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

In this study, we compared in vitro and in vivo results of the 99mTc-labeled HYNIC-KRWrNM in the presence of Tricine/EDDA and Tricine/Nicotinic acid (NA) as two co-ligand systems ([99mTc]Tc-M-7 and [99mTc]Tc-M-6, respectively). The dissociation constant (Kd) value of [99mTc]Tc-M-6 was 7.1 ± 2.3 nM for U87-MG cell line (glioblastoma). Based on biodistribution studies, the tumor-to-muscle ratio of [99mTc]Tc-M-6 was 8.77 and 11.33 at 1.5 and 4 h after injection, respectively. Finally, target-to-background ratio in the planar gamma image was 12.03 at 4 h after injection. By comparison, our experimental results showed that substitution of EDDA by Nicotinic acid in the 99mTc-labeling of HYNIC-KRWrNM led to the formation of an improved tumor-targeting peptide. This improved radio-peptide can be a potential agent for the diagnosis of integrin αvβ3-positive tumors. [ABSTRACT FROM AUTHOR]

Background: Personalised multi-compartment dosimetry based on [99mTc]Tc-MAA is a valuable tool for planning 90Y radioembolization treatments. The establishment and effective application of dose–effect relationships in yttrium-90 (90Y) radioembolization requires [99mTc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [99mTc]Tc-MAA imaging and evaluate a standardised imaging protocol. Data was obtained from the TARGET study, an international, retrospective multi-centre study including 14 sites across 8 countries. The impact of imaging related factors was estimated using a NEMA IQ phantom (representing the liver), and a uniformly filled cylindrical phantom (representing the lungs). Imaging was performed using site-specific protocols and a standardized protocol. In addition, the impact of implementing key image corrections (scatter and attenuation correction) in the site-specific protocols was investigated. Inter-site dosimetry accuracy was evaluated by comparing computed Lung Shunt Fraction (LSF) measured using planar imaging of the cylindrical and NEMA phantom, and contrast recovery coefficient (CRC) measured using SPECT imaging of the NEMA IQ phantom. Results: Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6–10.1%). A standardised protocol did not improve variation (interquartile range 8.4–9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5–0.7 and 0.6–0.8 respectively), however the standardised protocol did improve accuracy of sphere:background determination. Implementation of key image corrections did improve inter-site variation (CRC interquartile range for 37 mm sphere 0.6–0.7). Conclusion: Eliminating sources of variability in image corrections between imaging protocols reduces inter-site variation in quantification. A standardised protocol was not able to improve consistency of LSF or CRC but was able to improve accuracy. [ABSTRACT FROM AUTHOR]

Using a one-pot cyclo-condensation process under microwave irradiation, derivatives of curcumin have been created. Evaluation their anti-inflammatory efficacy showed that they had stronger properties than curcumin. Additionally, the most active derivative was radiolabeled with the diagnostic radioisotope technetium-99m and prepared with a high radiochemical yield (96.5 ± 0.09%) and in vitro stability of up to 6 h. The in-vivo study in inflamed mice showed that [99mTc]Tc-curcumin derivative accumulated with a high target to non-target ratio. The gathered information confirmed the efficacy of the [99mTc]Tc-curcumin derivative as a novel possible tracer for the identification and localization of inflammation. [ABSTRACT FROM AUTHOR]

Synaptic trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) is thought to cause excitotoxicity brain ischemia. However, given the current inability to quantify AMPARs density in live human brains, clinical translation has been limited. In this study, in vivo and in vitro experiments were conducted to evaluate the factors affecting omberacetam drug labeling with technetium-99m as a potential radiotracer of AMPARs in brain imaging. Healthy Swiss albino mice (adult male; n = 25; weight 25–30 g; age 10–14 weeks) underwent Shimadzu modeling, followed by a random intravenous injection of 99mTc-omberacetam (0.2 mL, 3.7 MBq), which was subsequently radiosynthesized in the brain-targeting AMPARs utilizing a single-photon emission computed tomography nuclear neuroimaging. Under optimal conditions, 99mTc-omberacetam with a highest radiochemical purity of 98.9% was obtained with an optimum binding (energy = − 82.3 kcal/mol) to brain AMPARs and was stable in human serum for > 24 h. A high brain uptake was noted within a time window of 15–60 min. At 5 min, this signal uptake was 8.9 ± 0.1% of the injected dose per gram (ID/g), crossing the blood–brain barrier and surpassing the uptake of commercially available brain perfusion imaging agents such as 125I-iododomperidone (5.6% ID/g at 5 min) in mice, 99mTc-HMPAO (2.25% ID/g at 2 min) in rats, and 99mTc-ECD (4.7% ID/g at 6 h) in humans. This study is the first to show the feasibility of 99mTc-omberacetam radiotracing for human brain imaging. This could be a novel diagnostic and therapeutic neuroprotective target for the hyperacute stage of ischemic stroke. [ABSTRACT FROM AUTHOR]

Metallothioneins are a special group of low-molecular-weight proteins with metal-binding properties, which make them promising chelators for the development of targeted radiopharmaceuticals, as well as with technetium-99m. The aim of this work is to study the biodistribution of 99mTc-metallothionein conjugate (99mTc-MT) in intact mice in comparison with unbound technetium-99m (Na99mTcO4). Low uptake of 99mTc-MT in the thyroid gland (1.20 ± 0.30%/g versus 267.2 ± 59.0%/g for Na99mTcO4) demonstrates the high stability of 99mTc-MT in vivo. The 99mTc-MT complex is rapidly eliminated from the bloodstream through the kidneys and is characterized by a reduced uptake in most organs and tissues compared to Na99mTcO4. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA), which is overexpressed in advanced prostate cancer, is a well-established target for the development of antitumor diagnostic and therapeutic radiopharmaceuticals. The aim of this work is the preclinical study of the pharmacokinetics of a new radiopharmaceutical 99mTc-PSMA. Tumor uptake of 99mTc-PSMA is 1.81–3.91%/g with a maximum uptake of 3.91 ± 0.35%/g at 3 h of post-injection. The highest uptake (up to 140.11%/g) of 99mTc-PSMA throughout the study was observed in the kidneys. Tumor uptake of 99mTc-PSMA was higher than in other organs and tissues, except the kidneys [ABSTRACT FROM AUTHOR]

Background: Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O-TRENSOX and O-TRENOX two synthetic siderophores would be good candidates for this purpose as they are hexadentate ligands based on the very versatile and efficient 8-hydroxyquinoline chelating subunit. First, the radiolabeling of O-TRENOX and O-TRENSOX with 99mTc was investigated. Different parameters such as the quantity of chelating agent, type of reducing agent, pH and temperature of the reaction mixture were adjusted in order to find the best radiolabeling conditions. Then an assessment of the partition coefficient by measuring the distribution of each radiosynthesized complex between octanol and phosphate-buffered saline was realized. The complex's charge was evaluated on three different celluloses (neutral, negatively charged P81 and positively charged DE81), and finally in vivo studies with biodistribution and SPECT imaging of [99mTc]Tc-O-TRENOX and [99mTc]Tc-O-TRENSOX were performed. Results: The radiolabeling studies showed a rapid and efficient complexation of 99mTc with both chelating agents. Using tin pyrophosphate as the reducing agent and a minimum of 100 nmol of ligand, we obtained the [99mTc]Tc-O-TRENOX complex with a radiochemical purity of more than 98% and the [99mTc]Tc-O-TRENSOX complex with one above 97% at room temperature within 5 min. [99mTc]Tc-O-TRENOX complex was lipophilic and neutral, leading to a hepatobiliary elimination in mice. On the contrary, the [99mTc]Tc-O-TRENSOX complex was found to be hydrophilic and negatively charged. This was confirmed by a predominantly renal elimination in mice. Conclusions: These encouraging results allow us to consider the O-TRENOX/99mTc and O-TRENSOX/99mTc complexes as serious candidates for SPECT imaging chelators. This study should be continued by conjugating these tris-oxine ligands to peptides or antibodies and comparing them with the other bifunctional agents used with Tc. [ABSTRACT FROM AUTHOR]

[99mTc] fonturacetam hydrazide was radiosynthesized to assess neuropsychiatric disorders by targeting the brain. The nootropic drug was labeled with technetium-99m, and factors affecting the labeling yield were studied. At optimum conditions, the radiocomplex was obtained at a high radiochemical yield (98.9%) and was stable in saline for up to 36 h and serum for more than 24 h. Labeled fonturacetam hydrazide was characterized and assessed in silico. Biodistribution studies in mice showed that the brain uptake of the complex was 8.8% injected dose per gram (% ID/g) at 5 min post-injection, surpassing the commercially available [99mTc] ECD (4.7% ID/g) and [99mTc] HMPAO (2.25% ID/g). All results suggested that the tracer is a good candidate to image the human brain for assessing neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

The current research was performed to assess the localization of radiolabeled Carnitine (CARNT) in different organs of rats. Radiolabeling of Carnitine (CARNT) was performed using Tc-99m with reasonable purity of 96.7±2.21% at the optimum conditions. The radiochemical purification of the 99mTc-CARNT was achieved by the TLC tool in two solvents and confirmed by the electrophoresis procedure. The 99mTc-CARNT was injected into three groups of rats. These rats were classified into three groups: the first one is a control group, the second was a pretreated group which was the toxicity group primarily treated by inactive Carnitine, and the last group is the toxicity rats group. The toxicity of rats was induced by Trichloroacetic Acid (TCA). The biochemical markers were done to describe the impacts of TCA on the enzymes and lipids of the rats. The accumulation of 99mTc-CARNT was examined at various times from 15.00 min to 120.00 min in three groups of rats (control, pretreated, and toxicity rats). The results explained that the 99mTc-CARNT was accumulated in the hepatotoxicity liver which was induced by the TCA higher than in control and pretreated rats. Hence, the data exhibited that the 99mTc-CARNT may be helpful for the determination of hepatocyte dysfunction in rats. [ABSTRACT FROM AUTHOR]

Avanafil was labeled with technetium-99m for diagnostic evaluation of erectile dysfunction. The labeling conditions were optimized to reach a high radiolabeling yield (98.6%). The complex showed good stability for up to 24 h in saline and 20 h in serum. The structure of the labeled complex was confirmed. Molecular modeling and docking to the PDE5 enzyme were performed to evaluate the complex fitting and binding to its biochemical target. Biodistribution in normal rats and three different models of erectile dysfunction were performed. The results strongly suggest that 99mTc-avanafil is a promising tracer for erectile dysfunction in humans. [ABSTRACT FROM AUTHOR]

Background: Radioguided surgery (RGS) has recently emerged as a valuable new tool in the management of recurrent prostate cancer (PCa). After preoperative injection of a 99mTc-labeled prostate-specific membrane antigen (PSMA) inhibitor, radioguided intraoperative identification and resection of lesions is facilitated by means of suitable γ-probes. First clinical experiences show the feasibility of RGS and suggest superiority over conventional lymph node dissection in recurrent PCa. However, commonly used [99mTc]Tc-PSMA-I&S exhibits slow whole-body clearance, thus hampering optimal tumor-to-background ratios (TBR) during surgery. We therefore aimed to develop novel 99mTc-labeled, PSMA-targeted radioligands with optimized pharmacokinetic profile to increase TBR at the time of surgery. Methods: Three 99mTc-labeled N4-PSMA ligands were preclinically evaluated and compared to [99mTc]Tc-PSMA-I&S. PSMA affinity (IC50) and internalization were determined on LNCaP cells. Lipophilicity was assessed by means of the distribution coefficient logD7.4 and an ultrafiltration method was used to determine binding to human plasma proteins. Biodistribution studies and static µSPECT/CT-imaging were performed at 6 h p.i. on LNCaP tumor-bearing CB17-SCID mice. Results: The novel N4-PSMA tracers were readily labeled with [99mTc]TcO4− with RCP > 95%. Comparable and high PSMA affinity was observed for all [99mTc]Tc-N4-PSMA-ligands. The ligands showed variable binding to human plasma and medium to low lipophilicity (logD7.4 − 2.6 to − 3.4), both consistently decreased compared to [99mTc]Tc-PSMA-I&S. Biodistribution studies revealed comparable tumor uptake among all [99mTc]Tc-N4-PSMA-ligands and [99mTc]Tc-PSMA-I&S, while clearance from most organs was superior for the novel tracers. Accordingly, increased TBR were achieved. [99mTc]Tc-N4-PSMA-12 showed higher TBR than [99mTc]Tc-PSMA-I&S for blood and all evaluated tissue. In addition, a procedure suitable for routine clinical production of [99mTc]Tc-N4-PSMA-12 was established. Labeling with 553 ± 187 MBq was achieved with RCP of 98.5 ± 0.6% (n = 10). Conclusion: High tumor accumulation and favorable clearance from blood and non-target tissue make [99mTc]Tc-N4-PSMA-12 an attractive tracer for RGS, possibly superior to currently established [99mTc]Tc-PSMA-I&S. Its GMP-production according to a method presented here and first clinical investigations with this novel radioligand is highly recommended. [ABSTRACT FROM AUTHOR]

Carum carvi-derived quantum dots (CcQDs) were prepared using thermal pyrolyzing. The surface functionalization of CcQDs were achieved via L-cysteine ligand. Labeled CcQDs with technetium-99m were prepared using a simple direct radiolabeling method. Radio chromatographic techniques were used to analyze radiochemical yield. Quality control results indicated that QDs could be efficiently labeled with 99mTc-radionuclide (> 98% radiochemical yield). The in vivo biodistribution parameters were studied in tumorized BALB/c mouse. The amount of uptake in xenograft models of mice colon carcinoma was 1.27 ± 0.15% ID/g after 1 h. 99mTc-labeled T-Cysteine-CcQDs, could be included as a radiotracer for imaging colon carcinoma tumors. [ABSTRACT FROM AUTHOR]

This study aimed to synthesize a new pyrimidine derivative with a good synthesis yield of 87% to act as a new cancer marker after radiolabeling with Tc-99m in a high radiochemical yield of 92.3%. In-vivo study in tumor-bearing Swiss albino mice model revealed promising data with high uptake in cancer. Docking study showed good binding interactions of the radiosynthesized complex at the binding site. In conclusion, this novel complex could be a potential probe for cancer targeting. [ABSTRACT FROM AUTHOR]

In the present work the synthesis, physicochemical properties and biological evaluation of cefepime (CFM) labelled with technetium-99m were studied. Two different synthesis routes of DTPA-CFM as well as the radiolabelling conditions were described. Radiochemical purity of the radioconjugates determined using radio-TLC and HPLC methods with radiochemical detection was higher than 95%. The obtained [99mTc]Tc-DTPA-CFM radioconjugate is highly hydrophilic (logD = − 4.00 ± 0.14) and positively charged. It is completely stable in the presence of an excess of cysteine or histidine, acceptably stable in human serum and shows satisfactorily binding to the Staphylococcus aureus cell wall. Based on our results the [99mTc]Tc-DTPA-CFM radioconjugate may be considered to be a diagnostic radiopharmaceutical for detection of staphylococcal infections. [ABSTRACT FROM AUTHOR]

Background: Anthropomorphic torso phantoms, including a cardiac insert, are frequently used to investigate the imaging performance of SPECT and PET systems. These phantom solutions are generally featuring a simple anatomical representation of the heart. 3D printing technology paves the way to create cardiac phantoms with more complex volume definition. This study aimed to describe how a fillable left ventricular myocardium (LVm) phantom can be manufactured using geometry extracted from a patient image. Methods: The LVm of a healthy subject was segmented from 18F-FDG attenuation corrected PET image set. Two types of phantoms were created and 3D printed using polyethylene terephthalate glycol (PETG) material: one representing the original healthy LVm, and the other mimicking myocardium with a perfusion defect. The accuracy of the LVm phantom production was investigated by high-resolution CT scanning of 3 identical replicas. 99mTc SPECT acquisitions using local cardiac protocol were performed, without additional scattering media ("in air" measurements) for both phantom types. Furthermore, the healthy LVm phantom was inserted in the commercially available DataSpectrum Anthropomorphic Torso Phantom ("in torso" measurement) and measured with hot background and hot liver insert. Results: Phantoms were easy to fill without any air-bubbles or leakage, were found to be reproducible and fully compatible with the torso phantom. Seventeen segments polar map analysis of the "in air" measurements revealed that a significant deficit in the distribution appeared where it was expected. 59% of polar map segments had less than 5% deviation for the "in torso" and "in air" measurement comparison. Excluding the deficit area, neither comparison had more than a 12.4% deviation. All the three polar maps showed similar apex and apical region values for all configurations. Conclusions: Fillable anthropomorphic 3D printed phantom of LVm can be produced with high precision and reproducibility. The 3D printed LVm phantoms were found to be suitable for SPECT image quality tests during different imaging scenarios. The flexibility of the 3D printing process presented in this study provides scalable and anthropomorphic image quality phantoms in nuclear cardiology imaging. [ABSTRACT FROM AUTHOR]

Background: Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. Nanomedicine, a term for the application of nanotechnology in medical and health fields, uses nanoparticles for several applications such as imaging, diagnostic, targeted cancer therapy, drug and gene delivery, tissue engineering, and theranostics. Results: Here, we overview the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and radionuclide therapy. Nanostructured radiopharmaceuticals of technetium-99m, copper-64, lutetium-177, and radium-223 are discussed within the scope of this review article. Conclusion: Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment. [ABSTRACT FROM AUTHOR]

Antineoplastons (ANPs) are compounds that have antitumor activities. ANPA10 was labeled with technetium-99m using stannous chloride as a reducing agent with the labeling yield of approximately 98% at pH 6. The conditions required to optimize the labeling yield were studied in details. The tumor binding specificity of the [99mTc]Tc-ANPA10 radiotracer was evaluated. The uptake of [99mTc]Tc-ANPA10 in ascitic fluid uptake was 10, 16, and 12.8% ID/g at 30, 60, and 120 min post injection. The preclinical biological evaluation of [99mTc]Tc-ANPA10 complex in solid tumor bearing mice showed a high tumor uptake at 1 h post injection (11.2 ± 0.30 % ID/g). The selective uptake of [99mTc]Tc-ANPA10 in solid tumors and rapid clearance from nontarget organs make it promising for solid tumor imaging, but further clinical trials are required. [ABSTRACT FROM AUTHOR]

This study aimed to develop a single photo emission computed tomography/fluorescence (SPECT/FL) bimodal imaging probe to image blood cells. Hyperbranched polyglycerol (HPG) was synthesized by anionic ring-opening polymerization. Succinic anhydride was used to functionalize HPG. Then, indocyanine green (ICG) was bound to HPG, with a 73.59% binding yield. Deferoxamine (DFO) was subsequently bound to ICG-HPG, and DFO-ICG-HPG was radiolabeled with technetium-99m, with 100% yield. The molecular weight of HPG in this study was found to be 6.8 kDa. In in vitro studies, the radiolabeled nanoconjugates remained stable even after 6 h (last timepoint when stability was assessed), and when the nanoconjugates were applied to K562 chronic myeloid leukemia cells, the highest cell viability was observed at a concentration of 5 µg/mL and binding efficiency increased over time, reaching 30% at 6 h (last timepoint when binding efficiency was assessed). The results support the feasibility of the developed probe to image blood cells, which would be useful for applications such as detecting internal bleeding. [ABSTRACT FROM AUTHOR]

About 35% reduction in cancer deaths among patients having solid tumors is related to using aspirin, which encouraged us to develop a new specific tumor diagnostic radiopharmaceutical agent. This can be done by direct labeling of aspirin with technetium-99m using stannous chloride as a reductant at pH 9. At this pH, aspirin is saponificated to salicylate ions. Salicylate binds to pertechenetate to form 99mTc salicylate complex. The radiochemical yield (RCY, %) of 99mTc-salicylate complex obtained from aspirin was determined using paper chromatography, electrophoresis, and HPLC and was found to reach 90.2%. The 99mTc salicylate complex obtained from aspirin was stable for up to 5 h. The tumor uptake of the 99mTc salicylate complex obtained from aspirin was determined by ex-vivo study in tumor-bearing mice. This study showed that 99mTc salicylate complex was concentrated in tumor sites (ascites or solid), allowing tumor radioimaging. High target/non-target (tumor muscles/normal muscles) uptake ratio shows that 99mTc salicylate complex can be utilized for early detection of solid tumors. Molecular modeling and docking study conofirm the possibility of using the radiolabeled 99mTc salicylate complex for specific cancer imaging in binding with epidermal growth factor receptors (EGFR). [ABSTRACT FROM AUTHOR]

2,3,7,8,12,13,17,18-Octaethyl-21H,23H-porphine (OEP) was successfully radiolabeled with technetium-99m by direct technique using two different reducing agents: stannous chloride and sodium borohydride. High radiochemical yield (97%) and in vitro stability for up to 8 h were obtained using sodium borohydride. Paper chromatography (PC), paper electrophoresis, and high-performance liquid chromatography (HPLC) were used to evaluate the radiochemical yield and identify the purity of the final product. Biodistribution studies of the 99mTc-OEP complex (prepared using sodium borohydride) in tumor-bearing mice showed high target/nontarget (T, right thigh/NT, left thigh) ratio of 4.40 ± 0.12 at 60 min post injection, suggesting that this complex can be used as a solid tumor imaging agent. [ABSTRACT FROM AUTHOR]

The results of studies performed at the Khlopin Radium Institute in cooperation with other institutions from Russia and other countries, and also published data in the field of chemistry of higher technetium carbonyl compounds are summarized in the context of problems of nuclear medicine. Chemical problems that arise on the way of using higher technetium carbonyls in nuclear medicine and are associated with the synthesis conditions and reactivity of these complexes, and also the ways to solve these problems are analyzed. The major problems are the need for using high pressures in synthesis, the impossibility of direct replacement of halogen in pentacarbonyl halides (products directly obtained from pertechnetate ion) by other monodentate ligands, limited resistance of many higher technetium carbonyls to decarbonylation, and susceptibility of higher technetium carbonyls to nucleophilic reactions (including hydrolysis in alkaline media). The latter problem seems to be the most critical. The scientific outcome of the studies is outlined, and comparison with rhenium analogs is made. The complex [99mTcI(CO)5] shows promise for lung imaging; assumptions concerning the mechanism of its lung uptake are formulated. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this work was to develop hydrophilic gastrin-releasing peptide receptor (GRPR)-targeting complexes of the general formula fac-[M(CO)3(L)]+ [M = natRe, 99mTc, 186Re; L: NOTA for 1, NODAGA for 2] conjugated to a powerful GRPR peptide antagonist (DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) via a 6-aminohexanoic acid linker. Procedures: Metallated-peptides were prepared employing the [M(OH2)3(CO)3]+ [M = Re, 99mTc, 186Re] precursors. Re-1/2 complexes were characterized with HR-MS. IC50 studies were performed for peptides 1/2 and their respective Re-1/2 complexes in a binding assay utilizing GRPR-expressing human PC-3 prostate cancer cells and [125I]I-Tyr4-BBN as the competing ligand. The 99mTc/186Re-complexes were identified by HPLC co-injection with their Re-analogues. All tracers were challenged in vitro at 37 °C against cysteine/histidine (phosphate-buffered saline 10 mM, pH 7.4) and rat serum. Biodistribution and micro-SPECT/CT imaging of [99mTc]Tc-1/2 and [186Re]Re-2 were performed in PC-3 tumor-bearing ICR SCID mice. Results: High in vitro receptor affinity (IC50 2–3 nM) was demonstrated for all compounds. The 99mTc/186Re-tracers were found to be hydrophilic (log D7.4 ≤ − 1.35) and highly stable. Biodistribution in PC-3 xenografted mice revealed good tumor uptake (%ID/g at 1 h: 4.3 ± 0.7 for [99mTc]Tc-1, 8.3 ± 0.9 for [99mTc]Tc-2 and 4.2 ± 0.8 for [186Re]Re-2) with moderate retention over 24 h. Rapid renal clearance was observed for [99mTc]Tc-2 and [186Re]Re-2 (> 84 % at 4 h), indicating favorable pharmacokinetics. Micro-SPECT/CT images for the 99mTc-tracers clearly visualized PC-3 tumors in agreement with the biodistribution data and with superior imaging properties found for [99mTc]Tc-2. Conclusions: [99mTc]Tc-2 shows promise for further development as a GRPR-imaging agent. [186Re]Re-2 demonstrated very similar in vivo behavior to [99mTc]Tc-2, and further studies are therefore justified to explore the theranostic potential of our approach for targeting of GRPR-positive cancers. [ABSTRACT FROM AUTHOR]

We studied an original radiolabeled complex of antimicrobial peptides UBI29-41 and UBI18-35, ubiquicidin derivatives, for distinguishing between bacterial and aseptic inflammation. For radiolabeling of the peptides with technetium-99m, a bifunctional chelating agent succinimide-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used. The obtained complexes 99mТс-DPAH-UBI29-41 and 99mТс-DPAH-UBI18-35 had radiolabeling yield >80% and radiochemical purity >96%. Accumulation of the complexes in the focus of bacterial inflammation in bone structures and the absence of this complex in the site of aseptic inflammation was confirmed in a rat model of traumatic osteomyelitis by single-photon emission computed tomography. [ABSTRACT FROM AUTHOR]

Thidiazuron (TDZ) was reported to possess anti-cancer activity against Human cervical carcinoma cell line, so that this study has been conducted for the radiolabeling of TDZ with Technetium-99m. The conditions of the radiolabeling process were optimized and a high radiochemical yield of 93.1 ± 0.35% has been obtained. Molecular docking study illustrated that [99mTc]technetium bisthiadiazuron (99mTc-TDZ) complex has the ability to bind with Caspase-3 protein that over expressed in cancers. Its in-vivo biodistribution on solid tumor bearing mice showed comparatively high T/NT ratio of 6.87 ± 0.14 at 60 min post injection. These promising characteristics make our new designed labeled conjugate a very suitable candidate for molecular imaging of solid tumors, particularly in the cervix. [ABSTRACT FROM AUTHOR]

A novel sulphonamide derivative (EPBS) was prepared at high yield and characterized by 1H NMR and infrared radiation spectroscopy. Its cytotoxic activity was examined in breast carcinoma (MCF-7) cells at a dose of 25 μg/mL. Approximately 68 percent effective inhibition has been achieved. Furthermore, the synthesized ligand was directly radiolabeled with technetium-99m using sodium borohydride. High radiochemical purities (95.5%) were determined using radio-paper chromatography and electrophoresis. Its in vivo evaluation in tumor bearing mice demonstrated a high tumor uptake of the 99mTc-EPBS complex at 30 min post injection (6.74%) and tumor/muscle (T/NT) ratio equal to 5.04 ± 0.05. In conclusion, 99mTc-EPBS agent showed favorable characteristics for the radio-diagnosis of solid tumors. [ABSTRACT FROM AUTHOR]

Background: Recently, a new family of 99mTc(I)-tricarbonyl complexes bearing an acridine orange (AO) DNA targeting unit and different linkers between the Auger emitter (99mTc) and the AO moiety was evaluated for Auger therapy. Among them, 99mTc-C3 places the corresponding radionuclide at a shortest distance to DNA and produces important double strand breaks (DSB) yields in plasmid DNA providing the first evidence that 99mTc can efficiently induce DNA damage when well positioned to the double helix. Here in, we have extended the studies to human prostate cancer PC3 cells using the 99mTc-C3 and 99mTc-C5 complexes, aiming to assess how the distance to DNA influences the radiation-induced biological effects in this tumoral cell line, namely, in which concerns early and late damage effects. Results: Our results highlight the limited biological effectiveness of Auger electrons, as short path length radiation, with increasing distances to DNA. The evaluation of the radiation-induced biological effects was complemented with a comparative microdosimetric study based on intracellular dose values. The comparative study, between MIRD and Monte Carlo (MC) methods used to assess the cellular doses, revealed that efforts should be made in order to standardize the bioeffects modeling for DNA-incorporated Auger electron emitters. Conclusions: 99mTc might not be the ideal radionuclide for Auger therapy but can be useful to validate the design of new classes of Auger-electron emitting radioconjugates. In this context, our results highlight the crucial importance of the distance of Auger electron emitters to the target DNA and encourage the development of strategies for the fine tuning of the distance to DNA for other medical radionuclides (e.g., 111In or 161Tb) in order to enhance their radiotherapeutic effects within the Auger therapy of cancer. [ABSTRACT FROM AUTHOR]

Nanodiamonds (NDs) were investigated as potential carriers of 99mTc, which is widely used for the diagnosis of diseases in nuclear medicine. The sorption of 99Tc(VII), 99mTc(VII), and 99mTc(IV) by commercial NDs and their reduced, aminated, and oxidized forms was studied. The physicochemical parameters of the Langmuir and Freundlich isotherms for the sorption of 99Tc(VII) by the used ND samples were determined. The Sn(II): Tc(VII) ratio for the quantitative reduction of Tc to the oxidation state IV was optimized. It was shown that the initial (commercial) and oxidized NDs are promising carriers of 99mTc(IV) for nuclear medicine. [ABSTRACT FROM AUTHOR]

Amount estimation of production of 99Mo required for medical applications was carried out by utilizing an electron linear accelerator with 30 g of natMoO3 target, and 15.10 MBq of 99Mo was obtained after 9.5 min of irradiation with bremsstrahlung photons by a 35 MeV-80 μA electron beam. Requirements for further scaled-up production with 100MoO3 target (100 g, φ20 mm × t30 mm) were analyzed using Monte Carlo simulation. It was found that it had to be irradiated with 20 h of bremsstrahlung photons by a 35 MeV-1 mA electron beam to produce 1340 GBq of 99Mo. [ABSTRACT FROM AUTHOR]

Background: For multicenter clinical studies, PET/CT and SPECT/CT scanners need to be validated to ensure comparability between various scanner types and brands. This validation is usually performed using hollow phantoms filled with radioactive liquids. In recent years, 3D printing technology has gained increasing popularity for manufacturing of phantoms, as it is cost-efficient and allows preparation of phantoms of almost any shape. So far, however, direct 3D printing with radioactive building materials has not yet been reported. The aim of this work was to develop a procedure for preparation of 99mTc-containing building materials and demonstrate successful application of this material for 3D printing of several test objects. Method: The desired activity of a [99mTc]pertechnetate solution eluted from a 99Mo/99mTc-generator was added to the liquid 3D building material, followed by a minute amount of trioctylphosphine. The resulting two-phase mixture was thoroughly mixed. Following separation of the phases and chemical removal of traces of water, the radioactive building material was diluted with the required volume of non-radioactive building material and directly used for 3D printing. Results: Using our optimized extraction protocol with trioctylphosphine as complex-forming phase transfer agent, technetium-99m was efficiently transferred from the aqueous 99Mo/99mTc-generator eluate into the organic liquid resin monomer. The observed radioactivity concentration ratio between the organic phase and the water phase was > 2000:1. The radioactivity was homogeneously distributed in the liquid resin monomer. We did not note differences in the 3D printing behavior of the radiolabeled and the unlabeled organic liquid resin monomers. Radio-TLC and SPECT studies showed homogenous 2D and 3D distribution of radioactivity throughout the printed phantoms. The radioactivity was stably bound in the resin, apart from a small amount of surface-extractable radioactivity under harsh conditions (ethanol at 50 °C). Conclusions: 3D printing of radioactive phantoms using 99mTc-containing building materials is feasible. Compared to the classical fillable phantoms, 3D printing with radioactive building materials allows manufacturing of phantoms without cold walls and in almost any shape. Related procedures with longer-lived radionuclides will enable production of phantoms for scanner validation and quality control. [ABSTRACT FROM AUTHOR]

Molybdenum-99 (99Mo), in the form of 99Mo-alfa-benzoin oxime (99Mo-ABO) complex was developed as industrial radiotracer and its performance was tested in a diesel hydro-treater unit of a leading oil refinery. Main objective of the study was to evaluate the suitability of the developed 99Mo-ABO complex for industrial applications at high temperature and high-pressure hydrocarbon stream. A methodology was developed to convert the aqueous solution of fission 99Mo into 99Mo-ABO complex, suitable for mixing with organic phase. A radiotracer study was carried out to identify the leaky heat exchangers from a series of four heat exchangers using 99Mo-ABO complex in organic phase as a novel industrial radiotracer. Reproducibility of the result was verified by using 99mTc in organic phase as another radiotracer. From the study it was found that the developed radiotracer '99Mo-ABO complex' is suitable for industrial applications at high temperature and high-pressure hydrocarbon streams. [ABSTRACT FROM AUTHOR]

Preclinical studies of a new octreotide derivative with a chelate (DPAH-octreotide) that binds 99mTc for radiological diagnosis of neuroendocrine tumors are currently in progress. A method for preparing DPAH-octreotide is based on forming an amide bond between the amine of D-phenylalanine and the bifunctional chelate succinimid-1-yl 6-[bis(pyridin-2-ylmethyl)amino]hexanoate. An HPLC method for determining the identity, impurities, and quantitative content is proposed for DPAH-octreotide quality assurance. The validation protocol established that the HPLC analytical method for determining DPAH-octreotide had quality parameters for specificity, detection limit, linearity, accuracy, precision, and intralaboratory precision that met requirements for analytical methods and could be used for quality control of the finished product during manufacturing of reagents for preparation of related radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: In this study, a combination of nanotechnology, organic synthesis and radiochemistry were utilized in order to design an efficient nano-system conjugated with a suitable radionuclide and an antitumor agent for possible application as tumor theragnostic agent.Four novel compounds (3 and 4a-c) bearing tetrahydroquinazoline-7-sulfonohydrazide or 1,2,3,4-tetrahydroquinazoline-7-sulfonamide scaffold were designed. Then, docking study predicted that the compounds can be considered as potential inhibitors for PARP-1. Following that; the four compounds were synthesized and properly characterized using 1HNMR, 13CNMR, IR and Mass spectroscopy. The cytotoxic effect of the four compounds was evaluated against breast cancer cell line (MDA-MB-436), where compound 3 showed the most promising cytotoxic effect. The inhibitory effect of the four compounds was evaluated in vitro against PARP-1.Carboxylated graphene oxide nanosheets (NGO-COOH) were synthesized by a modified Hummer's method and has size of range 40 nm. The NGO-COOH nanosheets were proven to be safe and biocompatible when tested in vitro against normal human lung fibroblast cells (MRC-5). The prepared NGO-COOH nanosheets were conjugated with compound 3 then radiolabeled with 99mTc to yield 99mTc-NGO-COOH-3 with a radiochemical yield of 98.5.0 ± 0.5%. 99mTc-NGO-COOH-3 was injected intravenously in solid tumor bearing mice to study the degree of localization of the nano-system at tumor tissue. The results of the study revealed, excellent localization and retention of the designed nano-system at tumor tissues with targeting ratio of 9.0.Stirred a new candidate tumor theragnostic agent that is safe, selective and stable.Method: In this study, a combination of nanotechnology, organic synthesis and radiochemistry were utilized in order to design an efficient nano-system conjugated with a suitable radionuclide and an antitumor agent for possible application as tumor theragnostic agent.Four novel compounds (3 and 4a-c) bearing tetrahydroquinazoline-7-sulfonohydrazide or 1,2,3,4-tetrahydroquinazoline-7-sulfonamide scaffold were designed. Then, docking study predicted that the compounds can be considered as potential inhibitors for PARP-1. Following that; the four compounds were synthesized and properly characterized using 1HNMR, 13CNMR, IR and Mass spectroscopy. The cytotoxic effect of the four compounds was evaluated against breast cancer cell line (MDA-MB-436), where compound 3 showed the most promising cytotoxic effect. The inhibitory effect of the four compounds was evaluated in vitro against PARP-1.Carboxylated graphene oxide nanosheets (NGO-COOH) were synthesized by a modified Hummer's method and has size of range 40 nm. The NGO-COOH nanosheets were proven to be safe and biocompatible when tested in vitro against normal human lung fibroblast cells (MRC-5). The prepared NGO-COOH nanosheets were conjugated with compound 3 then radiolabeled with 99mTc to yield 99mTc-NGO-COOH-3 with a radiochemical yield of 98.5.0 ± 0.5%. 99mTc-NGO-COOH-3 was injected intravenously in solid tumor bearing mice to study the degree of localization of the nano-system at tumor tissue. The results of the study revealed, excellent localization and retention of the designed nano-system at tumor tissues with targeting ratio of 9.0.Stirred a new candidate tumor theragnostic agent that is safe, selective and stable.Result: In this study, a combination of nanotechnology, organic synthesis and radiochemistry were utilized in order to design an efficient nano-system conjugated with a suitable radionuclide and an antitumor agent for possible application as tumor theragnostic agent.Four novel compounds (3 and 4a-c) bearing tetrahydroquinazoline-7-sulfonohydrazide or 1,2,3,4-tetrahydroquinazoline-7-sulfonamide scaffold were designed. Then, docking study predicted that the compounds can be considered as potential inhibitors for PARP-1. Following that; the four compounds were synthesized and properly characterized using 1HNMR, 13CNMR, IR and Mass spectroscopy. The cytotoxic effect of the four compounds was evaluated against breast cancer cell line (MDA-MB-436), where compound 3 showed the most promising cytotoxic effect. The inhibitory effect of the four compounds was evaluated in vitro against PARP-1.Carboxylated graphene oxide nanosheets (NGO-COOH) were synthesized by a modified Hummer's method and has size of range 40 nm. The NGO-COOH nanosheets were proven to be safe and biocompatible when tested in vitro against normal human lung fibroblast cells (MRC-5). The prepared NGO-COOH nanosheets were conjugated with compound 3 then radiolabeled with 99mTc to yield 99mTc-NGO-COOH-3 with a radiochemical yield of 98.5.0 ± 0.5%. 99mTc-NGO-COOH-3 was injected intravenously in solid tumor bearing mice to study the degree of localization of the nano-system at tumor tissue. The results of the study revealed, excellent localization and retention of the designed nano-system at tumor tissues with targeting ratio of 9.0.Stirred a new candidate tumor theragnostic agent that is safe, selective and stable.Conclusion: In this study, a combination of nanotechnology, organic synthesis and radiochemistry were utilized in order to design an efficient nano-system conjugated with a suitable radionuclide and an antitumor agent for possible application as tumor theragnostic agent.Four novel compounds (3 and 4a-c) bearing tetrahydroquinazoline-7-sulfonohydrazide or 1,2,3,4-tetrahydroquinazoline-7-sulfonamide scaffold were designed. Then, docking study predicted that the compounds can be considered as potential inhibitors for PARP-1. Following that; the four compounds were synthesized and properly characterized using 1HNMR, 13CNMR, IR and Mass spectroscopy. The cytotoxic effect of the four compounds was evaluated against breast cancer cell line (MDA-MB-436), where compound 3 showed the most promising cytotoxic effect. The inhibitory effect of the four compounds was evaluated in vitro against PARP-1.Carboxylated graphene oxide nanosheets (NGO-COOH) were synthesized by a modified Hummer's method and has size of range 40 nm. The NGO-COOH nanosheets were proven to be safe and biocompatible when tested in vitro against normal human lung fibroblast cells (MRC-5). The prepared NGO-COOH nanosheets were conjugated with compound 3 then radiolabeled with 99mTc to yield 99mTc-NGO-COOH-3 with a radiochemical yield of 98.5.0 ± 0.5%. 99mTc-NGO-COOH-3 was injected intravenously in solid tumor bearing mice to study the degree of localization of the nano-system at tumor tissue. The results of the study revealed, excellent localization and retention of the designed nano-system at tumor tissues with targeting ratio of 9.0.Stirred a new candidate tumor theragnostic agent that is safe, selective and stable.Graphical abstract: In this study, a combination of nanotechnology, organic synthesis and radiochemistry were utilized in order to design an efficient nano-system conjugated with a suitable radionuclide and an antitumor agent for possible application as tumor theragnostic agent.Four novel compounds (3 and 4a-c) bearing tetrahydroquinazoline-7-sulfonohydrazide or 1,2,3,4-tetrahydroquinazoline-7-sulfonamide scaffold were designed. Then, docking study predicted that the compounds can be considered as potential inhibitors for PARP-1. Following that; the four compounds were synthesized and properly characterized using 1HNMR, 13CNMR, IR and Mass spectroscopy. The cytotoxic effect of the four compounds was evaluated against breast cancer cell line (MDA-MB-436), where compound 3 showed the most promising cytotoxic effect. The inhibitory effect of the four compounds was evaluated in vitro against PARP-1.Carboxylated graphene oxide nanosheets (NGO-COOH) were synthesized by a modified Hummer's method and has size of range 40 nm. The NGO-COOH nanosheets were proven to be safe and biocompatible when tested in vitro against normal human lung fibroblast cells (MRC-5). The prepared NGO-COOH nanosheets were conjugated with compound 3 then radiolabeled with 99mTc to yield 99mTc-NGO-COOH-3 with a radiochemical yield of 98.5.0 ± 0.5%. 99mTc-NGO-COOH-3 was injected intravenously in solid tumor bearing mice to study the degree of localization of the nano-system at tumor tissue. The results of the study revealed, excellent localization and retention of the designed nano-system at tumor tissues with targeting ratio of 9.0.Stirred a new candidate tumor theragnostic agent that is safe, selective and stable. [ABSTRACT FROM AUTHOR]

Trazodone was labeled with 99mTc by indirect method. More than 97% radiochemical yield was reached under the following optimized conditions: 100 µg of Trazodone, pH 7, 10 mg of glucoheptonate, 35 µg of stannous chloride, 185 MBq of 99mTc eluate, 20 min, room temperature. The in vitro stability and also the retention of the complex in the brain tissue allow the use of this complex as a potential brain imaging agent. [ABSTRACT FROM AUTHOR]

A new production method of 99mTc using a high-current solid target was tested. The separation and purification setup was developed to produce high quantity and high specific activity of 99mTcO4− suitable for labeling various ligands for nuclear medicine imaging. A semiautomated target dissolution and separation system has been developed for 99mTcO4− production. The separation is based on a chromatographic column system. The chemical and radiochemical purity was found to be in accordance with the US and European Pharmacopoeia specifications. 99% of activity in the final product belonged to 99mTc. Less than 1% of the 99mTc activity was not incorporated in the target product with MDP kits. Biodistribution data for the labeled MDP kits show that the quality of the produced 99mTc-pertechnetate is identical to that of the pertechnetate from 99Mo/99mTc generators. The application of 99mTc-ethylenedicysteine in human proves the good quality of the produced Na99mTcO4. [ABSTRACT FROM AUTHOR]

In order to select a chelator with excellent stability, easier radiolabeling process and low cost, GRPr antagonist RM26 with the amino acid based chelator was radiolabeled with technetium-99m. The stability of the radiolabeled peptides in PBS, serum as well as in the presence of excess cysteine was compared. [ABSTRACT FROM AUTHOR]

To develop novel 99mTc labeled nitroimidazole imaging agents for imaging tumor hypoxia, 99mTc labeled ethylene diamine tetraacetic acid derivative of 4-nitroimidazole was reported by us earlier, which showed disadvantage of an unsatisfactory tumor-to-blood ratio. Therefore, 2-nitroimidazole was adopted as a pharmacophore to synthesize EDTA-2-EtNHNM, which was radiolabeled with 99mTc in high yield to achieve 99mTc-EDTA-2-EtNHNM. 99mTc-EDTA-2-EtNHNM was hydrophilic and exhibited good in vitro stability. Cellular experiment demonstrated its hypoxic selectivity while biodistribution results showed improved tumor-to-blood and tumor-to-muscle ratios. SPECT imaging studies of 99mTc-EDTA-2-EtNHNM indicated obvious accumulation in tumor, suggesting its potential to be a radiotracer for imaging tumor hypoxia. [ABSTRACT FROM AUTHOR]

We herein report a convenient radiolabeling method capable of real-time in vivo imaging and biodistribution of bacteria in a living subject. Escherichia coli (E. coli), a model microorganism in this study, was incubated with technetium-99m (99mTc) tricarbonyl under physiological conditions provided radiolabeled bacterial cells. 99mTc-labeled bacterial cells were obtained in high yield (42%, n = 5) and purity (> 99%) within 30 min. In vitro radiolabeling study using cellular components revealed that 99mTc could be incorporated with cytosolic proteins and it was maintained stably in E. coli under several media including mouse serum, high salt solutions with varying pH. SPECT/CT images and organ biodistribution of 99mTc-labeled bacterial cells showed quantitative in vivo behavior and accumulation of E. coli in mice. The radiolabeling method demonstrated here will be a promising platform tool for in vivo tracking and biodistribution of infectious microorganism. [ABSTRACT FROM AUTHOR]

The Korea Research Institute of Standards and Science (KRISS) participated in the BIPM.RI(II)-K4.Tc-99 m comparison of activity measurements of 99mTc. We develop the national primary standard for 99mTc solution used during the comparison. We use two primary liquid scintillation counting techniques for the standardization: digital coincidence counting with the 4πβ(LS)-γ(NaI(T1))system and triple-to-double coincidence ratio counting. Both methods give consistent results for the specific activity of a 99mTc solution. Adopting the result from the DCC method as the reference value of the 99mTc measurement, we evaluate the standard uncertainty of 0.856% for the KRISS primary standard of the 99mTc activity. The K4 comparison result shows that the newly-established KRISS primary standard lies within the standard uncertainty with the key comparison reference value defined from other 99mTc measurements. [ABSTRACT FROM AUTHOR]

Timonacic acid (TCA) was labeled with 99mTc in the presence of three different reducing agents: NaBH4, Na2S2O4, and SnCl2·2H2O. The optimum conditions were as follows: with Na2S2O4, pH 8, 7 mg of Na2S2O4, room temperature, 2 mg of TCA, 30 min (radiochemical yield 98 ± 0.3%, complex was stable for 24 h); with NaBH4, pH 8, 10 mg of NaBH4, room temperature, 2 mg of TCA, 30 min (radiochemical yield 95 ± 0.3%, complex was stable for 6 h). The biodistribution of the complex in mice was studied. The liver uptake depends on the reducing agent used, reaching in 30 min 33.5 ± 0.3, 18.4 ± 0.18, and 22.3 ± 0.3% ID/g for the complexes prepared using Na2S2O4, NaBH4, and SnCl2·2H2O, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Contrast-enhanced ultrasound plays an expanding role in oncology, but its applicability to molecular imaging is hindered by a lack of nanoscale contrast agents that can reach targets outside the vasculature. Gas vesicles (GVs)-a unique class of gas-filled protein nanostructures-have recently been introduced as a promising new class of ultrasound contrast agents that can potentially access the extravascular space and be modified for molecular targeting. The purpose of the present study is to determine the quantitative biodistribution of GVs, which is critical for their development as imaging agents.Procedures: We use a novel bioorthogonal radiolabeling strategy to prepare technetium-99m-radiolabeled ([99mTc])GVs in high radiochemical purity. We use single photon emission computed tomography (SPECT) and tissue counting to quantitatively assess GV biodistribution in mice.Results: Twenty minutes following administration to mice, the SPECT biodistribution shows that 84 % of [99mTc]GVs are taken up by the reticuloendothelial system (RES) and 13 % are found in the gall bladder and duodenum. Quantitative tissue counting shows that the uptake (mean ± SEM % of injected dose/organ) is 0.6 ± 0.2 for the gall bladder, 46.2 ± 3.1 for the liver, 1.91 ± 0.16 for the lungs, and 1.3 ± 0.3 for the spleen. Fluorescence imaging confirmed the presence of GVs in RES.Conclusions: These results provide essential information for the development of GVs as targeted nanoscale imaging agents for ultrasound. [ABSTRACT FROM AUTHOR]

1-Hydroxy-2-(2-pyridyl)ethanedisphosphonic acid monosodium salt (HPEDP) was prepared and labeled with 99mTc using two different reducing agents: SnCl2·2H2O and NaBH4; NaBH4 gave better results. The radiochemical purity of 99mTc(NaBH4)-HPEDP was 96 ± 4%, and the complex was stable in vitro for 6 h. The in vivo biodistribution studies performed in mice show highly selective uptake of the labeled compound in the skeletal system and rapid elimination via the urinary pathway. The maximum bone uptake was 32.3 ± 2.1% ID/organ. [ABSTRACT FROM AUTHOR]

A method for preparing 99mTc-Dacarbazine, a potential cancer diagnostic agent, was developed. The method is based on direct labeling of Dacarbazine with 99mTc in the presence of stannous chloride as reducing agent. The reaction conditions were optimized to obtain the radiochemical yield of 99mTc-Dacarbazine higher than 90%. The biodistribution of 99mTc-Dacarbazine in normal and tumor-bearing Albino Swiss mice was studied. 99mTc-Dacarbazine has a high tumor affinity and shows promise for cancer imaging. Quantitative relationship between the optimized structures and computed molecular properties related to Dacarbazine binding sites was analyzed using molecular modeling. [ABSTRACT FROM AUTHOR]

Abstract: The development of systems that can prevent infections and also ensure bone integration as well as regeneration have been of great interest for pharmaceutical technology. In this study, we show the synthesis of surface-functionalized mesoporous silica (SBA-16) and silica composed of calcium phosphate (SBA-16/HA) particles in order to be applied as efficient drug delivery carriers. The particles were synthesized, functionalized with 3-aminopropyltriethoxysilane (APTES) by post-synthesis grafting and loaded with the osteomyelitis antibiotic agent ciprofloxacin. Moreover, the diethylenetriaminepentacetic acid (DTPA) was anchored in silica-APTES to allow measurements of biological process at molecular and cellular levels. Particles were physicochemically characterized by small angle X-ray scattering (SAXS), elemental analysis (CHN), thermogravimetric analysis (TGA), N2 adsorption and zeta potential analysis. Functionalized silica particles were radiolabeled with technetium-99m showing high radiochemical yields and high radiolabeled stability. In vivo experiments results showed higher bone uptake of the SBA-16/HAAPTES than SBA-16APTES. In addition, bactericidal efficacy of these particles was tested against microorganisms present in bone infection, and our composites had bactericidal efficiency comparable to free-ciprofloxacin. In summary, taking into account the great potential of these silica mesoporous and nanocomposite structures to carry molecules, besides their bactericidal efficacy, these materials are promising candidates for bone infection treatment.Graphical abstract: [ABSTRACT FROM AUTHOR]

Uridine, a pyrimidine nucleoside essential for the synthesis of RNA and biomembranes, was radiolabeled with 99mTc to obtain a potential tumor imaging agent. The maximal radiochemical yield of about 96.5%, as determined by paper chromatography and instant thin-layer chromatography, was reached under the following optimum conditions: 1 mg of uridine, 20 µg of SnCl2·2H2O as reducing agent, 20 mg of mannitol as a stabilizer, and pH 8. 99mTc-uridine is stable in vitro at room temperature for up to 6 h post labeling. The biodistrbution study in tumor-bearing mice shows high target-to-nontarget ratio. These results match with the high docking score of the complex on uridine phosphorylase enzyme. 99mTc-uridine shows promise as a tumor imaging agent. [ABSTRACT FROM AUTHOR]

Tc-oxiracetam was prepared. It can be used as a radiotracer for brain imaging. Under the optimum conditions (0.5 mg of oxiracetam, 50 μg of SnCl·2HO, pH 7, room temperature, 30 min), the radio-chemical yield determined by chromatographic methods reached 96%. Biodistribution studies with mice showed that the brain uptake of the complex was 5.1% injected dose per gram (% ID/g) at 5 min post injection. In this parameter, the complex surpasses the commercially available Tc-ECD (4.7% ID/g) and Tc-HMPAO (2.25% ID/g). [ABSTRACT FROM AUTHOR]

The design and synthesis of ethyl 4-(6-amino-7-cyano-2,3-dihydro-1 H-pyrrolizine-5-carboxamido)-benzoate (KH16) were discussed, and its structure was determined. The anti-inflammatory activity of a new compound was evaluated using in vitro cyclooxygenase (COX) inhibitory assay. KH16 exhibits higher selectivity to COX-2 than to COX-1 with the selectivity index of 3.46. KH16 was labeled with Tc with the maximum radiochemical yield of Tc-KH16 of 90.5 ± 1.5%. Biodistribution of Tc-KH16 in normal, infected, and inflamed mice was studied. The uptake in inflamed muscle was higher than that in normal muscle throughout the examined time interval. This work is a step ahead in the direction of using pyrrolizine derivatives for site-specific delivery to the inflamed tissue. [ABSTRACT FROM AUTHOR]

Sentinel lymph node (SLN) mapping in endometrial cancer (EMCA) is rapidly gaining acceptance in the clinical community. As compared to a full lymphadenectomy in every patient, to a selective lymphadenectomy after frozen section of uterus in selected patients with intrauterine risk factors or to a strategy in which a lymphadenectomy is always omitted, SLN mapping seems to be a reasonable and oncologically safe middle ground. Various protocols can be used when applying an SLN mapping. In this manuscript we review the characteristics, toxicity and clinical impact of technetium-99m radiocolloid (Tc-99m), of the blue dyes (methylene blue, isosulfan blue and patent blue) and of indocyanine green (ICG). ICG has an excellent toxicity profile, has higher overall and bilateral detection rates as compared to blue dyes and higher bilateral detection rates as compared to a combination of Tc-99m and blue dye. The detrimental effect of BMI on the detection rates is attenuated when ICG is used as a tracer. The ease of use of the ICG SLN mapping is perceived by the patients as a better quality of care delivered. Whenever possible, ICG should be favored over the other tracers for SLN mapping in EMCA patients. [ABSTRACT FROM AUTHOR]

A radiotracer investigation was carried out to characterize flow dynamics of liquid phase in a pulsed sieve plate column (PSPC). Technetium-99m as sodium pertechnetate was selected and used as a radiotracer. Residence time distribution of liquid phase was measured at different operating conditions. Two different mathematical models i.e. axial dispersion and tanks-in-series with backmixing models were used to simulate the experimental data. Analysis of the experimental data revealed that flow of liquid in the PSPC can be approximated as an axially dispersed plug flow. [ABSTRACT FROM AUTHOR]

Bacterial infection is one of the vital reasons of morbidity and mortality, especially in developing countries. It appears silently without bothering the geological borders and imposes a grave threat to humanity. Nuclear medicine technique has an important role in helping early diagnosis of deep-seated infections. The aim of this study was to develop a new radiopharmaceutical Tc-labeling sulfadiazine as an infection imaging agent. Radiolabeling of sulfadiazine with technetium-99m (Tc) was carried out using stannous tartrate as a reducing agent in the presence of gentistic acid at pH = 5. The quality control tests revealed ~98% labeling efficiency. Paper chromatographic (PC) and instant thin-layer chromatographic (ITLC) techniques were used to analyze radiochemical yield. Biodistribution and infection specificity of the radiotracer were performed with Escherichia coli ( E. coli) infection-induced rats. Scintigraphy and glomerular filtration rate (GFR) study was performed in E. coli-infected rabbits. Scintigraphy indicated E. coli infection targeting potential of Tc-SDZ, while biodistribution study showed minimal uptake of Tc-SDZ in non-targeted tissues. The uptake in the kidneys was found 2.56 ± 0.06, 2.09 ± 0.10, and 1.68 ± 0.09% at 30 min, 1 h, and 4 h, respectively. The infected muscle (target) to non-infected muscle (non-target) ratio (T/NT) was found 4.49 ± 0.04, 6.78 ± 0.07, and 5.59 ± 0.08 at 30 min, 1 h, and 4 h, respectively. [ABSTRACT FROM AUTHOR]