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The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99m Tc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99m Tc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using D Pro-Gly as the linker was synthesized and three 99m Tc-labeled complexes ([ 99m Tc]Tc-EUKPG-EDDA, [ 99m Tc]Tc-EUKPG-TPPTS, [ 99m Tc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [ 99m Tc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro . Therefore, [ 99m Tc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.

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 ( 99m Tc) 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 99m Tc. A group of mice were injected intravenously (in tail vein) with 4-6 MBq of [ 99m Tc]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 99m Tc 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 [ 99m Tc]Tc-CMS 99m Tc and we could study its biodistribution in healthy mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fibroblast activation protein (FAP) is expressed in the microenvironment of most human epithelial tumors. 68 Ga-labeled FAP inhibitors based on the cyanopyrrolidine structure (FAPI) are currently used for the detection of the tumor microenvironment by PET imaging. This research aimed to design, synthesize and preclinically evaluate a new FAP inhibitor radiopharmaceutical based on the 99m Tc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid ( 99m Tc-iFAP) structure for SPECT imaging. Molecular docking for affinity calculations was performed using the AutoDock software. The chemical synthesis was based on a series of coupling reactions of 6-hidrazinylnicotinic acid (HYNIC) and D-alanine to a boronic acid derivative. The iFAP was prepared as a lyophilized formulation based on EDDA/SnCl 2 for labeling with 99m Tc. The radiochemical purity (R.P.) was verified via ITLC-SG and reversed-phase radio-HPLC. The stability in human serum was evaluated by size-exclusion HPLC. In vitro cell uptake was assessed using N30 stromal endometrial cells (FAP positive) and human fibroblasts (FAP negative). Biodistribution and tumor uptake were determined in Hep-G2 tumor-bearing nude mice, from which images were acquired using a micro-SPECT/CT. The iFAP ligand ( Ki = 0.536 nm, AutoDock affinity), characterized by UV-Vis, FT-IR, 1 H-NMR and UPLC-mass spectroscopies, was synthesized with a chemical purity of 92%. The 99m Tc-iFAP was obtained with a R.P. >98%. In vitro and in vivo studies indicated high radiotracer stability in human serum (>95% at 24 h), specific recognition for FAP, high tumor uptake (7.05 ± 1.13% ID/g at 30 min) and fast kidney elimination. The results found in this research justify additional dosimetric and clinical studies to establish the sensitivity and specificity of the 99m Tc-iFAP.

Auger electron-emitters increasingly attract attention as potential radionuclides for molecular radionuclide therapy in oncology. The radionuclide technetium-99m is widely used for imaging; however, its potential as a therapeutic radionuclide has not yet been fully assessed. We used MDA-MB-231 breast cancer cells engineered to express the human sodium iodide symporter-green fluorescent protein fusion reporter (hNIS-GFP; MDA-MB-231.hNIS-GFP) as a model for controlled cellular radionuclide uptake. Uptake, efflux, and subcellular location of the NIS radiotracer [ 99m Tc]TcO 4 - were characterised to calculate the nuclear-absorbed dose using Medical Internal Radiation Dose formalism. Radiotoxicity was determined using clonogenic and γ-H2AX assays. The daughter radionuclide technetium-99 or external beam irradiation therapy (EBRT) served as controls. [ 99m Tc]TcO 4 - in vivo biodistribution in MDA-MB-231.hNIS-GFP tumour-bearing mice was determined by imaging and complemented by ex vivo tissue radioactivity analysis. [ 99m Tc]TcO 4 - resulted in substantial DNA damage and reduction in the survival fraction (SF) following 24 h incubation in hNIS-expressing cells only. We found that 24,430 decays/cell (30 mBq/cell) were required to achieve SF 0.37 (95%-confidence interval = [SF 0.31 ; SF 0.43 ]). Different approaches for determining the subcellular localisation of [ 99m Tc]TcO 4 - led to SF 0.37 nuclear-absorbed doses ranging from 0.33 to 11.7 Gy. In comparison, EBRT of MDA-MB-231.hNIS-GFP cells resulted in an SF 0.37 of 2.59 Gy. In vivo retention of [ 99m Tc]TcO 4 - after 24 h remained high at 28.0% ± 4.5% of the administered activity/gram tissue in MDA-MB-231.hNIS-GFP tumours. [ 99m Tc]TcO 4 - caused DNA damage and reduced clonogenicity in this model, but only when the radioisotope was taken up into the cells. This data guides the safe use of technetium-99m during imaging and potential future therapeutic applications.

Absorption kinetics of solutes given with the subcutaneous administration of fluids is ill-defined. The gamma emitter, technitium pertechnetate, enabled estimates of absorption rate to be estimated independently using two approaches. In the first approach, the counts remaining at the site were estimated by imaging above the subcutaneous administration site, whereas in the second approach, the plasma technetium concentration-time profiles were monitored up to 8 hr after technetium administration. Boluses of technetium pertechnetate were given both intravenously and subcutaneously on separate occasions with a multiple dosing regimen using three doses on each occasion. The disposition of technetium after iv administration was best described by biexponential kinetics with a Vss of 0.30±0.11 L/kg and a clearance of 30.0±13.1 ml/min. The subcutaneous absorption kinetics was best described as a single exponential process with a half-life of 18.l6±3.97min by image analysis and a half-life of 11.58±2.48 min using plasma technetium time data. The bioavailability of technetium by the subcutaneous route was estimated to be 0.96±0.12. The absorption half-life showed no consistent change with the duration of the subcutaneous infusion. The amount remaining at the absorption site with time was similar when analyzed using image analysis, and plasma concentrations assuming multiexponential disposition kinetics and a first-order absorption process. Profiles of fraction remaining at the absorption site generated by deconvolution analysis, image analysis, and assumption of a constant first-order absorption process were similar. Slowing of absorption from the subcutaneous administration site is apparent after the last bolus dose in three of the subjects and can be associated with the stopping of the infusion. In a fourth subject, the retention of technetium at the subcutaneous site is more consistent with accumulation of technetium near the absorption site as a result of systemic recirculation. [ABSTRACT FROM AUTHOR]

Radiotracers labelled with technetium-99m ( 99m Tc) enable accessible diagnostic imaging of disease, provided that radiotracer preparation is simple. Whilst 99m Tc radiopharmaceuticals for imaging perfusion are routinely prepared from kits, and regularly used in healthcare, there are no 99m Tc-labelled receptor-targeted radiopharmaceuticals in widespread clinical use. This is in part due to the multistep radiosyntheses required for the latter. We demonstrate that the diphosphine, 2,3-bis(diphenylphosphino)maleic anhydride (BMA), is an excellent platform for preparation of kit-based, receptor-targeted 99m Tc-labelled radiotracers: its conjugates are simple to prepare and can be easily labelled with 99m Tc using one-step, kit-based protocols. Here, reaction of BMA with the α v β 3 -integrin receptor targeted cyclic peptide, Arg-Gly-Asp-DPhe-Lys (RGD), provided the first diphosphine-peptide conjugate, DP-RGD. DP-RGD was incorporated into a "kit", and addition of a saline solution containing 99m TcO 4 - to this kit, followed by heating, furnished the radiotracer [ 99m TcO 2 (DP-RGD) 2 ] + in consistently high radiochemical yields (>90%). The analogous [ReO 2 (DP-RGD) 2 ] + compound was prepared and characterised, revealing that both [ 99m TcO 2 (DP-RGD) 2 ] + and [ReO 2 (DP-RGD) 2 ] + consist of a mixture of cis and trans geometric isomers. Finally, [ 99m TcO 2 (DP-RGD) 2 ] + exhibited high metabolic stability, and selectively targeted α v β 3 -integrin receptors, enabling in vivo SPECT imaging of α v β 3 -integrin receptor expression in mice.

A series of "2 + 1" mixed ligand tricarbonyl complexes of the general formula fac-[Re/ 99m Tc/ 186 Re(CO) 3 (DDTC)(L)] containing diethyldithiocarbamate (DDTC) as a monoanionic bidentate ligand and a series of monodentate ligands L was synthesized, characterized and evaluated. The impact of ligand L on the radiochemical yield (RCY) and biodistribution of the final compounds was also investigated. DDTC and the appropriate L ligand [cyclohexyl isocyanide (cisc), tert-butyl isocyanide (tbi), triphenylphosphine (PPh 3 ), methyldiphenylphosphine (PPh 2 Me), triphenylarsine (AsPh 3 ), imidazole (im), and 4-aminopyridine (4AP)] readily reacted in equimolar amounts with the [Et 4 N] 2 [Re(CO) 3 Br 3 ] precursor to afford fac-[Re(CO) 3 (DDTC)(cisc)], Re1, fac-[Re(CO) 3 (DDTC)(tbi)], Re2, fac-[Re(CO) 3 (DDTC)(PPh 3 )], Re3, fac-[Re(CO) 3 (DDTC)(PPh 2 Me)], Re4, fac-[Re(CO) 3 (DDTC)(AsPh 3 )], Re5, fac-[Re(CO) 3 (DDTC)(im)], Re6 and fac-[Re(CO) 3 (DDTC)(4AP)], Re7, complexes in high yields (>80%). All Re complexes were fully characterized by IR, NMR, and in addition Re4, Re5, and Re7 with X-ray crystallography. Analogous reactions as performed with Re were subsequently explored on the 99m Tc and 186 Re-tracer levels using the corresponding fac-[ 99m Tc/ 186 Re(CO) 3 (H 2 O) 3 ] + precursor. Complexes 99m Tc1 - 99m Tc5, 186 Re1 and 186 Re3 were obtained in high radiochemical yield (>91%), while the complexes 99m Tc6, 99m Tc7 and 186 Re7 formed with radiochemical yields of 55%, 28%, and 75%, respectively. The 99m Tc and 186 Re-complexes were characterized by comparative HPLC analysis using the analogous Re complexes. During histidine and cysteine challenge experiments at 37 °C through 6 h, complexes 99m Tc1 - 99m Tc5 remained > 92% stable, while complexes 99m Tc6 and 99m Tc7 remained only 8% stable through 3 h. Similar studies for 186 Re-complexes showed that 186 Re1 and 186 Re3 remained > 95% stable for up to 48 h, while 186 Re7 had decreased to 7% after 3 h. LogD 7.4 data of 99m Tc1 - 99m Tc5, 186 Re1, and 186 Re3 complexes, which ranged from 2.59 to 3.39, suggested high lipophilicity. Biodistribution studies in healthy Swiss albino mice showed hepatobiliary excretion for 99m Tc1, 99m Tc2, and 99m Tc4, fast blood clearance for 99m Tc4, while high liver uptake and retention for 99m Tc3 and 99m Tc5 were measured. Moreover, 99m Tc2 showed high accumulation in the lungs with sustained retention (52.80% ID/g at 4 h p.i.) and significant brain uptake at 2 min p.i. (1.89% ID/g). The study showed the great influence of monodentate ligand in the synthesis and biodistribution of the mixed ligand complexes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The usage of radioactive Technetium 99m (Tc 99m ) colloid for the purpose of sentinel lymph node biopsy (SLNB) in early breast cancer is considered the gold standard in Germany. However, new tracers, such as near-infrared (NIR) imaging agents like indocyanine green (ICG) could offer an alternative in future, as they overcome drawbacks associated with radioactive Technetium 99m (Tc 99m ) like limited availability, high costs and radioactivity exposure for both patients and surgeons., Methods: In this double-arm retrospective study, we sought to establish the usefulness of indocyanine green as an alternative or an addition to the conventional Technetium 99m (Tc 99m ) in the identification of the SLN in early breast cancer., Results: Among the 161 patients who underwent primary SLNB, 34 patients had at least 1 SLN with metastasis. Among these patients with SLN metastasis, 33 had the SLN detected by ICG; while 31 had the SLN detected by Tc 99m . The conventional Technetium 99m radiotracer failed to detect 2 patients with metastasis in this Arm of the study. Among the 87 patients who underwent SLNB after NACT, 13 patients had at least 1 SLN with metastasis. Among these 13 patients with SLN metastasis, ICG and Tc 99m had detected the SLN among 12 patients, while 1 patient had been detected by ICG alone., Conclusions: Our results show that ICG is as effective as the radioisotope for SLNB even among patients who have undergone NACT. This trial is registered with the German Clinical Trial Register, ID: DRKS00013606.

The transmetalation reaction between zinc dithiocarbamates functionalized with organic groups and the cation fac-[ 99m Tc(H 2 O) 3 (CO) 3 ] + has been studied as a new strategy to bind biomolecules to this radionuclide for preparing radiopharmaceuticals with high molar activity. All complexes were obtained in high yields by heating at moderate temperatures and without subsequent purification. The chemical identity was ascertained by HPLC comparison with the homologous rhenium complexes. Stability studies in cysteine solution and serum have shown a good stability of the coordination set fac-[ 99m Tc(CO) 3 (SS)(P)]. Preliminary biological studies of the radiocomplex functionalized with D-(+)-glucosamine with carcinoma cells have been performed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nanomedicine is a highly demanded discipline. Liposomes have seen an increased attention due to their physicochemical properties that allow them to act as nanocarriers of drugs and also of radioisotopes that can be used to diagnose and treat cancer. In order to obtain a novel permeability cancer imaging agent based on 99m Tc-labeled liposomes, we describe microwave-assisted synthesis of stearyl 6-(benzylidenehydrazinyl) nicotinamide lipid, which was included in two formulations: nanometric hydrazinonicotinic acid (HYNIC) liposome and its PEGylated coated analogue, HYNIC-PEG liposome. Radiolabeling with 99m Tc via stearyl 6-(benzylidenehydrazinyl) nicotinamide was found to be easy, reproducible, and stable, revealing high radiochemical purity (94 ± 1.7%) for both liposomal formulations. Biodistribution at 4 h and 24 h and scintigraphic images at 4 h were performed in normal and melanoma-bearing C57BL/6 mice. Biodistribution studies at 4 h showed tumor uptake of 99m Tc-HYNIC liposome and 99m Tc-HYNIC-PEG liposome (1.1 ± 0.6 and 2.5 ± 0.4, respectively) and also at 24 h p.i. (1.8 ± 0.5 and 3.0 ± 1.1, respectively). Scintigraphic images showed appreciable tumor uptake in melanoma tumor-bearing mice with both liposomal formulations. Our results show that 99m Tc stearyl 6-(benzylidenehydrazinyl) nicotinamide liposomes can be used as diagnostic noninvasive in vivo tumor-targeting agents capable of evaluating tumor permeability and development who can be used in personalized chemotherapy planning.

Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [ 99m Tc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [ 99m Tc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [ 99m Tc]Tc-ZHER2:V2 and [ 99m Tc]Tc-ZHER2:2395. [ 99m Tc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [ 99m Tc]Tc-ZHER2:41071 and [ 99m Tc]Tc-ZHER2:V2 was 25-30 fold lower when compared with [ 99m Tc]Tc-ZHER2:2395. The uptake in tumour and kidney for [ 99m Tc]Tc-ZHER2:41071 and [ 99m Tc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99m Tc using a GGGC chelator. The new probe, [ 99m Tc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [ 99m Tc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.

Introduction: The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is usually associated with aggressive and infiltrating breast cancer (BC) phenotype, and metastases. Functionalized silica-based nanocarriers (SiNPs) can be labeled for in vivo imaging applications and loaded with chemotherapy drugs, making possible the simultaneous noninvasive diagnosis and treatment (theranostic) for HER2-positive BC., Methods: Firstly, FITC-filled SiNPs, were engineered with two different amounts of Hc-TZ (trastuzumab half-chain) per single nanoparticle (1:2 and 1:8, SiNPs to Hc-TZ ratio), which was 99m Tc-radiolabeled at histidine residues for ex vivo and in vivo biodistribution evaluations. Secondly, nanoparticles were loaded with DOX and their in vitro and ex vivo/in vivo delivery was assessed, in comparison with liposomal Doxorubicin (Caelyx). Finally, the treatment efficacy of DOX-SiNPs-TZ (1:8 Hc-TZ) was evaluated in vivo by PET and supported by MS-based proteomics profiling of tumors., Results: SiNPs-TZ (1:8 Hc-TZ) tumor uptake was significantly greater than that of SiNPs-TZ (1:2 Hc-TZ) at 6 hours post-injection (p.i.) in ex vivo biodistribution experiment. At 24 h p.i., radioactivity values remained steady. Fluorescence microscopy, confirmed the presence of radiolabeled SiNPs-TZ (1:8 Hc-TZ) within tumor even at later times. SiNPs-TZ (1:8 Hc-TZ) nanoparticles loaded with Doxorubicin (DOX-SiNPs-TZ) showed a similar DOX delivery capability than Caelyx (at 6 h p.i.), in in vitro and ex vivo assays. Nevertheless, at the end of treatment, tumor volume was significantly reduced by DOX-SiNPs-TZ (1:8 Hc-TZ), compared to Caelyx and DOX-SiNPs treatment. Proteomics study identified 88 high stringent differentially expressed proteins comparing the three treatment groups with controls., Conclusion: These findings demonstrated a promising detection specificity and treatment efficacy for our system (SiNPs-TZ, 1:8 Hc-TZ), encouraging its potential use as a new theranostic agent for HER2-positive BC lesions. In addition, proteomic profile confirmed that a set of proteins, related to tumor aggressiveness, were positively affected by targeted nanoparticles., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Rainone et al.)

Background: Infectious diseases are one of the main causes of morbidity and mortality worldwide. Nuclear molecular imaging would be of great help to non-invasively discriminate between septic and sterile inflammation through available radiopharmaceuticals, as none is currently available for clinical practice. Here, we describe the radiolabeling procedure and in vitro and in vivo studies of 99m Tc-polymyxin B sulfate (PMB) as a new single photon emission imaging agent for the characterization of infections due to Gram-negative bacteria., Results: Labeling efficiency was 97 ± 2% with an average molar activity of 29.5 ± 0.6 MBq/nmol. The product was highly stable in saline and serum up to 6 h. In vitro binding assay showed significant displaceable binding to Gram-negative bacteria but not to Gram-positive controls. In mice, 99m Tc-HYNIC-PMB was mainly taken up by liver and kidneys. Targeting studies confirmed the specificity of 99m Tc-HYNIC-PMB obtained in vitro, showing significantly higher T/B ratios for Gram-negative bacteria than Gram-positive controls., Conclusions: In vitro and in vivo results suggest that 99m Tc-HYNIC-PMB has a potential for in vivo identification of Gram-negative bacteria in patients with infections of unknown etiology. However, further investigations are needed to deeply understand the mechanism of action and behavior of 99m Tc-HYNIC-PMB in other animal models and in humans.

Nowadays, the incidence of acute bacterial skin and skin structure infection (ABSSSI) is increasing. The increased bioavailability and reduced drug resistance of antibiotics are crucial to obtain a more effective treatment response in these infections. These favorable properties could be achieved by different drug delivery systems such as liposomes. In this study, nanosized, radiolabeled tedizolid phosphate liposomal formulations were prepared and evaluated with their in vitro cellular binding capacity and biocompatible profile for topical treatment of ABSSSI. Liposomes were characterized by evaluation of their visual inspection, particle size (about 190-270 nm), zeta potential value (around 0), and encapsulation efficiency (nearly 10%). The release rate of tedizolid phosphate from liposomes was also studied using dialysis membranes and evaluated kinetically. The stability of formulations was observed at three different temperatures and humidity conditions for 28 days. Afterward, liposomes were labeled with 99m Tc, and the optimal amount of reducing agent (stannous chloride) was determined as 500 μg in this direct labeling procedure. All liposome formulations were successfully radiolabeled with high efficiency and exhibited high radiochemical purity (> 80%) during 6 h in different media. Furthermore, the cellular bindings of liposomal formulations were evaluated in human skin fibroblast cells by measuring the radioactivity. Higher radioactivity values were obtained in CCD-1070Sk cells incubated by liposome formulations compared to sodium pertechnetate. This finding suggested that liposomal formulation increased the cellular binding of radioactivity. By the result of our study, nanosized, tedizolid phosphate encapsulated liposome formulation was found to be a favorable carrier system in the treatment of ABSSSI.

Objective: For radioactive Iodine-131 ( 131 I) treatments of thyroid diseases, increased efficacy has been reported for personalized dosimetry treatments. The measurement of Iodine-131 thyroid uptake ( 131 IU) is required in these cases. This study aims to investigate whether 99m Tc thyroid uptake ( 99m TcU) may be used in place of 131 IU for implementing personalised treatments., Methods: A retrospective study of 152 benign thyroid disease 131 I treatments was carried out during 2012-2020; 117 treatments were for female patients while 35 were for male patients diagnosed with either Graves' disease, multinodular goitre or toxic nodules., Results: A statistically significant correlation was found between 131 IU and 99m TcU data, with the data more correlated for male than female patients ( r = 0.71 vs 0.38, p -value < 0.001). Patient age and time difference between the two respective uptake measurements significantly influenced the uptake correlation in females but not for the male cohort, although there was no significant difference between the parameters across gender. Thyroid diagnosis and hormone levels showed a significant correlation with uptakes in both genders. Estimating 131 IU based on 99m TcU was shown to be predictive for male but not in female patients (R 2 = 91% vs 16%)., Conclusion: Estimating 131 IU based on 99m TcU is not recommended for females at our centre. Males reported good correlation, but a larger sample would be needed for validation., Advances in Knowledge: The initial findings showed a significant gender difference in benign thyroid uptake parameters at our centre, highlighting the potential need for gender consideration when planning 131 IU patient management and when reporting studies results.

Most epithelial tumors recruit fibroblasts and other nonmalignant cells and activate them into cancer-associated fibroblasts. This often leads to overexpression of the membrane serine protease fibroblast-activating protein (FAP). It has already been shown that DOTA-bearing FAP inhibitors (FAPIs) generate high-contrast images with PET/CT scans. Since SPECT is a lower-cost and more widely available alternative to PET, 99m Tc-labeled FAPIs represent attractive tracers for imaging applications in a larger number of patients. Furthermore, the chemically homologous nuclide 188 Re is available from generators, which allows FAP-targeted endoradiotherapy. Methods: For the preparation of 99m Tc-tricarbonyl complexes, a chelator was selected whose carboxylic acids can easily be converted into various derivatives in the finished product, enabling a platform strategy based on the original tracer. The obtained 99m Tc complexes were investigated in vitro by binding and competition experiments on FAP-transfected HT-1080 (HT-1080-FAP) or on mouse FAP-expressing (HEK-muFAP) and CD26-expressing (HEKCD26) HEK cells and characterized by planar scintigraphy and organ distribution studies in tumor-bearing mice. Furthermore, a first-in-humans application was done on 2 patients with ovarian and pancreatic cancer, respectively. Results: 99m Tc-FAPI-19 showed specific binding to recombinant FAP-expressing cells with high affinity. Unfortunately, liver accumulation, biliary excretion, and no tumor uptake were observed on planar scintigraphy for a HT-1080-FAP-xenotransplanted mouse. To improve the pharmacokinetic properties, hydrophilic amino acids were attached to the chelator moiety of the compound. The resulting 99m Tc-labeled FAPI tracers revealed excellent binding properties (≤45% binding; >95% internalization), high affinity (half-maximal inhibitory concentration, 6.4-12.7 nM), and significant tumor uptake (≤5.4% injected dose per gram of tissue) in biodistribution studies. The lead candidate 99m Tc-FAPI-34 was applied for diagnostic scintigraphy and SPECT of patients with metastasized ovarian and pancreatic cancer for follow-up to therapy with 90 Y-FAPI-46. 99m Tc-FAPI-34 accumulated in the tumor lesions, as also shown on PET/CT imaging using 68 Ga-FAPI-46. Conclusion: 99m Tc-FAPI-34 represents a powerful tracer for diagnostic scintigraphy, especially when PET imaging is not available. Additionally, the chelator used in this compound allows labeling with the therapeutic nuclide 188 Re, which is planned for the near future., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Selenium nanoparticles (SeNPs) have become one of the most prospective and promising tools in the course of cancer diagnosis and therapy. Here we describe the synthesis of a novel radioactive platform for tumor imaging using selenium nanoparticles. SeNPs were synthetized using dithionite and glutathione as reducing and capping agent respectively with 5 mmol/L sodium selenite as a precursor and then SeNPs radiolabeled with technetium-99 m, the most common and famous radioactive isotope used for imaging purposes. A characteristic profile for the synthesized SeNPs was performed including size analysis, zeta potential, antioxidant activity, radiochemical yield and in-vivo biodistribution in normal and solid tumor bearing mice. Size analysis showed amorphous SeNP cores of a mean diameter of 21 ± 5 nm with a hydrodynamic size of 43 ± 8 nm and -28 mV zeta potential. The particles also showed a superior antioxidant activity of radical scavenging activity 55.6% according to DPPH assay, in addition, satisfying radiochemical yield up to 97 ± 1.5 was achieved. In vivo studies were applied on male Swiss albino mice that demonstrated a good biodistribution pattern in normal mice with a moderate accumulation in liver at 30 min post injection. Excellent T/NT ratios were obtained in solid tumor bearing mice throughout the experimental time points. The as-synthetized selenium nanoparticles demonstrated surprising and satisfying features which make them promising enough for tumor theranosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To optimize radiolabeling with 99m Tc and 67 Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration., Material and Methods: The nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation method and coated with 4 different polymers; HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99m Tc was perfomed with 74 MBq of 99m Tc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1mg/ml) and at different times (5, 10, 15, 30 and 60minutes) and temperatures (room temperature, 40°C and 60°C). Radiolabelling with 67 Ga was perfomed by incubation of the nanoparticles with 37 MBq of 67 Gallium chloride (obtained from commercial gallium- 67 citrate) at different times (10 and 30minutes) and temperatures (room temperature, 30°C and 60°C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were perfomed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99m Tc sodium pertechnetate and 67 Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter., Results: 99m Tc labeling was carried out optimally with a tin concentration of 0.007mg/ ml for the GPM2 nanoparticles and 0.005mg / ml for the rest of the formulations, with a radiolabelling time of 10minutes at room temperature. In the case of 67 Ga the label was optimized at 30° C temperature and 30minutes of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48hours of labeling (70% nanoparticles labeled with 99m Tc and 90% those labeled with 67 Ga). Biodistribution studies of nanoparticles 99m Tc -GPM2 and 67 Ga -NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24hours after intravenous administration., Conclusion: The labeling procedure with 99m Tc and 67 Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies., (Copyright © 2020 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have displayed multifunctional applications in cancer theranostics following systemic delivery. In an effort to increase the therapeutic potential of local therapies (including focal hyperthermia), nanoparticles can also be administered intratumorally. Therefore, the development of a reliable pharmacokinetic model for the prediction of nanoparticle distribution for both clinically relevant routes of delivery is of high importance., Materials and Methods: The biodistribution of SPIONs (of two different sizes - 130 nm and 60 nm) radiolabeled with zirconium-89 or technetium-99m following intratumoral or intravenous injection was investigated in C57/Bl6 mice bearing subcutaneous GL261 glioblastomas. Based on PET/CT biodistribution data, a novel pharmacokinetic model was established for a better understanding of the pharmacokinetics of the SPIONs after both administration routes., Results: The PET image analysis of the nanoparticles (confirmed by histology) demonstrated the presence of radiolabeled nanoparticles within the glioma site (with low amounts in the liver and spleen) at all investigated time points following intratumoral injection. The mathematical model confirmed the dynamic nanoparticle redistribution in the organism over a period of 72 h with an equilibrium reached after 100 h. Intravenous injection of nanoparticles demonstrated a different distribution pattern with a rapid particle retention in all organs (particularly in liver and spleen) and a subsequent slow release rate., Conclusion: The mathematical model demonstrated good agreement with experimental data derived from tumor mouse models suggesting the value of this tool to predict the real-time pharmacokinetic features of SPIONs in vivo. In the future, it is planned to adapt our model to other nanoparticle formulations to more precisely describe their biodistribution in in vivo model systems., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (© 2020 Klapproth et al.)

Purpose: The aim of the study was to evaluate the ability of technetium-99m-fucoidan ([ 99m Tc]fucoidan), a molecular imaging agent specific for selectins, in the assessment of early localized immunity in a rat model of experimental autoimmune myocarditis (EAM)., Procedures: EAM was induced in Lewis rats and troponin T; brain natriuretic peptide (BNP) and anti-myosin antibodies were measured in plasma. Separately, [ 99m Tc]fucoidan single-photon emission computed tomography (SPECT)/x-ray computed tomography (CT) was performed in the very early phase of myocarditis at 10, 15, and 21 days after immunization. Then, hearts were collected and used for autoradiography, well counting, histology, and flow cytometry analysis., Results: The EAM acute phase is characterized by extensive myocardial necrosis, release of troponin and BNP, and pericardial effusion. [ 99m Tc]Fucoidan uptake was significantly increased in EAM compared with controls starting from D15. There was a close relationship between uptake of the tracer and myocardial content in CD45+, CD8+, CD11b+, and CD31+ cells., Conclusions: [ 99m Tc]Fucoidan SPECT/CT accurately diagnosed the autoimmune attack in the early steps of EAM and could be used to monitor disease evolution and therapy efficiency.

Pancreatic cancer has a high mortality rate and efforts towards diagnosis and therapy at an early stage are particularly appealing. Recently, a small peptide, BBN7-14, has attracted much attention for its specific binding ability to gastrin releasing peptide receptor (GRPR), which is highly overexpressed in various types of cancer, including pancreatic cancer. However, its poor stability in vivo restricts its direct clinical application. Herein, by rational design and transformation of BBN7-14, a novel six-amino acid peptide, GB-6, which maintains a specific GRPR-binding feature and exhibits enhanced stability in vitro and in vivo, was designed. Competitive binding with BBN7-14 and cellular uptake related to GRPR expression levels verified the specific affinity of GB-6 to GRPR. Additionally, this novel peptide was conjugated with near-infrared dye and the radionuclide 99mTc for pancreatic cancer diagnosis in cells and in vivo. Surprisingly, despite having the same cellular affinity as BBN7-14, GB-6 showed much higher pancreatic cancer-targeting ability than BBN7-14 by both fluorescence imaging and radionuclide imaging. It was proven that this strange phenomenon was attributed to the distinct in vivo stability of GB-6 and its more favorable pharmacokinetic properties and metabolic stability relative to BBN7-14. Altogether, this novel peptide GB-6, with GRPR-targeting ability and enhanced stability, is a more promising candidate for the clinical diagnosis of pancreatic cancer.

Previously, we reported the preparation and preclinical studies of 99m Tc-labeled gold nanoparticles-mannose ( 99m Tc-AuNP-mannose) with potential for sentinel lymph node (SLN) detection by using nuclear medicine procedures. This study aimed to evaluate the biokinetics and hybrid (2D/3D) dosimetry of 99m Tc-AuNP-mannose in five patients with breast cancer under a sentinel lymph node detection protocol. Anterior and posterior whole-body planar images (2D, at 0.5, 2, 6, and 24 h) and single-photon emission computed tomography (3D at 6.5 h)/computed tomography (SPECT/CT) images were acquired after 99m Tc-AuNP-mannose administration (37 MBq). Through a hybrid quantification method, activity in tissues of interest at the different acquisition times was determined and integrated over time to obtain the total nuclear transformations ( N ), as well as the mean residence time, in each tissue. N values and the OLINDA code were used for estimating the internal radiation absorbed doses. Results demonstrated that 99m Tc-AuNP-mannose successfully accumulates and remains up to 24 h in the sentinel lymph node without detectable migration to other lymph nodes and no side effects on patients. Negligible absorption of the radiolabeled nanoparticles into the circulatory system was observed, from which the radio-nanosystem is rapidly eliminated by kidneys. Hybrid (2D/3D) dosimetry evaluations showed equivalent doses to SLN, breast, and kidneys of 172.34, 5.32, and 0.08 mSv/37 MBq, respectively, with an effective dose of 2.05 E  - 03 mSv/MBq. The mean effective residence time in SLN was 0.92 h. This preliminary study indicates that the use of 99m Tc-AuNP-mannose for successful SLN detection in patients is safe, producing an effective dose at the level recommended for diagnostic studies (<10 mSv)., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Gerardo Ramírez-Nava et al.)

Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of 99m Tc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA- 99m Tc-6-hydrazinylnicotinyl]-Arg-NaI-Gly) as a SPECT radioligand capable of specifically detecting the CXCR4 protein. This research aimed to estimate the biokinetic behavior and radiation dosimetry of 99m Tc-CXCR4-L in healthy subjects, as well as to correlate the radiotracer uptake by brain tumors in patients, with the histological grade of differentiation and CXCR4 expression evaluated by immunohistochemistry. 99m Tc-CXCR4-L was obtained from freeze-dried kits prepared under GMP conditions (radiochemical purities >97%). Whole-body scans from six healthy volunteers were acquired at 0.3, 1, 2, 4, 6, and 24 h after 99m Tc-CXCR4-L administration (0.37 GBq). Time-activity curves of different source organs were obtained from the image sequence to adjust the biokinetic models. The OLINDA/EXM code was employed to calculate the equivalent and effective radiation doses. Nine patients with evidence of brain tumor injury (6 primaries and 3 recurrent), determined by MRI, underwent cerebral SPECT at 3 h after administration of 99m Tc-CXCR4-L (0.74 GBq). Data were expressed as a T / B (tumor uptake/background) ratio. Biopsy examinations included histological grading and anti-CXCR4 immunohistochemistry. Results showed a fast blood activity clearance ( T 1/2 α  = 0.81 min and T 1/2 β  = 12.19 min) with renal and hepatobiliary elimination. The average equivalent doses were 6.10 E  - 04, 1.41 E  - 04, and 3.13 E  - 05 mSv/MBq for the intestine, liver, and kidney, respectively. The effective dose was 3.92 E  - 03 mSv/MBq. SPECT was positive in 7/9 patients diagnosed as grade II oligodendroglioma (two patients), grade IV glioblastoma (two patients), grade IV gliosarcoma (one patient), metastasis, and diffuse astrocytoma with T / B ratios of 1.3, 2.3, 13, 7, 19, 5.5, and 3.9, respectively, all of them with positive immunohistochemistry. A direct relationship between the grade of differentiation and the expression of CXCR4 was found. The two negative SPECT studies showed negative immunohistochemistry with a diagnosis of reactive gliosis. This "proof-of-concept" research warrants further clinical studies to establish the usefulness of 99m Tc-CXCR4-L in the diagnosis and prognosis of brain tumors., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Paola Vallejo-Armenta et al.)

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 99m Tc-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., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Breast cancer is the most common type of cancer in women worldwide. There have been many efforts for early breast cancer detection and among them molecular imaging have been extremely of high importance. Single-photon emission computed tomography (SPECT/CT) is a kind of imaging technique able to reveal crucial information with using radiopharmaceuticals. In this study, Technetium-99m-(DOTA-NHS-ester)-Methionine radiopharmaceutical was synthesized. Between 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-HNS ester) (MACROCYCLICS, DOTA-NHS ester, Plano, Texas, USA) and methionine(marker) were conjugated. The DOTA-HNS ester-Methionine was labeled with Technetium-99m (Inter-Medical, Technetium-99m, Bergamo, Italy). The synthesized radiopharmaceutical was used in SPECT/CT imaging for breast cancer diagnosis. For radiopharmaceutical evaluation, MTT assay for cellular toxicity, biodistribution, cellular uptake and radiochemical purity were employed.Technetium-99m-(DOTA-NHS-ester)-Methionine radiochemical had less cellular toxicity in human embryonic kidney cells 293 cell line (HEK293). Cellular uptake was indicated higher percent with use of Methionine as a marker, and radiochemical purity was high. Based on the results Technetium-99m-(DOTA-NHS-ester)-Methionine radiochem may be a better option for early detection of breast cancer. Further study is recommended to confirm these findings in clinical practice., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: Prostate cancer is a serious threat to men's health so it is necessary to develop technics for early detection of this malignancy. The purpose of this research was the evaluation of a new 99m Tc-labeled GnRH analogue as an imaging probe for tumor targeting of prostate cancer., Methods: 99m Tc-labeled-DLys6-GnRH analogue was prepared based on HYNIC as a chelating agent and tricine/ EDDA as coligands for labeling with 99m Tc. HYNIC was coupled to epsilon amino group of DLys6 through aminobutyric acid (GABA) as a linker. Radiochemical purity and stability in normal saline and serum, were determined by TLC and HPLC methods. Furthermore, calculation of protein-binding and partition coefficient constant were carried out for 99m Tc labeled peptide. The cellular experiments including receptor binding specificity and affinity were studied using three prostate cancer cell lines LN-CaP, DU-145 and PC-3. Finally, the animal assessment and SPECT imaging of radiolabeled GnRH analogue were evaluated on normal mice and nude mice bearing LN-CaP tumor., Results: The GnRH conjugate was labeled with high radiochemical purity (~97%). The radiolabeled peptide showed efficient stability in the presence of normal saline and human serum. The in vitro cellular assays on three prostate cancer cell lines indicated that the radiotracer was bound to LN-CaP cells with higher affinity compared to DU-145 and PC-3 cells. The Kd values of 99m Tc- HYNIC (tricine/ EDDA)-Gaba-D-Lys6GnRH were 89.39±26.71, 93.57±30.49 and107.3±18.82 in LN-CaP, PC-3 and DU-145 cells respectively. The biodistribution studies in normal mice and LN-CaP tumor-bearing nude mice showed similar results including rapid blood clearance and low radioactivity accumulation in non-target organs. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor uptake was 1.72±0.45 %ID/g at 1h p.i. decreasing to 0.70±0.06%ID/g at 4h p.i. for 99m Tc-HYNIC-Gaba-D-Lys6GnRH. The maximum tumor/ muscle ratio was 2.30 at 1h p.i. Pre-saturation of receptor using an excess of unlabeled peptide revealed that the tumor uptake was receptor mediated. The results of the SPECT image of LN-CaP tumor were in agreement with the biodistribution data., Conclusion: Based on this study, we suggest LN-CaP as a favorable cell line for in vivo studies on GnRH analogues. Moreover, this report shows that 99m Tc-HYNIC (tricine/EDDA)-Gaba-D-Lys6GnRH may be a suitable candidate for further evaluation of prostate cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: The epidermal growth factor receptor (EGFR) signaling pathway is widely recognized to play an important role in development and progression of many malignant tumors, including lung cancer. The aim of this study was to produce a useful technetium-99m ( 99m Tc) complex for early detection and staging of EGFR-positive tumors. Methods: The authors labeled quinazoline derivative (3-iodinephenyl) quinazoline-4, 6-diamine with 99m Tc using S-acetylmercaptoacetyltriglyglycinate (MAG 3 ) conjugated to quinazoline derivative through 4-[(2-aminoethyl)amino]-4-oxobut-2-enoic acid because it is a bifunctional chelator with an average yield of 93.9% ± 2.5% and radiochemical purity of >98%. Results: In vitro studies indicate that the [ 99m Tc]-complex 13 has high stability in physiological conditions and binds the HCC 827 cells and shows HCC 827 internalization. The biodistribution of the [ 99m Tc]-complex 13 in healthy Institute of Cancer Research mice indicates the rather fast blood clearance through the hepatobiliary system. Conclusion: These preliminary results pave the road for estimating the status of EGFR and monitoring the response to EGFR tyrosine kinase inhibitors as a personalized cancer therapy regimen.

Cystic fibrosis (CF) disease is caused by mutations affecting the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel expressed in the mucosal side of epithelial tissue. In the airway, dysfunctional CFTR results in a transepithelial osmotic imbalance leading to hyperabsorption of airway surface liquid mucostasis, chronic inflammation, and eventual respiratory failure. Human nasal epithelial cell cultures from healthy and CF donors were used to perform studies of liquid and solute transport dynamics at an air/liquid interface in order to emulate the in vivo airway. Then, these results were used to inform a quantitative systems pharmacology model of airway epithelium describing electrically and chemically driven transcellular ionic transport, contributions of both convective and diffusive paracellular solute transport, and osmotically driven transepithelial water dynamics. Model predictions showed CF cultures, relative to non-CF ones, have increased apical and basolateral water permeabilities, and increase paracellular permeability and transepithelial chemical driving force for a radiolabeled tracer used to track small molecule absorption. These results provide a computational platform to better understand and probe the mechanisms behind the liquid hyperabsorption and small molecule retention profiles observed in the CF airway.

Bio-based synthesis of Nano-Ceria (NC) was performed in Linum usitatissimum L. (Lu) seeds extract as capping agent. Obtained gel was calcined at 400, 500, and 600 °C to investigate the effect of temperature on the size and morphology of the particles. All samples had spherical morphology which their crystallite size was decreased in higher temperature. Products were characterized by TGA/DTA, UV-vis, FESEM, FTIR and XRD. The band gap of the prepared samples was calculated through Tauc plot in the range of 3.2-3.4 eV. The results of MTT assay confirmed that NC has been shown no significant toxicity on A549 cell line. 2',7'-dichlorofluorescin diacetate (DCFDA) was used to determine antioxidant properties of NC on A549 cell and the results showed that all concentrations of NC could reduce reactive oxygen species (ROS). NC was labeled with technetium ( 99m Tc) for in vivo bio-distribution study in Wistar rat. Radiolabeled NC was stable in different environments of PBS buffer and human serum with radiochemical purity of more than 95% according to the instant thin layer chromatography (ITLC) method. DLS analysis showed radiolabeled particles had small size and pleasant colloidal stability. Bio-distribution of radiolabeled NC illustrated the highest accumulation in kidneys (1 h: 5.94 ± 0.77%ID/g, 4 h: 10.95 ± 5.99%ID/g, 24 h 7.94 ± 0.36%ID/g). Moreover, low uptake of 99m Tc-NC in stomach confirmed the in vivo stability of 99m Tc-NC. Accordingly, NC could be a worthy candidate for biological purposes and in vivo studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The human epidermal growth factor receptor 2 (HER2) represents one of the most studied tumor-associated antigens for cancer immunotherapy. The receptors for HER2 are overexpressed in various human cancers, such as breast and ovarian cancer. The relatively low expression of this antigen on normal tissues makes it a clinically useful molecular target for tumor imaging and targeted therapy. HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcomes. Thus, HER2 has become an important prognostic and predictive factor, as well as a potential molecular target. Due to the heterogeneity of breast cancer and possible discordance in HER2 status between primary tumors and distant metastases, assessment of HER2 expression by noninvasive imaging is important. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in the selection of an optimal therapy. Another tumor-specific antigen is MUC1, which is silent on normal tissues, but overexpressed in almost all human epithelial cell cancers, including >90% of human breast, ovarian, pancreatic, colorectal, lung, prostate, and gastric cancers and is a promising tumor antigen with diagnostic as well as the therapeutic potential of cancer. Radiolabeled small peptide ligands are attractive as probes for molecular imaging, as they reach and bind the target receptor efficiently and clear from blood and non-target organs faster than bulky antibodies. In this study, HER2 and MUC1-based peptides were synthesized and preclinically evaluated in an effort to develop peptide-based SPECT radiopharmaceuticals derived from tumor-associated antigens for the detection of breast cancer. Our findings demonstrate that the tumor antigen peptides radiolabeled efficiently with 99m Tc and showed high metabolic stability in human plasma in vitro. The data from breast tumor cell binding confirmed the high affinity (in low nanomolar range) towards respective breast cancer cell lines. In healthy mice, 99m Tc-labeled peptides displayed favorable pharmacokinetics, with high excretion by the renal system. In tumor xenografts nude mice models, good uptake by the SKBR3, MCF7, and T47D tumors were found, with good tumor-to-blood and tumor to muscle ratios. Additionally, tumor lesions can be seen in γ-camera imaging. Our data suggest that based on its ability to detect HER2- and MUC1-positive breast cancer cells in vivo, 99m Tc-HER2 and 99m Tc-MUC1-targeted peptides may be promising tumor imaging probes and warrant further investigation.

Roxithromycin is a second-generation macrolide antibiotic derived from erythromycin. In the current study, roxithromycin (ROX) was successfully labeled with technetium-99m for early diagnosis of bacterial infection and discrimination between septic and aseptic inflammation. The highest radiochemical purity of ≥95% was achieved by investigating different labeling parameters such as pH, ligand/reducing agent concentration, temperature, and amount of stabilizing agent. For this purpose, 0.3-0.5 mg ligand, 2-6 μg SnCl 2 ·2H 2 O as a reducing agent at basic pH (8-10 pH) and 2 mg mannitol used as a stabilizing agent, in the end, 370 MBq 99m Tc added into the reaction vials and incubated for a wide range of temperature (-4 to 65°C). The percent radiochemical purity of 99m Tc-roxithromycin was assessed with the help of the radio-thin-layer chromatography technique. The characterization studies were carried out using electrophoresis and Radio-HPLC techniques as well as saline stability and serum stability studies were also performed. Furthermore, biodistribution study was also performed in an inflamed animal model to discriminate between septic (heat-killed Staphylococcus aureus) and aseptic (turpentine oil) inflammatory lesions. The results were elaborated that 99m Tc-roxithromycin ( 99m Tc-ROX) was clearly bounded at the septic inflammation site (T/NT ratio of 7.08 ± 1.14) at 30 min postadministration, and maximum accumulation was seen in heart, lungs, liver, stomach, kidneys, and intestine. The results were suggested that 99m Tc-ROX might be used to discriminate between septic and aseptic inflammatory lesions at an early stage., (© 2018 John Wiley & Sons A/S.)

Objective: 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 ( 99m Tc) labeled lapachol as an imaging probe for breast cancer identification., Methods: To achieve this purpose, lapachol was labeled with 99m Tc, radiochemical purity and in vitro stability were determined. Blood clearance, in healthy mice, and biodistribution, in 4T1 tumor-bearing mice, were also evaluated., Results: Lapachol was successfully labeled with 99m Tc, with high values of radiochemical yield (95.9±3.4%). In vitro stability showed that the radiolabeled complex remained stable for up to 24h, 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 50.0min, 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 24h after administration., Conclusion: These findings suggest that 99m Tc-lapachol can be a potential diagnostic agent for breast tumors., (Copyright © 2019 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Designed ankyrin repeat proteins (DARPins) are small engineered scaffold proteins that can be selected for binding to desirable molecular targets. High affinity and small size of DARPins render them promising probes for radionuclide molecular imaging. However, detailed knowledge on many factors influencing their imaging properties is still lacking. We have evaluated two human epidermal growth factor 2 (HER2)-specific DARPins with different size and binding properties. DARPins 9&#95;29-H 6 and G3-H 6 were radiolabeled with iodine-125 and tricarbonyl technetium-99m and evaluated in vitro. A side-by-side comparison of biodistribution and tumor targeting was performed. HER2-specific tumor accumulation of G3-H 6 was demonstrated. A combination of smaller size and higher affinity resulted in a higher tumor uptake of G3-H 6 in comparison to 9&#95;29-H 6 . Technetium-99m labeled G3-H 6 demonstrated a better biodistribution profile than 9&#95;29-H 6 , with several-fold lower uptake in liver. Radioiodinated G3-H 6 showed the best tumor-to-organ ratios. The combined effect of affinity, molecular weight, scaffold composition, and nonresidualizing properties of iodine label provided radioiodinated G3-H 6 with high clinical potential for imaging of HER2.

Purpose: Technetium-99m ( 99m Tc) is the radioisotope most widely used in diagnostic nuclear medicine. It is readily available from 99 Mo/ 99m Tc generators as the β - decay product of the 99 Mo (T &frac12;  = 66 h) parent nuclide. This latter is obtained as a fission product in nuclear reactors by neutron-induced reactions on highly enriched uranium. Alternative production routes, such as direct reactions using proton beams on specific target materials [ 100 Mo(p,2n) 99m Tc], have the potential to be both reliable and relatively cost-effective. However, results showed that the 99m Tc extracted from proton-bombarded 100 Mo-enriched targets contains small quantities of several Tc radioisotopes ( 93m Tc, 93 Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc, and 97m Tc). The aim of this work was to estimate the dose increase (DI) due to the contribution of Tc radioisotopes generated as impurities, after the intravenous injection of four radiopharmaceuticals prepared with cyclotron-produced 99m Tc (CP- 99m Tc) using 99.05% 100 Mo-enriched metallic targets., Methods: Four 99m Tc radiopharmaceuticals (pertechnetate, sestamibi (MIBI), hexamethylpropylene-amine oxime (HMPAO) and disodium etidronate (HEDP)) were considered in this study. The biokinetic models reported by the International Commission on Radiological Protection (ICRP) for each radiopharmaceutical were used to define the main source organs and to calculate the number of disintegrations per MBq that occurred in each source organ (N source ) for each Tc radioisotope present in the CP- 99m Tc solution. Then, target organ equivalent doses and effective dose were calculated for each Tc radioisotope with the OLINDA/EXM software versions 1.1 and 2.0, using the calculated N source values and the adult male phantom as program inputs. Total effective dose produced by all Tc isotopes impurities present in the CP- 99m Tc solution was calculated using the fraction of total activity corresponding to each radioisotope and compared with the effective dose delivered by the generator-produced 99m Tc., Results: In all cases, the total effective DI of CP- 99m Tc radiopharmaceuticals calculated with either versions of the OLINDA software was less than 10% from 6 up to 12 h after EOB. 94m Tc and 93m Tc are the Tc radioisotopes with the highest concentration in the CP- 99m Tc solution at EOB. However, their contribution to DI 6 h after EOB is minimal, due to their short half-lives. The radioisotopes with the largest contribution to the effective DI are 96 Tc, followed by 95 Tc and 94 Tc. This is due to the types of their emissions and relatively long half-lives, although their concentration in the CP- 99m Tc solution is five times lower than that of 94m Tc and 93m Tc at the EOB., Conclusions: The increase in the radiation dose caused by other Tc radioisotopes contained in CP- 99m Tc produced as described here is quite low. Even though the concentrations of the 94 Tc and 95 Tc radioisotopes in the CP- 99m Tc solution exceed the limits established by the European Pharmacopoeia, CP- 99m Tc radiopharmaceuticals could be used in routine nuclear medicine diagnostic studies if administered from 6 to 12 h after the EOB, thus maintaining the effective DI within the 10% limit., (© 2019 American Association of Physicists in Medicine.)

In this study, we developed, characterized, and tested in vivo polymeric nanoparticle of ethambutol labeled with 99mTc as nanoradiopharmaceutical for early diagnosis of tuberculosis by single-photon emission computed tomography, also as a therapeutic choice. Nanoparticles were developed by double emulsification. All characterization tests were performed, as scanning electron microscopy and dynamic light scattering. The labeling process with 99mTc was performed using the direct labeling process. In vitro and in vivo assays were performed with animals and cells. The results showed that a spherical ethambutol nanoparticle with a size range of 280-300 nm was obtained. The stability test showed that the nanoparticles were well labeled with 99mTc (> 99.1%) and keep labeled over 24 h. The biodistribution assay showed that almost 18% of the nanoparticles were uptake by the lung in infected mice (male C57Bl/6) with Mycobacterium bovis BCG (4 × 10 5  CFU/cavity), corroborating its use as a nanodrug for tuberculosis imaging. The results for the cell assay corroborate its therapeutical effect. We developed and efficiently tested a new nanodrug that can be used for both imaging and therapy of tuberculosis, acting as a novel nanotheranostic.

Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [ 99m Tc(CO) 3 (H 2 O) 3 ]+ radiolabeled glycylglycine (GlyGly)., Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex ( 99m Tc(CO) 3 -Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging., Results: The high radiolabelling yield of 99m Tc(CO) 3 -GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal., Conclusion: This study shows that 99m Tc(CO) 3 -GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99m Tc(CO) 3 -GlyGly can be performed on tumor-bearing animals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Solid Lipid Nanoparticles (SLNs) possess unique in vivo features such as high resistivity, bioavailability, and habitation at the target site. Coating nanoparticles with polymers such as chitosan greatly affects their pharmacokinetic behavior, stability, tissue uptake, and controlled drug delivery. The aim of this study was to prepare and evaluate the biodistribution of 99mTc-labeled SLNs and chitosan modified SLNs in mice., Methods: 99mTc-oxine was prepared and utilized to radiolabel pre-papered SLNs or chitosan coated SLNs. After purification of radiolabeled SLNs (99mTc-SLNs) and radiolabeled chitosan-coated SLNs (99mTc-Chi-SLNs) using Amicon filter, they were injected into BALB/c mice to evaluate their biodistribution patterns. In addition, nanoparticles were characterized using Transmission Electron Microscopy (TEM), Fourier-transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRD) and Dynamic Light Scattering (DLS)., Results: 99mTc-oxine with high radiochemical purity (RCP~100%) and stability (RCP > 97% at 24 h) was used to provide 99mTc-SLNs and 99mTc-Chi-SLNs with high initial RCP (100%). TEM image and DLS data suggest 99mTc- SLNs susceptibility to aggregation. To that end, the main portion of 99mTc-SLNs radioactivity accumulates in the liver and intestines, while 99mTc-Chi-SLNs sequesters in the liver, intestines and kidneys. The blood radioactivity of 99mTc-Chi-SLNs was higher than that of 99mTc-SLNs by 7.5, 3.17 and 3.5 folds at 1, 4 and 8 h post-injection. 99mTc- Chi-SLNs uptake in the kidneys in comparison with 99mTc-SLNs was higher by 37.48, 5.84 and 11 folds at 1, 4 and 8h., Conclusion: The chitosan layer on the surface of 99mTc-Chi-SLNs reduces lipophilicity in comparison with 99mTc- SLNs. Therefore, 99mTc-Chi-SLNs are less susceptible to aggregation, which leads to their lower liver uptake and higher kidney uptake and blood concentration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

[ 99m Tc][TcN-DBODC(5) is the lead candidate of a class of cationic complexes proposed as myocardial imaging agents (MPIAs). Phase I clinical studies showed that its clinical properties were comparable to those of the commercially available agents. Thus, modification of [ 99m Tc]TcN-DBODC(5), directed to obtain an ideal myocardial imaging without interference from the adjacent organ activities, is desirable. This work describes the pharmacological and pharmacokinetic development of four new complexes of general formula [ 99m Tc][Tc(N)(DASD)(PNP n)] + , [ 99m Tc]TcN-DASD( n) (DASD = 1,4-dioxa-8-azaspiro[4,5]decandithiocarbamate; PNP n = bisphosphinoamine), proposed as improved MPIAs. Among the tested compounds, [ 99m Tc]TcN-DASD(5) and [ 99m Tc]TcN-DASD(7) showed enhanced heart uptake compared with the gold standards, with a rapid liver washout and superior heart-to-liver ratio. These features might shorten the duration of imaging procedures below 30 min, consenting the early acquisition of high-quality images. In addition, mechanistic studies were performed in cellulo by using human drug-sensitive and drug-resistant cancer cell lines, obtaining results which might be conveniently applied to tumor imaging.

Hydroponic uptake studies were conducted to evaluate the uptake and translocation of Tc, Cs (stable analog for Cs), Np, and U into established and seedling Andropogon virginicus specimens under controlled laboratory conditions. Plant specimens were grown in analyte-spiked Hoagland nutrient solution for 24 h, 3 d, and 5 d. Translocation to shoots was greatest for Tc and Cs, likely due to their analogous nature to plant nutrients, while U (and Np to a lesser extent) predominantly partitioned to root tissue with less extensive translocation to the shoots. Plant age contributed significantly to differences in concentration ratios for all nuclides in shoot tissues (p ≤ 0.024), with higher concentration ratios for seedling specimens. Additionally, duration of exposure was associated with significant differences in concentration ratios of Cs and Tc for seedlings (p = 0.007 and p = 0.030, respectively) while plant part (root or shoot) was associated with significant differences in concentration ratios of established plants (p < 0.001 for both nuclides). Statistically significant increases in radionuclide uptake in seedling specimens relative to established plants under controlled conditions suggests that, in addition to geochemical factors, plant life stage of wild grasses may also be an important factor influencing radionuclide transport in the natural environment.

Background: The sentinel node (SN) detection by dual tracer method using indocyanine green (ICG) and a radioisotope (RI) has been recommended for early gastric cancer. However, institutions are limited due to radioactivity in the RI method. The greatest advantage of the RI method is that it objectively assesses RI uptake as a numerical value. The aim of the present study was to verify the usefulness of ICG fluorescence intensity in SN., Methods: Seventeen patients with early gastric cancer were enrolled in this study. RI uptake by each lymph node was measured using Navigator GPS and fluorescence nodes were identified using the hyper eye medical system (HEMS). Fluorescence intensity in fluorescence nodes was evaluated using ICG intensity imaging software (Mizuho, Japan) of the HEMS., Results: The total number of dissected lymph nodes was 227, with an average of 13.3 per patient. The numbers of HN, FN-S, and FN-B were 64, 77, and 34. RI uptake was significantly greater by FN-S than by non-FN-S (P = 0.0016). The median fluorescence intensity value was higher in HN than in non-HN (P < 0.001). A correlation was observed between RI uptake and fluorescence intensity. Dissecting FNs with fluorescence intensity levels of 1-6 resulted in 92.1% dissection of HNs., Conclusion: It is possible that the evaluation of fluorescence intensity is useful for selected SNs instead of RI tracer. If fluorescence intensity is measurable in surgery, an infrared fluorescence method using ICG may be useful and safe for the detection of SN in early gastric cancer.

Introduction: Nowadays, molecular imaging radiopharmaceuticals', nanoparticles', and/or small-molecule biomarkers' applications are increasing rapidly worldwide. Thus, researchers focus on providing the novel, safe, and cost-effective ones., Materials and Methods: In the present experiment, technetium-99m ( 99m Tc)-labeled PEG-citrate dendrimer-G 2 conjugated with glutamine (nanoconjugate) was designed and assessed as a novel tumor imaging probe both in vitro and in vivo. Nanoconjugate was synthesized and the synthesis was confirmed by Fourier transform infrared, proton nuclear magnetic resonance, liquid chromatography-mass spectrometry, dynamic light scattering, and static light scattering techniques. The toxicity was assessed by XTT and apoptosis and necrosis methods., Results: Radiochemical purity indicates that the anionic dendrimer has a very high potential to complex formation with 99m Tc and is also very stable in the human serum in different times. Results from the imaging procedures showed potential ability of nanoconjugates to detect tumor site., Conclusion: Suitable features of the anionic dendrimer show that it is a promising agent to improve nanoradiopharmaceuticals., Competing Interests: Disclosure The authors report no conflict of interest in this work.

In this study, a d-glucosamine derivative with an isonitrile group (CN5DG) was synthesized and it was chosen to coordinate with 99m Tc for preparing 99m Tc-CN5DG. 99m Tc-CN5DG could be readily obtained with high radiochemical purity (>95%) and had great in vitro stability and metabolic stability in urine. The radiotracer demonstrated a positive response to the administration of glucose and insulin in S180 and A549 tumor cells in vitro, suggesting the mechanism of 99m Tc-CN5DG into tumor cells was related to glucose transporters. Biodistribution studies in mice bearing A549 xenografts showed 99m Tc-CN5DG had a high tumor uptake and high tumor-to-background ratios. SPECT/CT images further supported its ability for tumor imaging. As a cheap, conveniently made and widely available probe, 99m Tc-CN5DG would become a potential "working horse" and be a breakthrough in 99m Tc-labeled radiopharmaceuticals for tumor detection.

With the aim to prepare hypoxia tumor imaging agents, technetium(I) and rhenium(I) tricarbonyl complexes with dipyridylamine (L1 = N-{[1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-1,2,3-triazol-4-yl]methyl}-N-(2-pyridinylmethyl)-2-pyridinemethanamine; L3 = N-{[1-[N-(4-aminosulfonylphenyl)]-1H-1,2,3-triazol-4-yl]methyl}-N-(2-pyridinyl-methyl)-2-pyridinemethanamine), and iminodiacetate (H 2 L2 = N-{[1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-1,2,3-triazole-4-yl]methyl}-N-(carboxy-methyl)-glycine; H 2 L4 = N-{[1-[N-(4-aminosulfonylphenyl)]-1H-1,2,3-triazole-4-yl]methyl}-N-(carboxymethyl)-glycine) ligands appended to sulfonamide or sulfocoumarin carbonic anhydrase inhibitors were synthesized. The Re(I) complexes were characterized using 1 H/ 13 C NMR, MS, EA, and in one case the X-ray structure of [Et 3 NH][Re(CO) 3 (L2)] was obtained. As expected, the Re coordination geometry is distorted octahedral, with a tridentate iminodiacetate ligand in a fac arrangement dictated by the three strong-field CO ligands. Inhibition studies of human carbonic anhydrases (hCAs) showed that the Re sulfocoumarin derivatives were inactive against hCA-I, -II and -IV, but had moderate affinity for hCA-IX. The Re sulfonamides showed improved affinity against all tested hCAs, with [Re(CO) 3 (L4)] - being the most active and selective for the hCA-IX isoform. The corresponding 99m Tc complexes were synthesized from fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + , purified by HPLC, and obtained with average 41-76% decay-corrected radiochemical yields and with >99% radiochemical purity. Uptake in HT-29 tumors at 1 h post-injection was highest for [ 99m Tc(CO) 3 (L4)] - (0.14 ± 0.10%ID/g) in comparison to [ 99m Tc(CO) 3 (L1)] + (0.06 ± 0.01%ID/g), [ 99m Tc(CO) 3 (L2)] - (0.03 ± 0.00%ID/g), and [ 99m Tc(CO) 3 (L3)] + (0.07 ± 0.03%ID/g). The uptake in tumors was further reduced at 4 h post-injection. For potential imaging application with single photon emission computed tomography, further optimization is needed to improve the affinity to hCA-IX and uptake in hCA-IX expressing tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The obstructive renal radioactivity after injection of antibody fragments/constructs labeled with metallic radionuclides would be improved by liberating a radiometal chelate of urinary excretion from the antibody molecules by enzymes on the renal brush border membrane (BBM). A tripeptide GFK sequence was newly evaluated as an enzyme-cleavable linkage and conjugated to a 99m Tc chelate of an isonicotinic acid derivative of 2-picolylglycine ( 99m Tc-IPG). 99m Tc-IPG-glycine was liberated from 99m Tc-IPG-GFK by the enzymes, while 99m Tc-IPG-GK (where the tripeptide GFK was substituted with a dipeptide GK) did not. When injected into mice, 99m Tc-IPG-GFK-conjugated Fab exhibited lower renal radioactivity levels than directly radioiodinated Fab shortly after injection without reducing the tumor radioactivity levels, due to a release and excretion of 99m Tc-IPG-glycine by enzymes present on the renal BBM. These findings would provide insights to develop antibody fragments/constructs labeled with metallic radionuclides of the clinical relevance for improved renal radioactivity levels.

High expression of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal carcinomas is a predictive biomarker for treatment using HER2-targeted therapeutics (antibodies trastuzumab and pertuzumab, antibody-drug conjugate trastuzumab DM1, and tyrosine kinase inhibitor lapatinib). Radionuclide molecular imaging of HER2 expression might permit stratification of patients for HER2-targeting therapies. In this study, we evaluated a new HER2-imaging probe based on the designed ankyrin repeat protein (DARPin) 9&#95;29. DARPin 9&#95;29 was labeled with iodine-125 by direct radioiodination and with [ 99m Tc]Tc(CO) 3 using the C-terminal hexahistidine tag. DARPin 9&#95;29 preserved high specificity and affinity of binding to HER2-expressing cells after labeling. Uptake of [ 125 I]I-DARPin 9&#95;29 and [ 99m Tc]Tc(CO) 3 -DARPin 9&#95;29 in HER2-positive SKOV-3 xenografts in mice at 6 h after injection was 3.4 ± 0.7 %ID/g and 2.9 ± 0.7 %ID/g, respectively. This was significantly ( p < 0.00005) higher than the uptake of the same probes in HER2-negative Ramos lymphoma xenografts, 0.22 ± 0.09 %ID/g and 0.30 ± 0.05 %ID/g, respectively. Retention of [ 125 I]I-DARPin 9&#95;29 in the lung, liver, spleen, and kidneys was appreciably lower compared with [ 99m Tc]Tc(CO) 3 -DARPin 9&#95;29, which resulted in significantly ( p < 0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by SPECT/CT imaging. In conclusion, radioiodine is a preferable label for DARPin 9&#95;29.

Epirubicin is an antineoplastic agent of anthracycline antibiotic, used for treating a variety of tumor types such as lymphoma, cancer of the breast, lung, ovary and stomach. The objective of this work was to demonstrate direct radiolabeling of epirubicin with 99m Tc, quality control, biological characterization and scientigraphic evaluation in tumor bearing mice. The 99mTc-epirubicin labeling was optimized by varying the amounts of ligand 100-350μg, stannous chloride dihydride 20-50μg and pH range 2-10 by using NaOH or HCl. The radiochemical purity of 99m Tc-epirubicin was evaluated by chromatographic techniques (Whatman No. 3 paper and ITLC-SG). HPLC analyses were performed to check purity of epirubicin and radiochemical purity of labeled 99m Tc- epirubicin. Biodistribution and scintigraphic imaging of 99m Tc-epirubicin was performed in normal and tumor bearing mice at various time intervals. The optimum conditions ensuring 99m Tc-epirubicin labeling yield as high as 99% by adding 35μg SnCl 2 .2H 2 O, 200μg of ligand at pH 6 for 30 min at room temperature (25°C±2°C). HPLC of 99m Tc-epirubicin shows about 99% binding of the compound with technetium-99m. Electrophoresis study indicated the neutral nature of 99m Tc-epirubicin. Biodistribution data and scintigraphic results showed that 99m Tc-epirubicin accumulated in the liver as well as in tumor with significant uptake and excellent retention. 99m Tc-epirubicin shows good stability in human serum. In vitro and in vivo studies revealed the significantly uptake of 99m Tc-epirubicin in the tumor, and also indicating the efficiency of 99m Tc-epirubicin as a tumor diagnostic agent.

Background: Candida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated 99m Tc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection., Methods: Fluconazole was radiolabeled with technetium-99 metastable ( 99m Tc) and encapsulated into conventional ( 99m Tc-Fluconazole-PLA-POLOX) and surface-modified ( 99m Tc-Fluconazole-PLA-PEG) NCs by the interfacial deposition of the preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by solvent evaporation. The size distribution and zeta potential of the NCs preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. Free and encapsulated 99m Tc-fluconazole were administered intravenously in immunosuppressed mice bearing a local infection induced by Candida Albicans inoculation in the right thigh muscle. At pre-established time intervals, tissues and organs of interest were removed and radioactivity was measured in an automatic gamma radiation counter., Results: The NCs diameter was between 200 and 400 nm with negative zeta potential values. Free 99m Tc-fluconazole was more rapidly eliminated by the renal system compared to the encapsulated drug in NCs, which remained longer in blood circulation. The uptake of conventional NCs by mononuclear phagocyte system organs was higher than the one demonstrated by the surface-modified NCs. Both NCs remained longer in the infectious focus when compared to free 99m Tc-fluconazole, but the results did not show a significant difference between NC formulations., Conclusion: These data indicate that these NCs might represent a therapeutic alternative for the treatment of candidiasis, once they remain more time in the infectious focus, allowing high retention of 99m Tc-fluconazole at this site., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

In the synthesis of technetium-99m ( 99m Tc) labeled target-specific ligands, the presence of a large excess of unlabeled ligands over 99m Tc in the injectate hinders target accumulation of 99m Tc-labeled ligands by competing for target molecules. To circumvent the problem, we recently developed a concept of the metal coordination-mediated multivalency, and proved the concept with a 99m Tc-labeled trivalent compound [ 99m Tc(CO) 3 (CN-RGD) 3 ] + . In this study, D-penicillamine (Pen) was selected as a chelating molecule and a cyclic RGDfK peptide was conjugated to Pen via a hexanoic linkage (Pen-Ahx-c(RGDfK)). 99m Tc complexation reaction, and the stability, integrin α v β 3 binding affinity, and biodistribution of the 99m Tc-labeled probe were investigated to evaluate the applicability of the concept to bivalent probes. 99m Tc-[Pen-Ahx-c(RGDfK)] 2 was obtained over 95% radiochemical yields under low Pen-Ahx-c(RGDfK) concentration (50 μM). 99m Tc-[Pen-Ahx-c(RGDfK)] 2 showed approximately 10-times higher integrin α v β 3 binding affinity than the monovalent compounds, Pen-Ahx-c(RGDfK) and c(RGDyV). In biodistribution studies, the tumor accumulation of 99m Tc-[Pen-Ahx-c(RGDfK)] 2 was decreased to 77% and 43% of HPLC-purified (Pen-Ahx-c(RGDfK)-free) 99m Tc-[Pen-Ahx-c(RGDfK)] 2 by the presence of 5 nmol of unlabeled Pen-Ahx-c(RGDfK) and Re-[Pen-Ahx-c(RGDfK)] 2 , respectively. 99m Tc-[Pen-Ahx-c(RGDfK)] 2 provided tumor image without removing unlabeled ligand, while a 99m Tc-labeled monovalent probe prepared from a monovalent ligand could not. These findings indicate the availability of the design concept to prepare 99m Tc-labeled bivalent probes with a variety of 99m Tc core and other metallic radionuclides of clinical relevance.

Leuprolide acetate (LPA), a GnRH analogue, is drug of choice for treatment of uterine fibroids and endometriosis. The current marketed formulations of LPA show severe systemic side effects. This project aims to formulate LPA loaded liposomes to be administered by vaginal route for uterine targeting. Liposomes were prepared by thin film hydration method using 1:1 M ratio of DSPC: Cholesterol and characterized for vesicle size, zeta potential, entrapment efficiency, and loading. Radiolabeling of LPA was performed by direct labeling with reduced technetium-99m. Binding affinity of 99mTc-labeled complexes was assessed by diethylenetriaminepentaacetic acid (DTPA) challenge test. Biodistribution study was done in New Zealand white female rabbits by administering the formulation via vaginal route. Spherical and discrete vesicles of size 189 nm were seen in TEM results with entrapment efficiency and loading of 74.36% and 9.29%w/w, respectively. Liposomes were able to sustain the drug release for 5 days. 99mTc-labeled complexes showed high labeling efficiency and stability both in saline and serum. DTPA challenge test confirmed low transchelation of 99mTc-labeled complexes. Biodistribution study by gamma scintigraphy revealed the preferential uptake of the formulation by uterus when administered vaginally. Compared to plain drug, liposomes concentrated and were retained within the uterus for a longer period of time. Uterine targeting of liposomal LPA indicates its potential to overcome the limitations of presently available formulations. Hence, this seems to be a promising approach for targeting the drugs, whose site of action is uterus.