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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 mu g/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. [GRAPHICS] ., Ege University Research Fund [2018 FBE 006]; NIH/NCI Cancer Support Grant [P30 CA008748], This work was financially supported by Ege University Research Fund (2018 FBE 006) and partially presented at HEZARFEN International Congress of Science, Mathematics, and Engineering Sciences held in Izmir/Turkey on November 8-10, 2019. Dr. Omer Aras was partially supported through the NIH/NCI Cancer Support Grant P30 CA008748.

Nanoparticles are frequently used as targeting delivery systems for therapeutic and diagnostic radiopharmaceuticals. Polyethylene oxide-polyacrylic acid (PEO-PAAc) nanogel was prepared via γ-radiation-induced polymerization. Variable factors affecting nanoparticles size were investigated. The nanogel was radiolabeled with the imaging radioisotope 99m Tc and finally conjugated with folic acid to target folate receptor actively. PEO-PAAc-folic acid gel was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). Biodistribution was studied in normal mice and solid tumor-bearing mice via intravenous and intratumor injections of the radiolabeled PEO-PAAc-folic acid nanogel. Results of biodistribution showed high selective uptake of the prepared complex in tumor muscle compared with normal muscle for both intravenous and intratumor injections. The T/NT ratio was found to be 6.186 and 294.5 for intravenous and intratumor injections, respectively. Consequently, 99m Tc-PEO-PAAc-folic acid complex could be a promising agent for cancer diagnostic imaging.

Background and Design: Psoriasis is a common chronic inflammatory skin disease believed to affect renal functions. Glomerular filtration rate (GFR) is the most important indicator used to assess renal functions. The present study aims to measure the renal function of psoriasis patients via the technetium-99m diethylenetriamine pentaacetate (Tc-99m DTPA) method and compare the values obtained with those determined through indirect measurement methods, such as the modification of diet in renal disease (MDRD) and chronic kidney disease epidemiology collaboration (CKD-EPI), considering the effects of systemic treatments and comorbidities. Materials and Methods: Eighty-seven patients diagnosed with chronic plaque-type psoriasis vulgaris were included in this study. The patients’ demographic characteristics, disease duration, psoriasis area and severity index score, drugs received for psoriasis treatment, comorbidities, and drugs received for comorbidity treatment were noted. Estimated GFRs were also calculated using the MDRD and CKD-EPI formulas. Results: Tc-99m DTPA values were affected only by age. As the patient age increased, a significant decrease in GFR measured with Tc-99m DTPA (r=0.289, p

Objective: To determine the normal value of thyroid Technetium-99m uptake value in a single centre Pakistani population. Study Design: Cross-sectional study. Place and Duration of Study: Nuclear Medical Centre, Armed Forces Institute of Pathology, Rawalpindi, from Feb 2019 to Apr 2020. Methodology: A total of 90 patients who presented to Nuclear Medical Centre for parathyroid dual radiopharmaceutical scintigraphy were included in study and selected by non-probability consecutive sampling technique. Thyroid uptake studies were calculated via gamma camera acquisition. Pre injection counts were taken from the Technetium-99m pertechnetate filled syringe, thyroid counts were taken from the anterior thyroid image 20 minutes post injection and to look for any residual radiopharmaceutical counts of the empty syringe were also taken. Results: Out of total of 90 patients, 32 (35.6%) were male while 58 (64.4%) were female with male to female ratio of 1:2. The mean age was 38.4 ± 12.7. Mean Thyroid Stimulating Hormone values were 1.6 ± 0.8 and mean T4 values were 11.9 ± 3.5. The 5th-95th percentile range was 0.4-2.2% and median was 1.2%. The interquartile range was calculated to be 0.9-1.5%. Conclusion: Normal value of thyroid Technetium-99m uptake value in a single centre Pakistani population values varies significantly as compared to global figures i.e. 0.3-4.5% and is different than the one used in our own department i.e. 0.5-2.0%.

Purpose: To prepare technetium-99m (99mTc)-labelled nanogel loaded with 5-fluorouracil (5-FU) containing synthesized gallic acid-stearylamine (GA-SA) conjugate in order to reduce its systemic toxicity and provide site-specific delivery to skin lesions. Methods: Lipid nanocarrier-based 1 % (w/w) 5-FU nanogel containing GA-SA conjugate was successfully formulated. Parameters that included pH, viscosity and entrapment efficiency were measured. Furthermore, 1 % (w/w) 5-FU nanogel and 1 % (w/w) 5-FU commercial formulations were radiolabelled with 99mTc. The radiolabelled 99mTc-5-FU nanogel and commercial formulations were subjected to successive preclinical assessments with respect to radiochemical stability, biodistribution, and gamma scintigraphy in BALB/c mice, and pharmacokinetic studies in New Zealand albino rabbits. Results: The entrapment efficiency of 5-FU in the nanogel preparation was 82.12 ± 1.2 %. The 5-FU nanogel formulation exhibited excellent radiolabelling efficiency (> 93 %) and high stability. Skin/blood localization ratios of 274.93 and 167.89 were obtained for topical radiolabelled drug-loaded 5-FU nanogel formulation and 5-FU commercial formulation, respectively, after 1 h of administration. Gamma scintigraphy and biodistribution studies showed that topically administered 99mTc-5-FU nanogel was distributed mostly in skin, when compared to marketed 5-FU formulation. Pharmacokinetic studies revealed low maximum activity in the blood (Cmax = 34.20 µg/mL), with low intensity (AUC) for topically administered 99mTc-5-FU nanogel formulation. Conclusion: 5-FU nanogel enhances specific delivery of 5-FU at targeted sites and decreases its toxicity in tissues distant from the site of application. The results suggest that nanogel loaded with 5-FU containing synthesized GA-SA conjugate is a novel effective approach for the treatment of skin lesions.

Thalidomide is a sedative drug discovered at the end of the 50s, it showed high anticancer activity so attempts were made to synthesize thalidomide analogs that had fewer side effects than the parent compound. DPDQA showed higher anticancer activities than thalidomide. Labeling of a DPDQA with 99mTc using Na2S2O4 as reducing agent was performed. The dependence of the radiolabeling yield on the concentrations of DPDQA and reducing agent, pH of the reaction mixture, reaction time, and reaction temperature was studied. Bio-distribution studies in mice with tumor induced in the right thigh were carried out. The tumor infected thigh/contralateral thigh uptake ratio (T/NT) was evaluated. The time for the maximum accumulation of the 99mTc–DPDQA in the tumor site was evaluated after administration of the compound.

Objective To determine the frequency of pyramidal lobe remnants after total thyroidectomy (TT) and the effect on stimulated thyroglobulin (Tg). Methods The study included 1740 differentiated thyroid cancer (DTC) patients who were followed up by our center. The department database was searched to identify DTC patients with residual pyramidal lobe after TT. All postoperative technetium-99m pertechnetate thyroid scintigraphy images were re-evaluated for pyramidal lobe residue. Serum stimulated Tg and thyroid stimulating hormone (TSH) levels measured within the first 6 months after TT were retrieved from the database. Results Pyramidal lobe residue was detected in 10.4% of the patients who underwent TT. Evidence of the pyramidal lobe was present on preoperative ultrasonography in 1.6% of the patients with residual pyramidal lobe. Stimulated Tg in patients with pyramidal lobe residue was significantly higher than that in patients without residue (P = .01). Endogenous stimulated TSH in patients with residual pyramidal lobe was significantly lower than that in patients without residue (P = .036). In 5.7% of patients with pyramidal lobe residue, a TSH level of >30 mIU/L was not achieved, which was a significantly higher rate than that in patients without pyramidal lobe residue (P = .034) and is the level required for maximum radioiodine uptake. Conclusion Pyramidal lobe residue was found in almost 10% of DTC patients. The pyramidal lobe is often missed on preoperative ultrasonography. Residual pyramidal lobe increased stimulated Tg and decreased endogenous stimulated TSH. Residual pyramidal lobe may complicate the follow-up of DTC patients.

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.

Polyvinylpyrrolidone (PVP) is a biopolymer compound that has been widely used in pharmaceutical and medical applications, especially as a tablet binder and solubilizing agents for injections. In th...

The research objective is to design intranasal (IN) brain targeted CLZ-loaded polymeric nanomicellar systems (PNMS) aiming to improve central systemic CLZ bioavailability. Direct equilibrium method was used to prepare CLZ-PNMS using two hydrophobic poloxamines; Tetronic® 904 (T904) and Tetronic® 701 (T701) and one hydrophilic poloxamer; Synperonic® PE/F127 (F127). Optimization is based on higher percent transmittance, solubilizing efficiency, and in vitro release after 24 h with smaller particle size was achieved using Design-Expert® software. The optimized formula was further evaluated via TEM, ex vivo nasal permeation in addition to in vivo biodistribution using radiolabeling technique of the optimized formula by Technetium-99m (99mTc). The optimized formula M5 has small size (217 nm) with relative high percentage of transmittance (97.72%) and high solubilization efficacy of 60.15-fold following 92.79% of CLZ released after 24 h. Ex vivo nasal permeation showed higher flux of 36.62 μg/cm2.h compared to 7.324 μg/cm2.h for CLZ suspension with no histological irritation. In vivo biodistribution results showed higher values of radioactivity percentage of the labeled optimized formula (99mTc–M5) in brain and brain/blood ratio following IN administration of 99mTc–M5 complex which were greater than their corresponding values following intravenous route. It is obvious that nasal delivery of CLZ-PNMS could be a promising way to improve central systemic CLZ bioavailability.

Most important quality attributes of any radiopharmaceutical (RPh) are its radiochemical purity (RCP) or content of radiochemical impurities (RCIs) that have to comply with respective norms and limits. However, at present, there is no unified approach to validation of analytical methods in the context of highly radioactive samples.The aim of the study was to develop an approach to validation of methods for determination of RCI content in RPhs.Materials and methods: the authors determined the content of RCIs in a radiopharmaceutical formulation containing a complex of technetium-99m and methylenediphosphonic acid by the radiometric method after isolation of impurities from the main compound by thin-layer chromatography using silica gel and methyl ethyl ketone (for sodium pertechnetate determination) and silica gel and 13.6% sodium acetate solution (for determination of hydrolysed reduced technetium-99m). The radioactivity was registered by a chromatogram scanner with a detector of gamma-rays with energies from 0.05 to 1.5 MeV.Results: the paper analyses existing official approaches to validation of analytical procedures and compares them with the results of experimental studies described in available publications. It assesses the validation parameters for compliance with the acceptance criteria set forth in the current regulations and substantiates selectivity of chromatographic determination of impurities under the selected test conditions. Coefficients of variation for repeatability, reproducibility, and accuracy did not exceed 4.5, 2.8, and 8.9%, respectively, given the relative error of not more than 10.5%. The study demonstrated signal linearity for the 10-fold dilution of the standardised sodium pertechnetate solution, it also demonstrated correspondence between the applied and detected radioactivity when performing the test in the impurity content range of 0.5–5%. The validation procedure was associated with significant radiation burden for the personnel of the quality control laboratory.Conclusions: the authors suggested a methodological approach to validation of methods for determination of RCI content in technetium-99m-based RPhs. This approach may be used in the development of a guideline on validation of analytical methods for RCP/RCI determination in RPhs, or for introduction of relevant sections into existing documents.

In the 1980s, 201Tl scintigraphy helped to introduce noninvasive assessment of myocardial perfusion as an important clinical tool for the detection and management of coronary artery disease (CAD). Monovalent cations such as 201Tl exhibit pharmacokinetics that are very suitable for the assessment of

Introduction. Skin cancers came first in Russia in numbers of oncological diseases. Melanoma, making up only a small part of these cases, leads to the most serious consequences. The nuclear medicine methods application is necessary at the stages of clarifying the diagnosis, searching for remote metastases and the treatment monitoring. The work is devoted to one of the stages of the radiopharmaceutical development for the diagnostics of malignant melanoma and its metastases based on the synthetic analog of α-melanocyte stimulating hormone (SAH) and radionuclide Tc-99m.Aim. The selection of optimal conditions for the preparation of the SAH ∙ 99mTc complex and the study of the using possibility it as a diagnostic tool in in vitro experiments.Materials and methods. Experimental work was carried out to optimize the conditions for obtaining the complex compound SAH ∙ 99mTc. The binding and internalization of this compound by B16-F0 melanoma cells has been studied.Results and discussion. The results of labeling SAH with a 99mTc radionuclide under a wide range of conditions were obtained both by the direct method and using the intermediate complex. The target compound rapidly binds to B16-F0 melanoma cells. The degree of internalization is more than 85 %.Conclusion. Based on the results of chemical experiments and data from in vitro experiments, optimal conditions for obtaining a complex compound SAH ∙ 99mTc with a radiochemical yield of more than 90 % were found. The mechanism of binding of this compound to malignant melanoma cells has been established.

The aim of this study was to prepare radiolabeled peptide-based agents for imaging of colon cancer. According to the incorporation of HYNIC for radiolabeling with technetium-99m, two analogs were designed and compared: an antitumor-antibody-derived peptide based on the EPPT sequence and a novel retro-inverso peptidomimetic derivative D (TPPE) structurally modified by replacing the L-amino acids with D-amino acids and reversing the primary amino acid sequence of EPPT. The HYNIC-conjugated peptides were labeled with 99m Tc using tricine/EDDA coligand with more than 98% radiochemical yield and showed high metabolic stability. Kd values of 41.77 ± 7.34 nM and 37.33 ± 8.37 nM for 99m Tc-HYNIC-EPPT and 99m Tc-HYNIC-D (TPPE) confirmed high affinity of both peptides for cell surface antigen MUC1. These radiotracers demonstrated no significant differences in the cellular uptake and internalization value, but the biodistribution profile of 99m Tc-HYNIC-D (TPPE) was more favorable than that of 99m Tc-HYNIC-EPPT as a result of better tumor-to-non-target ratios for the examined tissues and organs. HT29 tumors were visualized more clearly in scintigraphic images with 99m Tc-HYNIC-D (TPPE) in comparison with 99m Tc-HYNIC-EPPT. The results showed the retro-inverso analog to be a more promising radiotracer as a probe for in vivo targeting of HT-29 tumors than the parent peptide.

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

The aim of this study is to find the optimum conditions of labeling luteolin flavonoid compounds with technetium-99m (99mTc) to meet the purity requirements stated in the United States Pharmacopeia. This compound is expected to be a potential radiotracer compound for diagnosing cancer. The optimization method in labeling luteolin with technetium determines the parameters such as pH, SnCl2.2H2O, genistein concentration, and incubation time. Optimization results of Technetium-99m-luteolin labeling obtained optimum pH conditions 8, the amount of SnCl2.2H2O as a reducing agent 60 μL, the optimum amount of luteolin 6 mg/ml, and the optimum incubation time is 30 min. This optimum condition obtained a 99mTc-Luteolin radiochemical purity yield of 94.15%. The radiochemical purity percentage of the 99mTc-Luteolin compound has fulfilled the requirements listed at United States Pharmacopeia, which is ≥90%.

BACKGROUND The indocyanine green retention rate at 15 min (ICGR15) is a gold standard parameter of liver function when deciding on the extent of hepatectomy. However, ICGR15 is influenced by several hepatic conditions. To evaluate auxiliary preoperative liver functional reserve, we examined the clinical significance of modified parameters by blood tests and technetium-99m galactosyl human serum albumin (Tc-GSA) scintigraphy. METHODS We measured liver function parameters, including the hepatic uptake ratio (LHL15) and the blood pool clearance index (HH15) of Tc-GSA and their modified formulae [LHL/HH15, LHL minus HH15, and converted ICGR15 (cICGR15) from a preliminary study] in 229 patients, including 18 with biliary obstruction. RESULTS The mean values of LHL15/HH15, LHL minus HH15, and cICGR15 were 1.646 ± 0.295, 0.347 ± 0.116, and 13.2 ± 5.3%, respectively. These parameters correlated significantly with other liver functions measured by blood tests except for the bilirubin level (P

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.

Silver tungstate nanoparticles have been presenting attractive characteristics that could allow its usage in the biomedical sciences. In this study, Ag2WO4 nanoparticles with an average size of 242 nm were obtained and radiolabeled with technetium-99m with high labeling-yield as well as high stability. Biodistribution studies were carried out in healthy and tumor-bearing mice to determine the nanoparticle’s in vivo behavior. The results revealed an important tumor-to-muscle ratio, reaching values above than 1.5, demonstrated the ability of this nanomaterial in accumulating preferentially in tumor tissue. All results together, converge to consider the Ag2WO4 nanoparticles as a potential system against cancer and a potential new radiolabeled probe for tumor identification and uptake.

Currently the development of technologies for labeling somatostatin with technetium-99m for diagnosing radionuclide neuroendocrine tumors is under way. Somatostatin analogues are binded with technetium99m only by the preliminary addition of a chelating agent. Therefore, it is important to develop a method for preparation of an octreotide derivative by modifying octreotide with precursors: ligands with high chelating ability for its tight binding with technetium-99m. ω-Bis(pyridin-2-ylmethyl)amino)aliphatic acids can be used successfully as such precursors.The purpose of the study was to develop a method for obtaining a new octreotide derivative for diagnosing neuroendocrine tumors.Materials and methods. The somatostatin octreotide analogue was used as the object of the study; succinimid-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used as a chelating agent. Methods of high performance liquid chromatography and mass spectrometry were used to separate and analyze the synthesized compounds.Results. A method to produce an original octreotide derivative using a succinimid-1-yl 6-(bis(pyridin2-ylmethyl)amino)hexanoate as a chelating agent was proposed. The conditions of analytical and semipreparative HPLC for the analysis and purification of the active octreotide derivative (a monosubstituted derivative of the amino acid residue of D-phenylalanine) were suggested.Conclusion. The synthesized derivative of octreotide has a chelating center for strong binding to technetium-99m in its structure, which can be useful for diagnosing neuroendocrine tumors.

Purpose: To study the features of the distribution and removal of a new radiopharmaceutical (RPH) on the basis of a labeled 99mTc glucose derivative for radionuclide diagnostics of oncological diseases in the body of experimental animals. Material and methods: The main stage of the study was performed on 65 mature conventional outbred white rats and 9 rabbits of the Soviet Chinchilla breed. To study the dynamics of changes in the concentration of the studied RPH in the blood plasma and its distribution in the main organs and tissues, as well as to study the metabolic features of the drug and its excretion, the RPH studied was administered intravenously, once in activity of 20 MBq. Multiple introduction of the RPH was performed in order to study the cumulative properties of the study drug, and to elucidate the possibilities of predicting the cumulation processes from the data obtained with a single administration of RPH. For this purpose, intravenous RPH was administered at the same time 1 time / day for 5 days, at a dose of 20 MBq. To confirm the theory of linearity of the pharmacokinetics of the RFP studied, three groups of laboratory animals received the drug in three activity levels – 10, 20 and 40 MBq were used. After euthanasia, the animals were autopsied and removed the necessary organs and tissues. The prepared and washed organs were placed in tubes for further radiometry in order to study the concentrations of the RPH in the bioassay. Results: It has been established that the RPH being studied practically does not accumulate in the main organs and tissues, accumulating mainly in the kidneys and bladder. The main organs of elimination of the test drug are the kidneys, and the main excreta are urine. The half-life of the drug from the blood was 10 minutes. Pharmacokinetics of the drug is linear and does not depend on the administered activity, and the drug itself does not possess cumulative properties. Conclusion: A study of the pharmacokinetics of the RPH 99mTc-1-Thio-D-glucose showed that the preparation possesses optimal properties for the diagnostic agent. The drug stably does not accumulate in the main organs and tissues, which allows it to be reused, for example at the stages of dynamic observation of cancer patients.

Radiotracers labelled with technetium-99m (99mTc) enable accessible diagnostic imaging of disease, provided that radiotracer preparation is simple. Whilst 99mTc radiopharmaceuticals for imaging perfusion are routinely prepared from kits, and regularly used in healthcare, there are no 99mTc-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 99mTc-labelled radiotracers: its conjugates are simple to prepare and can be easily labelled with 99mTc using one-step, kit-based protocols. Here, reaction of BMA with the αvβ3-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 99mTcO4- to this kit, followed by heating, furnished the radiotracer [99mTcO2(DP-RGD)2]+ in consistently high radiochemical yields (>90%). The analogous [ReO2(DP-RGD)2]+ compound was prepared and characterised, revealing that both [99mTcO2(DP-RGD)2]+ and [ReO2(DP-RGD)2]+ consist of a mixture of cis and trans geometric isomers. Finally, [99mTcO2(DP-RGD)2]+ exhibited high metabolic stability, and selectively targeted αvβ3-integrin receptors, enabling in vivo SPECT imaging of αvβ3-integrin receptor expression in mice.

The trend to achieve even more compact-sized systems is leading to the development of micro-scale reactors (lab-on-chip) in the field of radiochemical separation and radiopharmaceutical production. Technetium-99m extraction from both high and low specific activity molybdenum could be simply performed by MEK-driven solvent extraction if it were not for unpractical automation. The aim of this work is to develop a solvent extraction and separation process of technetium from molybdenum in a micro-scale in-flow chemistry regime with the aid of a capillary loop and a membrane-based separator, respectively. The developed system is able to extract and separate quantitatively and selectively (91.0 ± 1.8% decay corrected) the [99mTc]TcO4Na in about 20 min, by using a ZAIPUT separator device. In conclusion, we demonstrated for the first time in our knowledge the high efficiency of a MEK-based solvent extraction process of 99mTc from a molybdenum-based liquid phased in an in-flow micro-scale regime.

BACKGROUND Technetium-99m-dimercapto succinic acid (Tc-99m DMSA) scintigraphy is a commonly used imaging modality in children with urological abnormalities. The radiopharmaceuticals, which have the effects of ionising radiation, are used in this method. This study aimed to investigate the impact of the Tc-99m DMSA scan on renal oxidative stress and mononuclear leukocyte (MNL) DNA damage. METHODS Children, who were followed up by paediatric nephrology at Bezmialem Vakif University and underwent Tc-99m DMSA scintigraphy between April 2015 and January 2016 with the indication of detection of renal scars, were included in this study. The exclusion criteria were nephrolithiasis, history of premature birth and recent urinary tract infection 3 months prior to scintigraphy or antibiotic use in the last 1 month. 3 mL heparinised blood samples were obtained just before, immediately after and 1 week after the scintigraphy. MNL DNA damage, total antioxidant status (TAS) and total oxidant status (TOS) were measured in the blood samples. The oxidative stress index (OSI) was calculated. Spot urine samples were obtained from each patient before and within 3 days after performing the scintigraphy. TAS/Creatinine (TAS/Cr), TOS/Creatinine (TOS/Cr) and N-acetyl-glucosaminidase/creatinine (NAG/Cr) levels were measured in the urine samples. RESULTS Twenty-seven children were evaluated. The values between TAS, TOS and OSI levels in serum samples at baseline, immediately after and 1 week after the scintigraphy (P = .105, P = .913, and P = .721, respectively) showed no statistically significant difference. The levels of TAS/Cr, TOS/Cr, NAG/Cr ratios and OSI, which were evaluated from urine samples before and within 3 days after the scintigraphy scan were also similar (P = .391, P = .543, P = .819 and P = .179, respectively). The levels of DNA damage only increased following scintigraphy scan and decreased a week later (P

Presented are the results of 99mTc and 101Tc production via neutron irradiation of natural isotopic molybdenum (Mo) with epithermal/resonance neutrons. Neutrons were produced using a deuterium-deuterium (D-D) neutron generator with an output of 2 × 1010 n/s. The separation of Tc from an irradiated source of bulk, low-specific activity (LSA) Mo on activated carbon (AC) was demonstrated. The yields of 99mTc and 101Tc, together with their potential use in medical single-photon emission computed tomography (SPECT) procedures, have been evaluated from the perspective of commercial production, with a patient dose consisting of 740 MBq (20 mCi) of 99mTc. The number of neutron generators to meet the annual 40,000,000 world-wide procedures is estimated for each imaging modality: 99mTc versus 101Tc, D-D versus deuterium-tritium (D-T) neutron generator system outputs, and whether or not natural molybdenum or enriched targets are used for production. The financial implications for neutron generator production of these isotopes is also presented. The use of 101Tc as a diagnostic, therapeutic, and/or theranostic isotope for use in medical applications is proposed and compared to known commercial nuclear diagnostic and therapeutic isotopes.

Funding Acknowledgements Type of funding sources: None. Background/Introduction Nuclear scintigraphy with bone-avid radiotracers such as Tc-99m-PYP, Tc99m-DPC and Tc-99m-HMDP are used to diagnose transthyretin (ATTR) cardiac amyloidosis with limited quantification employing a semi-quantitative visual score and a heart to contralateral lung ratio. Therapy for ATTR cardiac amyloid currently is limited to a single FDA approved agent, tafamidis, however, there is no data regarding the longitudinal assessment of imaging findings in patients undergoing therapy. SPECT/CT acquisition and analysis with dedicated software can provide volumetric assessment and quantification of cardiac tracer uptake. Purpose The purpose of this study was to perform longitudinal assessment of cardiac ATTR amyloid 99mTc-PYP imaging findings to determine if treatment with tafamidis results in any change in quantitative measures of tracer uptake. There is no data on if treatment results in a decrease in cardiac amyloid burden as assessed by 99mTc-PYP imaging. Methods A prospective, single center, study of patients with ATTR cardiac amyloid being treated with tafamidis (either 80mg or 61mg dose) who have baseline and follow-up 99mTc-PYP studies. SPECT/CT quantification software was used to quantify heart, lung, and bone tracer uptake and generate standardized uptake values (SUVs). Comparison of baseline (before treatment) total SUVs, mean SUV value, percentage of the injected dose, mean SUV of heart to mean SUV of bone ratio and to mean SUV of right lung ratio was made to the values obtained at follow-up after tafamidis treatment. Measurements were obtained from the whole heart and the isolated left ventricle. Data was obtained by two physicians and the results averaged. Results 5 patients were analyzed with a mean age 73.8 ± 7.7, 80% were males, and a mean length of tafamidis therapy at repeat imaging of 12.5 ± 3.8 months. At follow-up there was an average decrease in whole heart total SUV counts by -25.9 ± 10.3%, in the mean SUV value by -18.2 ± 18.2% and in the percentage of injected dose by -23.7 ± 14.0%. Similar decreases were seen in the isolated left ventricle measures. Heart to bone and heart to lung ratios showed a mixed response to therapy. Detailed results are provided in the table. Conclusion The measurements of total SUV counts, mean SUV value, and percentage of the injected dose showed improvement with tafamidis treatment. The ratios did not uniformly show improvement and the reason for this finding is unclear. This new technique offers a potential method for following tafamidis therapy and assessing the cardiac amyloid burden.

Background The fluorescent dye indocyanine green (ICG) has emerged as a promising tracer for intraoperative detection of sentinel lymph nodes (SLNs) in early‐stage cervical cancer. Although researchers suggest the SLN detection of ICG is equal to the more conventional combined approach of a radiotracer and blue dye, no consensus has been reached. Aims We aimed to assess the differences in overall and bilateral SLN detection rates with ICG versus the combined approach, the radiotracer technetium‐99m (99mTc) with blue dye. Methods and Results We searched MEDLINE, Embase, and the Cochrane Library from inception to January 1, 2020 and included studies reporting on a comparison of SLN detection with ICG versus 99mTc with blue dye in early‐stage cervical cancer. The overall and bilateral detection rates were pooled with random‐effects meta‐analyses. From 118 studies retrieved seven studies (one cross‐sectional; six retrospective cohorts) were included, encompassing 589 patients. No significant differences were found in the pooled overall SLN detection rate of ICG versus 99mTc with blue dye. Meta‐analyses of all studies showed ICG to result in a higher bilateral SLN detection rate than 99mTc with blue dye; 90.3% (95%CI, 79.8‐100.0%) with ICG versus 73.5% (95%CI, 66.4‐80.6%) with 99mTc with blue dye. This resulted in a significant and clinically relevant risk difference of 16.6% (95%CI, 5.3‐28.0%). With sensitivity analysis, the risk difference of the bilateral detection rate maintained in favor of ICG but was no longer significant (13.2%, 95%CI −0.8‐27.3%). Conclusion ICG appears to provide higher bilateral SLN detection rates compared to 99mTc with blue dye in patients with early‐stage cervical cancer. However, in adherence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, the quality of evidence is too low to provide strong recommendations and directly omit the combined approach of 99mTc with blue dye.

Background and Aims Glomerular filtration rate (GFR) is estimated traditionally from 24-hour urinary creatinine clearance. Creatinine is mainly filtered by glomerulus. The collection of 24-hour urinary sample is a difficult task with many patients fail to collect all the urine samples. As measuring GFR is cumbersome, expensive, and not easily available in all centers, various equations are developed for estimating GFR from creatinine like MDRD, CKD EPI creatinine. GFR obtained from serum creatinine shows wide variation as muscle mass and dietary protein intake are important determinants of serum creatinine concentration. Literature shows very few studies with GFR estimation with reference to age in Indian population. Hence, this study is planned to develop age specific nomogram for GFR in healthy kidney donor population as well as to study agreement between GFR obtained by 99m Tc DTPA three sample method and GFR estimated by 24-hour urinary creatinine. The aim of this stidy was to develop age-specific nomogram GFR in healthy kidney donor population and to study the agreement between the GFR measured by Technetium-99m diethylene triamine pentaacetic acid (99m Tc DTPA) and 24-hour urinary creatinine method. Method This study was conducted at Sir Ganga Ram hospital, New Delhi. All healthy individuals aged more than 20 years and less than 65 years, undergoing evaluation as prospective kidney donor at our hospital were the part of this study. GFR was measured by 99m Tc DTPA clearance using 3 sample method. GFR measured by DTPA method was used to develop nomogram. Creatinine Clearance was calculated from 24-hour urinary creatinine by formula U x V/P where, U is urinary creatinine level, P is plasma creatinine level and V is total volume of urine. Nomogram was developed with respect to these 3 Age groups; namely, 20 to 40 years, 40 to 50 years and 50 to 65 years Results Total 100 kidney donors were included in this study. Enrolled subjects were divided into 3 age groups; 20 to 40 years (n=28), 40 to 50 years (n=46) and 50 to 65 years (n=26). Majority of the donors were females (n=80). The agreement between GFR obtained by 99m Tc DTPA and 24-hour urinary creatinine clearance methods was 92.6 vs. 94 ml/min, 80.4 vs. 76 ml/min and 76.3 vs. 70 ml/min in respective age groups. Conclusion In the younger age group (20 to 40 years), there is better agreement in GFR measured by 99m Tc DTPA method and 24-hour urinary creatinine clearance methods.

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [99mTc][Tc(I)]+ core to obtain [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF were specific to bacteria. Compared with [99mTc]Tc-CN4NF, biodistribution studies of [99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.