in target to nontarget uptake with time was observed following i.v. administration of 99m Tc-Res-AuNP to colon tumor bearing rats, demonstrating better in vivo targeting of colon adenocarcinoma with 99m Tc-Res-AuNP when compared to 99m Tc-resveratrol. [ABSTRACT FROM AUTHOR]

Mesalamine (5-ASA) consists of the first-line therapy for the treatment of ulcerative colitis; however, it has low bioavailability, can cause several systemic adverse events, and has low treatment adherence due to the inconvenient dosing scheme. In this work, a new drug delivery system consisting of chondroitin sulfate linked to 5-ASA was synthesized using a carbodiimide as conjugating agent. The system was characterized by spectroscopic techniques (UV, ATR-FTIR, XRD, and NMR 1 H) and thermal analysis (TG/DTG and DSC), suggesting the conjugation between the drug and the polymer. The in vitro release and the corresponding kinetics were also evaluated, revealing that approximately 40% of the drug linked was released at pH 9 for up to 50 h, following Higuchi's model. The conjugate did not show cytotoxicity for the human monocytic cell line at the doses tested, and an in vivo biodistribution study showed that the conjugate remained in the lower GIT for up to 8 h with no uptake in the upper GIT. These data corroborate with the radiation found per segment of GIT and in blood. For this last test the conjugate was radiolabeled with Technetium-99m to allow the scintigraphy evaluation and radiation quantification. In conclusion, the polymeric conjugate was successfully synthesized and demonstrated a mucoadhesiveness on the colon as desired, thus supporting its potential use in the treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a specie of great medical importance associated with many infections as bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device related infections. Early identification of infectious foci is crucial for successful treatment. Scintigraphy could contribute to this purpose since specific radiotracers were available. Aptamers due to their high specificity have great potential for radiopharmaceuticals development. In the present study scintigraphic images of S. aureus infectious foci were obtained using specific S. aureus aptamers radiolabeled with 99m Tc. [ABSTRACT FROM AUTHOR]

The widely-used gamma-emitter Tc-99m has been shown to lead to optical emissions in mice and glass. We investigated the possibility that these emissions are due to the Cerenkov effect and whether the light emitted is proportional to local dose. By using a Geant4 Monte Carlo model matched to an experimental measurement, we show that the light detected by a small animal optical imaging system provides a 2D map of the dose throughout a glass sample. We conclude that radioluminescence from Tc-99m can be used to quantitatively measure dose in transparent materials, which could have applications in dosimetry and quality assurance. [ABSTRACT FROM AUTHOR]

Nuclear medicine clinicians are still waiting for the optimal scintigraphic imaging agents capable of distinguishing between infection and inflammation, and between fungal and bacterial infections. Aptamers have several properties that make them suitable for molecular imaging. In the present study, a peptidoglycan aptamer (Antibac1) was labeled with 99m Tc and evaluated by biodistribution studies and scintigraphic imaging in infection‐bearing mice. Labeling with 99m Tc was performed by the direct method and the complex stability was evaluated in saline, plasma and in the molar excess of cysteine. The biodistribution and scintigraphic imaging studies with the 99m Tc-Antibac1 were carried out in two different experimental infection models: Bacterial-infected mice ( S. aureus) and fungal-infected mice ( C. albicans ). A 99m Tc radiolabeled library, consisting of oligonucleotides with random sequences, was used as a control for both models. Radiolabeling yields were superior to 90% and 99m Tc‐Antibac1 was highly stable in presence of saline, plasma, and cysteine up to 6 h. Scintigraphic images of S. aureus infected mice at 1.5 and 3.0 h after 99m Tc‐Antibac1 injection showed target to non-target ratios of 4.7 ± 0.9 and 4.6 ± 0.1, respectively. These values were statistically higher than those achieved for the 99m Tc‐library at the same time frames (1.6 ± 0.4 and 1.7 ± 0.4, respectively). Noteworthy, 99m Tc‐Antibac1 and 99m Tc‐library showed similar low target to non-target ratios in the fungal-infected model: 2.0 ± 0.3 and 2.0 ± 0.6 for 99m Tc‐Antibac1 and 2.1 ± 0.3 and 1.9 ± 0.6 for 99m Tc‐library, at the same times. These findings suggest that the 99m Tc‐Antibac1 is a feasible imaging probe to identify a bacterial infection focus. In addition, this radiolabeled aptamer seems to be suitable in distinguishing between bacterial and fungal infection. [ABSTRACT FROM AUTHOR]

Introduction Radiolabeled GLP-1 and its analog Exendin-4, have been employed in diabetes and insulinoma. No protocol in conventional Diet-Induced Obesity (DIO), and Diet-Restricted Obesity (DRO), has been identified. Aiming to assess pancreatic beta cell uptake in DIO and DRO, a protocol was designed. Methods GLP-1-βAla-HYNIC and HYNIC-βAla-Exendin-4 were labeled with technetium-99m. Four Swiss mouse models were adopted: Controls (C), Alloxan Diabetes Controls (ADC), DIO and DRO. Biodistribution and ex-vivo planar imaging were documented. Results Radiolabeling yield was in the range of 97% and both agents were hydrophilic. Fasting Blood Glucose (FBG) was 79.2 ± 8.2 mg/dl in C, 590.4 ± 23.3 mg/dl in ADC, 234.3 ± 66.7 mg/dl in DIO, and 96.6 ± 9.3 in DRO (p = 0.010). Biodistribution confirmed predominantly urinary excretion. DIO mice exhibited depressed uptake in liver and pancreas, for both radiomarkers, in the range of ADC. DRO only partially restored such values. 99m Tc-HYNIC-βAla-Exendin-4 demonstrated better results than GLP-1-βAla-HYNIC- 99m Tc. Conclusions 1) Diet-induced obesity remarkably depressed beta cell uptake; 2) Restriction of obesity failed to normalize uptake, despite robust improvement of FBG; 3) HYNIC-βAla-Exendin-4 was the most useful marker; 4) Further studies are recommended in obesity and dieting, including bariatric surgery. [ABSTRACT FROM AUTHOR]

Elevated density of gastrin releasing peptide receptors (GRPR) in prostate cancer has led to exploration of several radiolabeled peptides for imaging and staging of the disease. The GRPR antagonist peptide RM2 has been successfully conjugated with several chelators and radiolabeled with gallium-68. The goal of this study was to synthesize a 99mTc-labeled probe and investigate its potential for SPECT imaging of prostate cancer. Towards this HYNIC-RM2 peptide conjugate was synthesized, radiolabeled with 99mTc and evaluated in GRPR-positive PC3 tumor xenografts. HYNIC-RM2 was manually synthesized by standard Fmoc solid phase strategy and radiolabeled with 99mTc. In vitro cell studies were performed in GRPR-positive human prostate carcinoma (PC3) cells. Metabolic stability studies of [99mTc]Tc-HYNIC-RM2 were performed in normal mice in the presence as well as absence of neutral endopeptidase (NEP) inhibitor, phosphoramidon (PA). Biodistribution and imaging studies of [99mTc]Tc-HYNIC-RM2 were performed in SCID mice bearing PC3-xenograft. [99mTc]Tc-HYNIC-RM2 exhibited high binding affinity in low nanomolar range (K d = 1.83 ± 0.31 nM). Metabolic stability studies in mice indicated that in the absence of PA, radiolabeled peptide was about 65 % intact in the blood at 15 min p.i., whereas proportion of intact radiolabeled peptide was enhanced to 90 % on co-administration of PA. Biodistribution studies in PC3 tumor bearing mice demonstrated high tumor uptake (8.02 ± 0.9%ID/g and 6.13 ± 0.44%ID/g at 1 h and 3 h p.i.). Co-administration of PA with the radiolabeled peptide resulted in further enhancement of tumor uptake (14.24 ± 0.76 % ID/g and 11.71 ± 0.59%ID/g at 1 h and 3 h p.i.). SPECT/CT images of [99mTc]Tc-HYNIC-RM2 could clearly visualize the tumor. Significant (p < 0.001) reduction in the tumor uptake with a co-injected blocking dose of unlabeled peptide ascertained the GRPR specificity of [99mTc]Tc-HYNIC-RM2. Encouraging results obtained in biodistribution and imaging studies indicate the potential of [99mTc]Tc-HYNIC-RM2 for further exploration as GRPR targeting agent. 99mTc-based SPECT analogue of [68Ga]Ga-RM2 for targeting GRPR was prepared by conjugating HYNIC chelator at the N-terminus of RM2 peptide (DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2) instead of DOTA chelator. Promising preclinical results exhibited by [99mTc]Tc-HYNIC-RM2 warrant its potential for clinical translation. [Display omitted] • Synthesis of GRPR targeting HYNIC-RM2 peptide for preparing SPECT probe • Technetium-99m labeling of HYNIC-RM2 using wet protocol as well as freeze-dried kit • High affinity and specificity of [99mTc]Tc-HYNIC-RM2 towards GRPR • In-vivo stability enhanced by co-administration of enzyme inhibitor phosphoramidon • High tumor uptake of [99mTc]Tc-HYNIC-RM2 well visualized in the SPECT/CT images [ABSTRACT FROM AUTHOR]

Al 2 O 3 nanoparticle is effectively used as an adsorbent for the low specific activity of molybdenum-99 (99Mo). The Al 2 O 3 nanoparticle was synthesized by the green synthesis method using Hibiscus rosa-sinensis leaf extract (HRE). The Al 2 O 3 nanoparticle synthesized using 10% of the HRE has a crystallite size of 4.9 nm, a surface area of 254.6 m2/g, a pore size of 9.1 nm, a pore volume of 0.58 cm3/g and has a Mo adsorption capacity of 43.4 ± 6.1 mg Mo/g. • Al 2 O 3 nanoparticle was prepared by using Hibiscus rosa-sinensis leaf extract (HRE). • The alkaloid content in the HRE as a base source for the hydrolysis reaction. • The other secondary metabolites in the HRE have a role as capping agents, stabilizers, or templates. • The synthesized Al 2 O 3 nanoparticle was used as a molybdenum-99 (99Mo) adsorbent. [ABSTRACT FROM AUTHOR]

99m Tc–tricarbonyl–vardenafil was specifically radiosynthesized for diagnostic evaluation of erectile dysfunction with a radiochemical yield ~97.2%. It was stable in saline up to 15 h and in serum for more than 6 h. The radiocomplex was lipophilic with a partition coefficient ~1.32 and plasma protein binding 72–76%. Its structure was determined using molecular mechanics and confirmed by NMR. In-silico docking to its target PDE 5 enzyme was performed. The radiocomplex inhibitory activity was assessed and its IC 50 was 0.7 nM. Biodistribution in normal rats and biological evaluation in rat models of erectile dysfunction were performed. The results strongly suggested that 99m Tc–tricarbonyl–vardenafil is a good candidate to image erectile dysfunction in humans. [ABSTRACT FROM AUTHOR]

The design and fabrication of a fully-automated, remotely controlled module for the extraction and purification of technetium-99m (Tc-99m), produced by proton bombardment of enriched Mo-100 molybdenum metallic targets in a low-energy medical cyclotron, is here described. After dissolution of the irradiated solid target in hydrogen peroxide, Tc-99m was obtained under the chemical form of 99m TcO 4 - , in high radionuclidic and radiochemical purity, by solvent extraction with methyl ethyl ketone (MEK). The extraction process was accomplished inside a glass column-shaped vial especially designed to allow for an easy automation of the whole procedure. Recovery yields were always >90% of the loaded activity. The final pertechnetate saline solution Na 99m TcO 4 , purified using the automated module here described, is within the Pharmacopoeia quality control parameters and is therefore a valid alternative to generator-produced 99m Tc. The resulting automated module is cost-effective and easily replicable for in-house production of high-purity Tc-99m by cyclotrons [ABSTRACT FROM AUTHOR]

Technetium-99m, the decay product of molybdenum-99, is the most used medical isotope in diagnostic imaging. The future disruptions of molybdenum-99 supply, due to the final shut down of some old producing reactors, has led some current global supplies to plan the expansion of their production capacity. While other countries are developing own production facilities to supply their domestic demand. The global increase of molybdenum-99 production in the coming years could increase by about five times the current demand, with about the 50 percent of additional production in North America. Xenon radionuclides are an inevitable by-product of the nuclear plants production, and their periodically release into the atmosphere, contribute to the background that is also revealed by the IMS stations of the CBTO treaty. In this framework, the development of new technologies, posing no risk in relation to nuclear proliferation and do not result in emissions of radioxenon, could mitigate the issues related to the forecast increase of molybdenum-99 production worldwide. In Italy, an alternative 99Mo production project, the project ENEA Sorgentina, based on the irradiation of molybdenum by neutrons produced by a deuterium-tritium nuclear fusion process, is under development. This facility will not release radioxenon into the atmosphere, so it will not affect the background value in the atmosphere in Southern Europe. • Overview of all current and planned 99Mo production capabilities. • The atmospheric background due to the anthropogenic radioxenon emissions is a challenge for nuclear explosion monitoring. • Savings of radioxenon emissions using fusion-based nuclear reactions. [ABSTRACT FROM AUTHOR]

[Display omitted] Epidermal growth factor receptors (EGFR) of tyrosine kinase (TK) have shown high expression levels in most cancers and are considered a promising target for cancer diagnosis and therapy. Expanding the investigation for novel targeted radiopharmaceuticals, an EGFR inhibitor such as 4-aminoquinazoline derivatives along with a radionuclide such as technetium-99m (99mTc) could be ideal. Thus, we report herein the synthesis, characterization, and biological evaluation of new "4 + 1" mixed-ligand ReIII- and 99mTcIII-complexes of the general formula [99mTc][Tc(NS 3)(CN-R)] bearing tris(2-mercaptoethyl)-amine (NS 3) as the tetradentate tripodal ligand and a series of isocyanide derivatives (CN-R) of tyrosine kinase inhibitor (3-bromophenyl)quinazoline-4,6-diamine as the monodentate ligand. The quinazoline isocyanide derivatives 4a - d were prepared in two steps and reacted with the [Re(NS 3)PMe 2 Ph] precursor leading to the final complexes 5a - d in high yield. All compounds were characterized by elemental analysis, IR, and NMR spectroscopies. In vitro studies, for their potency to inhibit the cell growth, using intact A431 cells indicate that the quinazoline derivatives 4a-d and the Re complexes 5a-d significantly inhibit the A431 cell growth. In addition, the EGFR autophosphorylation study of complex 5b shows an IC 50 value in the nanomolar range. The corresponding "4 + 1" 99mTc-complexes 6a - d were prepared by employing the [99mTc]TcEDTA intermediate and the appropriate monodentate 4a - d in a two-step synthetic procedure with a radiochemical yield (RCY) from 63 to 77 % and a radiochemical purity (RCP) > 99 % after HPLC purification. Their structures have been established by HPLC comparative studies using the well-characterized Re-complexes 5a - d as reference. All 99mTc-complexes remain stable for at least 6 h, and their logD 7.4 values confirmed their anticipated lipophilic character. Biodistribution studies in healthy Swiss albino mice of 99mTc-complexes showed hepatobiliary excretion and initial fast blood clearance. Complex 6b was also tested in Albino SCID mice bearing A431 tumors and showed rapid tumor uptake at 5 min (2.80 % ID/g) with a moderate tumor/muscle ratio (2.06) at 4 h p.i. The results encourage further investigation for this type of 99mTc-complexes as single-photon emission computed tomography (SPECT) radio agents for imaging tumors overexpressing EGFR. [ABSTRACT FROM AUTHOR]

Two bisphosphonate isocyanide derivatives (CNALN and CNPAM) could be easily synthesized and the corresponding [99mTc][Tc(I)]+ labeled complexes were successfully prepared. The biodistribution and single photon emission computed tomography (SPECT) imaging studies in mice revealed [99mTc]Tc-CNALN had an obvious accumulation in bone, suggesting it would be a promising bone-seeking agent. [Display omitted] In order to develop 99mTc-labeled complexes with bisphosphonate isocyanide as novel bone imaging agents, two bisphosphonate isocyanide derivatives (CNALN and CNPAM) were synthesized and radiolabeling was performed for preparing the corresponding [99mTc]Tc(I) complexes. [99mTc]Tc-CNALN and [99mTc]Tc-CNPAM were obtained with high radiochemical purity and showed good in vitro stability. Both of them were hydrophilic and had high affinity to hydroxyapatite. The biodistribution studies in mice revealed [99mTc]Tc-CNALN showed higher bone/background ratios at 60 min post-injection. In single photon emission computed tomography (SPECT) imaging study, [99mTc]Tc-CNALN had an obvious accumulation in bone, suggesting it would be a promising bone-seeking agent. [ABSTRACT FROM AUTHOR]

Introduction Technetium-99m ( 99m Tc) is a radionuclide commonly used in nuclear medicine to obtain 99m Tc-radiopharmaceuticals, which can be used to evaluate either physiological processes or changes related to diseases. It is also used in some experimental studies. Streptozotocin (STZ) administration to rodents causes lesions in very early stages and induces severe and permanent diabetes. Most morbidity of schistosomiasis mansoni is attributed to a granulomatous inflammatory response and associated liver fibrosis. This study was designed to investigate whether STZ administration and schistosomiasis modify the biodistribution of the radiopharmaceutical sodium 99m Tc-pertechnetate. Methods Adult female mice were infected by exposure to 100 Schistosoma mansoni cercariae (BH strain, Belo Horizonte, Brazil) and euthanized after nine weeks. STZ was administered by a single intraperitoneal injection of 100 mg/kg body weight, 3 or 15 days before euthanasia. Each animal received 100 μl of sodium (Na) 99m Tc-pertechnetate ( 99m TcO 4 − ) (740 kBq). The animals were divided into four groups: A, uninfected; B, infected; C, uninfected + STZ; and D, infected + STZ. Blood, brain, thyroid, heart, lungs, liver, spleen, pancreas and kidneys were removed. The radioactivity was counted and the percentage of the injected dose of Na 99m TcO 4 per gram of the organ (% ID/g) was determined. Results Three days after the STZ injection, there was a decrease of Na 99m TcO 4 uptake by the liver, lungs, pancreas and kidneys ( p < 0.05) in group D when compared with group A. After 15 days, the decrease of Na 99m TcO 4 uptake occurred also in the brain, thyroid, heart, spleen and blood ( p < 0.05) in group D. Conclusion We demonstrated modifications on the biodistribution of Na 99m TcO 4 due to STZ administration and schistosomiasis, possibly due to physiological alterations in some organs. Advances in Knowledge and Implications for Patient Care The biodistribution of radiopharmaceutical Na 99m TcO 4 should be carefully evaluated in subjects with diabetes and/or schistosomiasis infection. [ABSTRACT FROM AUTHOR]

New rhenium(I) tricarbonyl complexes with the quinolone antimicrobial agents oxolinic acid (Hoxo) and enrofloxacin (Herx) and containing methanol, triphenylphosphine (PPh 3 ) or imidazole (im) as unidentate co-ligands, were synthesized and characterized. The crystal structure of complex [Re(CO) 3 (oxo)(PPh 3 )]∙0.5MeOH was determined by X–ray crystallography. The deprotonated quinolone ligands are bound bidentately to rhenium(I) ion through the pyridone oxygen and a carboxylate oxygen. The binding of the rhenium complexes to calf-thymus DNA (CT DNA) was monitored by UV spectroscopy, viscosity measurements and competitive studies with ethidium bromide; intercalation was suggested as the most possible mode and the DNA-binding constants of the complexes were calculated. The rhenium complex [Re(CO) 3 (erx)(im)] was assayed for its topoisomerase IIα inhibition activity and was found to be active at 100 μM concentration. The interaction of the rhenium complexes with human or bovine serum albumin was investigated by fluorescence emission spectroscopy (through the tryptophan quenching) and the corresponding binding constants were determined. The tracer complex [ 99m Tc(CO) 3 (erx)(im)] was synthesized and identified by comparative HPLC analysis with the rhenium analog. The 99m Tc complex was found to be stable in solution. Upon injection in healthy mice, fast tissue clearance of the 99m Tc complex was observed, while both renal and hepatobiliary excretion took place. Preliminary studies in human K-562 erythroleukemia cells showed cellular uptake of the 99m Tc tracer with distribution primarily in the cytoplasm and the mitochondria and less in the nucleus. These preliminary results indicate that the quinolone 99m Tc/Re complexes show promise to be further evaluated as imaging or therapeutic agents. [ABSTRACT FROM AUTHOR]

Along with anti-cancer drug delivery researches, many efforts have been done to develop new tracers for diagnostic applications. Based on advances in molecular imaging, nanoparticles can be used to visualize, characterize and measure biological process at molecular and cellular level. Therefore, the purpose of this study was to synthesize, characterize and radiolabeled mesoporous silica nanoparticles (MSNs) for in vivo applications. The nanoparticles were synthesized, functionalized with 3-aminopropyltriethoxysilane (APTES) and then, anchored with diethylenetriaminepentaacetic acid (DTPA). Particles were physicochemical characterized by elemental analysis (CHN), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and zeta potential, and were morphologically characterized by scanning electron microscopy (SEM), low-angle X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. Results indicate that functionalization process was successfully achieved. Next, functionalized silica nanoparticles were radiolabeled with technetium-99m showing high radiochemical yields and high radiolabeled stability. These findings allow the use of the particles for in vivo applications. Biodistribution and scintigraphic images were carried out in healthy mice in order to determine the fate of the particles. Results from in vivo experiments showed high uptake by liver, as expected due to phagocytosis. However, particles also showed a significant uptake in the lungs, indicated by high lung-to-non-target tissue ratio. In summary, taking into account the great potential of these silica mesoporous structures to carry molecules this platform could be a good strategy for theranostic purposes. [ABSTRACT FROM AUTHOR]

Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with 99m Tc) with high in silico affinity. The novel prepared 99m Tc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors . 99m Tc-amitrole was radio-synthesized with a high radiochemical yield (89.7 ± 3.25). It showed in vitro stability for up to 6 h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60 min post-injection. The data described previously could recommend 99m Tc-amitrole as potential targeting scintigraphic probe for solid tumor imaging. [ABSTRACT FROM AUTHOR]

Nanoscale celluloses have recently gained an increasing interest in modern medicine. In this study, we investigated the properties of plant derived nanofibrillar cellulose (NFC) as an injectable drug releasing hydrogel in vivo . We demonstrated a reliable and efficient method of technetium-99m-NFC labeling, which enables us to trace the in vivo localization of the hydrogel. The release and distribution of study compounds from the NFC hydrogel after subcutaneous injection in the pelvic region of BALB/c mice were examined with a multimodality imaging device SPECT/CT. The drug release profiles were simulated by 1-compartmental models of Phoenix® WinNonlin®. The NFC hydrogel remained intact at the injection site during the study. The study compounds are more concentrated at the injection site when administered with the NFC hydrogel compared with saline solutions. In addition, the NFC hydrogel reduced the elimination rate of a large compound, technetium-99m-labeled human serum albumin by 2 folds, but did not alter the release rate of a small compound 123 I-β-CIT (a cocaine analogue). In conclusion, the NFC hydrogels is easily prepared and readily injected, and it has potential use as a matrix for controlled release or local delivery of large compounds. The interactions between NFC and specific therapeutic compounds are possible and should be investigated further. [ABSTRACT FROM AUTHOR]

Introduction New 188 Re and 99m Tc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N] 2+ (M= 99m Tc, 188 Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands. Methods The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N] 2+ core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas the monodentate ligand was a tertiary phosphine. The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re≡N] 2+ core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small-animal YAP(S)PET tomograph. Conclusion New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high-yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re-188 radiopharmaceuticals exhibit identical biological properties. [ABSTRACT FROM AUTHOR]

Abstract: Bone-seeking radiopharmaceuticals such as radiolabeled bisphosphonates (BPs) bind to bone matrix in areas of increased bone turnover, characteristic of metastization sites, delivering selectively γ radiation or β− particles for bone imaging or bone-pain palliation, respectively. Recent preclinical studies suggest that nitrogen-containing BPs may have also a direct anti-tumor activity. We have recently introduced a set of 99mTc-organometallic complexes that allow the simultaneous delivery of γ radiation and BPs to bone tissue. Aimed at finding complexes of the same family with improved bone-seeking properties and adequate tumor cell uptake profile, we have synthesized novel complexes of the type fac-[M(CO)3(k 3-L)]+ (M = 99mTc/Re, Tc3/Re3–Tc5/Re5) stabilized by bifunctional chelators with different molecular weight, overall charge, (lipo)hydrophilic nature and different positions of BP attachment. Biodistribution studies in normal mice have shown that Tc3, where the BP unit (alendronate) is at position 4 of the pyrazolyl ring, presents the most favorable pharmacokinetic profile with fast blood clearance, high bone uptake (17.1 ± 3.6% I.A./g at 1 h p.i.), and higher bone-to-blood and bone-to-muscle ratios than the gold standard 99m Tc-MDP. Cellular uptake studies in the MDAMB231 metastatic breast cancer cells showed a maximal uptake of 4–6% at 6 h incubation for all complexes. Interestingly, cell fragmentation studies have shown that Tc3 presents the highest accumulation in the cytosol (35%). The promising biological profile of the BP-containing complex Tc3 encourages further research towards evaluation of 188Re congeners for potential therapeutic applications. [Copyright &y& Elsevier]

Abstract: Tris(pyrazolyl)methane chelators, L1–L3, containing one or two ether groups at different positions of the azole rings, were synthesized and fully characterized. These chelators enabled the synthesis of fac-[99mTc(CO)3{HC[4-(ROCH2)pz]3}]+ (R = Me (Tc1), Et (Tc2)) and fac-[99mTc(CO)3{HC[3,5-(EtOCH2)2pz]3}]+ (Tc3) which were identified by HPLC in comparison with the rhenium counterparts. The evaluation of Tc1–Tc3 in CD-1 mice has shown that the number and/or nature of the ether groups greatly influence the biodistribution profile, pharmacokinetics and metabolic stability of these complexes. Tc1 and Tc2, bearing a unique ether substituent at the 4-position of the pyrazolyl ring, undergo metabolic transformation in vivo while Tc3 is not metabolized. The metabolization of Tc1 and Tc2 enhanced their rate of excretion but, most probably, also justify their negligible heart uptake in contrast with the high heart uptake of congener non-metabolizable complexes (99mTc-DMEOP and 99mTc-TMEOP), which have recently emerged as potential myocardial imaging agents. The attempts made to identify the metabolites of Tc1 and Tc2 have shown that the metabolization of these compounds must involve the ether functions with probable formation of carboxylic acid derivatives. A comparative study with the congener fac-[99mTc(CO)3{[4-(MeOCH2)pz](CH2)2NH(CH2)2NH2}]+ (Tc6) led us to confirm the formation of such type of metabolites. In fact, Tc6 is also metabolized in mice with formation of fac-[99mTc(CO)3{[4-(HOCH2)pz](CH2)2NH(CH2)2NH2}]+ (Tc7) and fac-[99mTc(CO)3{[4-(HOOC)pz](CH2)2NH(CH2)2NH2}]+ (Tc8), which were chemically identified by HPLC in comparison with the Re congeners (Re7 and Re8). [Copyright &y& Elsevier]

Abstract: Due to the unforeseen maintenance issues at the National Research Universal (NRU) reactor at Chalk River and coincidental shutdowns of other international reactors, a global shortage of medical isotopes (in particular technetium-99m, Tc-99m) occurred in 2009. The operation of these research reactors is expensive, their age creates concerns about their continued maintenance and the process results in a large amount of long-lived nuclear waste, whose storage cost has been subsidized by governments. While the NRU has since revived its operations, it is scheduled to cease isotope production in 2016. The Canadian government created the Non-reactor based medical Isotope Supply Program (NISP) to promote research into alternative methods for producing medical isotopes. The NRC was a member of a collaboration looking into the use of electron linear accelerators (LINAC) to produce molybdenum-99 (Mo-99), the parent isotope of Tc-99m. This paper outlines NRC’s involvement in every step of this process, from the production, chemical processing, recycling and preliminary animal studies to demonstrate the equivalence of LINAC Tc-99m with the existing supply. This process stems from reusing an old idea, reduces the nuclear waste to virtually zero and recycles material to create a green solution to Canada's medical isotope shortage. [Copyright &y& Elsevier]

Highlights: [•] p-Tertbutylcalix[4]arene nanoemulsion complexed with 99mTc, 131I &201Tl. [•] p-Tertbutylcalix[4]arene formulation shows wide spectrum decontamination. [•] The nanoemulsion is reasonably stable and skin-safe for application. [Copyright &y& Elsevier]