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Click chemistry, in particular copper-free click reactions, has gained growing interest for radiolabelling purposes in the field of radiopharmaceutical sciences. [ 99m Tc][Tc(CO) 3 (H 2 O) 3 ] + works as an excellent starting complex for the radiolabelling of biomolecules under mild conditions. A new chelator, investigated for the copper-free strain-promoted cycloaddition (SPAAC), was synthesised containing the 2,2'-dipicolylamine (DPA) moiety for the 99m Tc-tricarbonyl core and compared with a DPA chelator based on activated esters for conventional radiolabelling. For the copper-free click labelling procedure, a DPA containing 4,8-diazacyclononyne moiety was prepared from a sulfonyl-modified diamide (four steps, 64% yield) followed by the Nicholas reaction with butyne-1,3-diol. The 99m Tc-DPA-DACN-complex was prepared with a radiochemical conversion (RCC) of 89% after 30 min. The following SPAAC reaction with an azide-functionalised PSMA molecule was performed within 4-5 hours at 100 °C to obtain the PSMA (prostate-specific membrane antigen) targeting 99m Tc-complex with 79% RCC and without side products. For comparison, a second DPA-chelator based on a tetrafluorophenyl (TFP) ester was prepared (three steps, 64% yield) and was successfully radiolabelled with [[ 99m Tc]Tc(CO) 3 (H 2 O) 3 ] + with 89% RCC after 20 min and >99% radiochemical purity after separation using an RP18 cartridge. The subsequent conjugation of an amine-functionalised PSMA targeting molecule was performed with 23% RCC after 150 min. Two other unknown side products were observed indicating the decomposition of the TFP ester during the labelling. All nonradioactive Re(CO) 3 complexes were synthesised from (Et 4 N) 2 [ReBr 3 (CO) 3 ] (91% yield for the nat Re-DPA-TFP ester, 76% yield for nat Re-DPA-DACN) and characterised to confirm the identity of the 99m Tc-complexes.

Three nitroimidazole propylene amine oxime (PnAO) derivatives with different lengths of ethylene glycol chain were synthesized and radiolabeled with 99m Tc. The radiochemical purities of three 99m Tc-labeled complexes, oxo[[6,6,12,12-tetramethyl-1,17-bis(2-nitro-1H-imidazol-1-yl)-3,15-dioxa-7,11-diazaheptadecane-5, 13-dione dioximato] (3-)-N,N',N'',N''']-technetium-99m ( 99m Tc-2P2O1), oxo[[9,9,15,15-tetramethyl-1,23-bis(2-nitro-1H-imidazol-1-yl)-3,6,18,21-tetraoxa-10, 14-diazatricosane-8,16-dione dioximato] (3-)-N,N',N'',N''']-technetium-99m ( 99m Tc-2P2O2) and oxo[[15,15,21,21-tetramethyl-1,35-bis(2-nitro-1H-imidazol-1-yl)-3,6,9,12,24,27,30,33-octaoxa-16,20-diazapentatriacontane-14,22-dione dioximato] (3-)-N,N',N'',N''']-technetium-99m ( 99m Tc-2P2O4), were above 90%, and they were all stable both in vitro and in vivo. The hypoxia/normoxia uptake ratios of the three complexes were 2.92 ± 0.61, 2.63 ± 0.64 and 2.29 ± 0.67 in S180 cellular uptake assay (4 h). All of these complexes presented good hypoxia selectivity. The results of biodistribution studies in S180 tumor-bearing mice revealed that the tumor/muscle (T/M) ratios (7.20 ± 2.37, 7.19 ± 1.75, 5.56 ± 1.10) and tumor/blood (T/B) ratios (1.66 ± 0.34, 1.73 ± 0.25, 2.13 ± 0.19) at 4 h of three complexes were significantly higher than those of 99m Tc-2P2 (3.24 ± 0.65, 0.81 ± 0.34) without the ethylene glycol chains. Among them, 99m Tc-2P2O4 had the best T/B ratio. The new complexes have higher tumor/blood and tumor/muscle ratios by adding suitable length of ethylene glycol chain. It is helpful for the design and optimization of hypoxic imaging agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L (+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO) 5 and fac -[NEt 4 ] 2 [ReBr 3 (CO) 3 ] were used for the preparation of the Re complexes fac -[Re(NNO)(CO) 3 ] ( 5a ) and fac -[Re(SNO)(CO) 3 ] ( 7a ) which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the fac -[ 99m Tc(CO) 3 ] + core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the fac -[ 99m Tc][Tc(OH 2 ) 3 (CO) 3 ] + precursor. The radiolabeled complexes were characterized by comparative HPLC analysis with the analogous rhenium (Re) complexes as references. In vitro studies in the A431 cell lines showed that both ligands and Re complexes inhibit A431 cell growth. Complex 5a demonstrated the highest potency (IC 50 = 8.85 ± 2.62 μM) and was further assessed for its capacity to inhibit EGFR autophosphorylation, presenting an IC 50 value of 26.11 nM. Biodistribution studies of the 99m Tc complexes in healthy mice showed high in vivo stability for both complexes and fast blood and soft tissue clearance with excretion occurring via the hepatobiliary system.

99 Tc is one of the predominant fission products of 235 U and an important component of nuclear industry wastes. The long half-life and specific activity of 99 Tc (212,000 y, 0.63 GBq g -1 ) makes Tc a hazardous material. Two principal ways were proposed for its disposal, namely, long-term storage and transmutation. Conversion to metal-like technetium matrices is highly desirable for both cases and for the second one the reasonably high Tc purity was important too. Tetramethylammonium pertechnetate (TMAP) was proposed here as a prospective precursor for matrix manufacture. It provided with very high decontamination factors from actinides (that is imperative for transmutation) by means of recrystallisation and it was based on the precise data on TMAP solubility and thermodynamics accomplished in the temperature range of 3-68 °C. The structure of solid pertechnetates were re-estimated with precise X-ray structure solution and compared to its Re and Cl analogues and tetrabutylammonium analogue as well. Differential thermal and evolved gas analysis in a flow of Ar-5% H 2 gas mixture showed that the major products of thermolysis were pure metallic technetium in solid matrix, trimethylammonium, carbon dioxide, and water in gas phase. High decontamination factors have been achieved when TMAP was used as an intermediate precursor for Tc.

With the objective to develop a potential 99m Tc radiopharmaceutical for imaging the androgen receptor (AR) in prostate cancer, four ligands bearing the same pharmacophore derived from the AR antagonist flutamide were prepared, labeled with 99m Tc, and their structures corroborated via comparison with the corresponding stable rhenium analogs. All complexes were obtained with high radiochemical purity. Three of the complexes were highly stable, and, due to their favorable physicochemical properties, were further evaluated using AR-positive and AR-negative cells in culture. All complexes exhibited considerable uptake in AR-positive cells, which could be blocked by an excess of flutamide. The efflux from the cells was moderate. They also showed significantly lower uptakes in AR-negative cells, indicating interactions with the AR receptor. However, the binding affinities were considerably reduced by the coordination to 99m Tc, and the complex that exhibited the best biological behavior did not show sufficient specificity towards AR-positive cells.

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) checkpoint blockade is a major breakthrough in cancer therapy, but identifying patients likely to benefit from this therapy remains challenging. Immunohistochemistry is not informative about PD-L1 expression heterogeneity because of the limitations of invasive tissue collection. Noninvasive SPECT imaging is an approach to patient selection and therapeutic monitoring by assessing the PD-L1 status throughout the whole body. Here, we radiolabeled a single-domain PD-L1 antibody with technetium-99m ( 99m Tc) for immune-SPECT imaging to evaluate its feasibility of detecting PD-L1 expression. The radiochemical purity of [ 99m Tc]Tc-HYNIC-KN035 was 99.40 ± 0.11% with a specific activity of 2.68 MBq/μg. [ 99m Tc]Tc-HYNIC-KN035 displayed a high PD-L1 specificity both in vitro and in vivo and showed a high specific affinity for PD-L1 with an equilibrium dissociation constant ( K D ) of 31.04 nM. The binding of [ 99m Tc]Tc-HYNIC-KN035 to H1975 cells (high expression of PD-L1) was much higher than to A549 cells (low expression of PD-L1). SPECT/CT imaging showed that H1975 tumors were visualized at 4 h post-injection and became clearer with time. However, mild tumor uptake was observed in A549 tumors and H1975 tumors of the blocking group at all time points. The uptake value of [ 99m Tc]Tc-HYNIC-KN035 in H1975 tumors was increased continuously from 9.68 ± 0.91% ID/g at 4 h to 13.31 ± 2.23% ID/g at 24 h post-injection, which was higher than in A549 tumors with %ID/g of 4.59 ± 0.76 and 5.54 ± 0.28 at 4 and 24 h post-injection, respectively. These specific bindings were confirmed by blocking studies. [ 99m Tc]Tc-HYNIC-KN035 can be synthesized easily and specifically targeted to PD-L1 in the tumor environment, allowing PD-L1 expression assessment noninvasively and dynamically with SPECT/CT imaging.

Background: 5-azacitidine is a very potent chemotherapeutic agent that suffers from certain disadvantages., Objective: This study aims to prepare gold nanoparticles as a new nano-formula of 5-azacitidine that can improve its bioavailability and decrease its side effects., Methods: 5-azacytidine-loaded GA-AuNPs were prepared and characterized by UV-Vis spectroscopy, infrared (IR), and electronic transmission microscope (TEM). This new platform was characterized in vitro by measuring its zeta potential, particle size, and drug loading efficacy, and the anti-proliferative effect on the MCF-7 cell line was evaluated. In vivo biodistribution studies of 99m Tc-5-aza solution and 99m Tc-5-aza-gold nano formula were conducted in tumor-bearing mice by different routes of administration (intravenous and intra-tumor)., Results: 5-Aza-GA-AuNPs formula was successfully prepared with an optimum particle size of ≈34.66 nm, the zeta potential of -14.4 mV, and high entrapment efficiency. 99m Tc-5-Aza-GA-AuNPs were successfully radiosynthesized with a labeling yield of 95.4%. Biodistribution studies showed high selective accumulation in tumor and low uptake in non-target organs in the case of the 5-Aza-GA-AuNPs formula than the 99m Tc-5-azacitidine solution., Conclusion: 99m Tc-5-Aza-GA-AuNPs improved the selectivity and uptake of 5-azacitidine in cancer. Moreover, 99m Tc-5-Aza-GA-AuNPs could be used as hopeful theranostic radiopharmaceutical preparation for cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Antimicrobial peptides (AMPs), due to their biological properties, have great potential for radiopharmaceutical development. In this research, a new antimicrobial peptide, derived from a 21-residue antimicrobial peptide microcinJ25 (MccJ25), was utilized to diagnose inflamed sites in mice bodies after labeling with [ 99m Tc]Tc., Materials and Methods: An antimicrobial peptide derivative was connected with an efficient chelator, hydrazinonicotinamide, and then labeled with [ 99m Tc]Tc. The binding of labeled microcinJ25 conjugate to lymphocyte was investigated in vitro. Turpentine oil-induced inflammation uptake and tissue distribution were assessed through the animal pattern. Detector scanning was done through scintigraphy post injection of [ 99m Tc]Tc-radiopeptide within different time points., Results: High radiochemical purity (>98%) was obtained for [ 99m Tc]Tc-radiopeptide. Lymphocyte binding assessment showed specific cell binding. Binding Inhibition was observed when additional unlabeled conjugate was used. In in vivo biological distribution studies, the uptake for inflamed tissue was 1.52 ± 0.12%ID/g. The inflammation site was visualized by scintigraphy imaging at 1 up to 2 hours., Conclusion: Based on our results this new designed [ 99m Tc]Tc-radiopeptide was able to detect inflammation sites early and with high resolution, and could be considered a promising diagnostic candidate in inflammatory diseases.

Antimicrobial resistance is a major challenge in the field and threat to human life. Many patients are suffering from cancer, infection and other diseases simultaneously. Therefore, early detection of infection can lead to treatment of these patients with an appropriate antibiotic. Hence, the development of a specific imaging molecule can increase the speed of infection analysis and thereby application of proper antibiotic. The present work involves the optimization of labelling conditions for an antibiotic of cephalosporin family, cephradine with technetium-99m ( 99m Tc) and establishment of quality control tests. Labelling of cephradine was also determined by applying MALDI-TOF mass spectrometry. Evaluation of in vitro binding with S. aureus bacteria was carried out. Animal model was used to conduct in vivo binding studies. For this, infected animals were injected with the radiolabelled ligand and images were captured by Gamma camera, to observe target to non-target uptake of radiolabelled complex. Furthermore, we optimized various parameters to achieve best labelling efficacy and stability of cephradine. Our results show that cephradine can be used as potential infection imaging agent for advanced clinical care.

Organometallic approaches are of ongoing interest for the development of novel functional 99m Tc radiopharmaceuticals, while the basic organotechnetium chemistry seems frequently to be little explored. Thus, structural and reactivity studies with the long-lived isotope 99 Tc are of permanent interest as the foundation for further progress in the related radiopharmaceutical research with this artificial element. Particularly the knowledge about the organometallic chemistry of high-valent technetium compounds is scarcely developed. Here, phenylimido complexes of technetium(V) with different isocyanides are introduced. They have been synthesized by ligand-exchange procedures starting from [Tc(NPh)Cl 3 (PPh 3 ) 2 ]. Different reactivity patterns and products have been obtained depending on the steric and electronic properties of the individual ligands. This involves the formation of 1:1 and 1:2 exchange products of Tc(V) with the general formulae [Tc(NPh)Cl 3 (PPh 3 )(isocyanide)], cis - or trans -[Tc(NPh)Cl 3 (isocyanide) 2 ], but also the reduction in the metal and the formation of cationic technetium(I) complex of the formula [Tc(isocyanide) 6 ] + when p-fluorophenyl isocyanide is used. The products have been studied by single-crystal X-ray diffraction and spectroscopic methods, including IR and multinuclear NMR spectroscopy. DFT calculations on the different isocyanides allow the prediction of their reactivity towards electron-rich and electron-deficient metal centers by means of the empirical SADAP parameter, which has been derived from the potential energy surface of the electron density on their potentially coordinating carbon atoms.

In this work, O- and N-N-bridging complexes of technetium (V), previously known only for rhenium, were obtained for the first time. Tc(V) complexes with pyridazine (pyd), 1,2,4-triazole (trz), 3,5-dimethylpyrazole (dmpz) and pyrimidine (pyr) were obtained. In three complexes [{TcOCl 2 } 2 (μ-O)(μ-pyd) 2 ], [{TcOCl 2 } 2 (μ-O)(μ-trz) 2 ]·Htrz·Cl and [{TcO(dmpz) 4 }(μ-O)(TcOCl 4 )] two technetium atoms are linked by a Tc-O-Tc bond, and in the first two, Tc atoms are additionally linked by a Tc-N-N-Tc bond through the nitrogen atoms of the aromatic rings. We determined the role of nitrogen atom position in the aromatic ring and the presence of substituents on the formation of such complexes. For the first time, a reaction mechanism for the formation of such complexes was proposed. This article details the crystal structures of four new compounds. The work describes in detail the coordination of Tc atoms in the obtained structures and the regularities of the formation of crystal packings. The spectroscopic properties of the obtained compounds and their mother solutions were studied. The decomposition temperatures of the described complexes were determined. An assumption was made about the oligomerization of three-bridged complexes based on the results of mass spectrometry. Through the analysis of non-valent interactions in the structures, π-stacking, halogen-π and CH-π interactions were found. An analysis of the Hirshfeld surface for [{TcOCl 2 } 2 (μ-O)(μ-pyd) 2 ], [{TcOCl2}2(μ-O)(μ-trz) 2 ] and their rhenium analogues showed that the main contribution to the crystalline packing is made by interactions of the type Hal···H/H···Hal (45.4-48.9%), H···H (10.2-15.8%), and O···H/H···O (9.4-16.5%).

Epidermal growth factor receptors (EGFR) of tyrosine kinase (TK) have shown high expression levels in most cancers and are considered a promising target for cancer diagnosis and therapy. Expanding the investigation for novel targeted radiopharmaceuticals, an EGFR inhibitor such as 4-aminoquinazoline derivatives along with a radionuclide such as technetium-99m ( 99m Tc) could be ideal. Thus, we report herein the synthesis, characterization, and biological evaluation of new "4 + 1" mixed-ligand Re III - and 99m Tc III -complexes of the general formula [ 99m Tc][Tc(NS 3 )(CN-R)] bearing tris(2-mercaptoethyl)-amine (NS 3 ) as the tetradentate tripodal ligand and a series of isocyanide derivatives (CN-R) of tyrosine kinase inhibitor (3-bromophenyl)quinazoline-4,6-diamine as the monodentate ligand. The quinazoline isocyanide derivatives 4a-d were prepared in two steps and reacted with the [Re(NS 3 )PMe 2 Ph] precursor leading to the final complexes 5a-d in high yield. All compounds were characterized by elemental analysis, IR, and NMR spectroscopies. In vitro studies, for their potency to inhibit the cell growth, using intact A431 cells indicate that the quinazoline derivatives 4a-d and the Re complexes 5a-d significantly inhibit the A431 cell growth. In addition, the EGFR autophosphorylation study of complex 5b shows an IC 50 value in the nanomolar range. The corresponding "4 + 1" 99m Tc-complexes 6a-d were prepared by employing the [ 99m Tc]TcEDTA intermediate and the appropriate monodentate 4a-d in a two-step synthetic procedure with a radiochemical yield (RCY) from 63 to 77 % and a radiochemical purity (RCP) > 99 % after HPLC purification. Their structures have been established by HPLC comparative studies using the well-characterized Re-complexes 5a-d as reference. All 99m Tc-complexes remain stable for at least 6 h, and their logD 7.4 values confirmed their anticipated lipophilic character. Biodistribution studies in healthy Swiss albino mice of 99m Tc-complexes showed hepatobiliary excretion and initial fast blood clearance. Complex 6b was also tested in Albino SCID mice bearing A431 tumors and showed rapid tumor uptake at 5 min (2.80 % ID/g) with a moderate tumor/muscle ratio (2.06) at 4 h p.i. The results encourage further investigation for this type of 99m Tc-complexes as single-photon emission computed tomography (SPECT) radio agents for imaging tumors overexpressing EGFR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In order to develop 99m Tc-labeled complexes with bisphosphonate isocyanide as novel bone imaging agents, two bisphosphonate isocyanide derivatives (CNALN and CNPAM) were synthesized and radiolabeling was performed for preparing the corresponding [ 99m Tc]Tc(I) complexes. [ 99m Tc]Tc-CNALN and [ 99m Tc]Tc-CNPAM were obtained with high radiochemical purity and showed good in vitro stability. Both of them were hydrophilic and had high affinity to hydroxyapatite. The biodistribution studies in mice revealed [ 99m Tc]Tc-CNALN showed higher bone/background ratios at 60 min post-injection. In single photon emission computed tomography (SPECT) imaging study, [ 99m Tc]Tc-CNALN had an obvious accumulation in bone, suggesting it would be a promising bone-seeking agent., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The syntheses of non-oxido/non-nitrido bis(thiosemicarbazonato)technetium(V) complexes featuring a series of alkyl and ether substituents is presented. The bis(thiosemicarbazones) were radiolabelled with technetium-99m using an optimised one-pot synthesis from [ 99m Tc][TcO 4 ] - . Mass spectrometry and computational chemistry data suggested a distorted trigonal prismatic coordination environment for the bis(thiosemicarbazonato)technetium(V) complexes by way of a bis(thiosemicarbazone)technetium(V)-oxido intermediate complex. The lipophilicities of the complexes were estimated using distribution ratios and three of the new complexes were investigated in mice using kinetic planar imaging and ex vivo biodistribution experiments and were compared to [ 99m Tc][TcO 4 ] - . Modification of the technetium complexes with various lipophilic functional groups altered the biodistributions of the complexes in mice despite evidence suggesting limited stability of the complexes to biologically relevant conditions. The most hydrophilic complex had higher uptake in the kidneys compared to the most lipophilic, which had higher liver uptake, suggesting modification of the excretion pathways.

The commercial low-pressure column chromatographic 99 Mo/ 99m Tc generator represents a reliable source of onsite, ready-to-use 99m Tc for industrial applications. These generators use fission-produced 99 Mo of high specific activity, posing serious production challenges and raising proliferation concerns. Therefore, many concepts are aimed at using low-specific-activity (LSA) 99 Mo. Nonetheless, the main roadblock is the low sorption capacity of the used alumina (Al 2 O 3 ). This study investigates the feasibility of using commercial alumina incorporated with LSA 99 Mo to develop a useful 99 Mo/ 99m Tc generator for industrial radiotracer applications. First, the adsorption profiles of some commercial alumina sorbents for LSA 99 Mo were tested under different experimental conditions. Then, the potential materials to develop a 99 Mo/ 99m Tc generator were selected and evaluated regarding elution yield of 99m Tc and purity. Among the sorbents investigated in this study, mesoporous alumina (SA-517747) presented a unique sorption-elution profile. It demonstrated a high equilibrium and dynamic sorption capacity of 148 ± 8 and 108 ± 6 mg Mo/g. Furthermore, 99m Tc was eluted with high yield and adequate chemical, radiochemical, and radionuclidic purity. Therefore, this approach provides an efficient and cost-effective way to supply onsite 99m Tc for radiotracer applications independent of fission-produced 99 Mo technology.

Technetium ( 99 Tc) is a highly toxic radioactive nuclear wastewater contaminant. Real-time detection of 99 Tc is very difficult due to its difficult-to-complex nature. Herein, a novel three-dimensional ionic olefin-linked conjugated microporous polymer (TFPM-EP-Br) is constructed using tetrakis(4-aldehyde phenyl)methane (TFPM) as the central monomer. The unique cationic cavity and highly hydrophobic framework enable TFPM-EP-Br to act as a fluorescent sensor for TcO 4 - . The fluorophores of TFPM-EP-Br can be quenched due to electron transfer from TFPM-EP-Br to TcO 4 - and the formation of strongly nonfluorescent complexes. Meanwhile, the regular pore channels are beneficial for the fast mass transfer of TcO 4 - , resulting in an ultrafast response time (less than 2 s) with an ultralow detection limit (33.3 nM). In addition, the ultrahigh specific surface area enables TFPM-EP-Br to combine the ability to synergistically detect and remove radioactive 99 Tc. From this perspective, the novel conjugated microporous polymer has made a breakthrough in the detection and extraction of radioactive contaminants.

Introduction: Dysregulated activity of matrix metalloproteinases (MMPs) drives a variety of pathophysiological conditions. Non-invasive imaging of MMP activity in vivo promises diagnostic and prognostic value. However, current targeting strategies by small molecules are typically limited with respect to the bioavailability of the labeled MMP binders in vivo. To this end, we here introduce and compare three chemical modifications of a recently developed barbiturate-based radiotracer with respect to bioavailability and potential to image MMP activity in vivo., Methods: Barbiturate-based MMP inhibitors with an identical targeting unit but varying hydrophilicity were synthesized, labeled with technetium-99m, and evaluated in vitro and in vivo. Biodistribution and radiotracer elimination were determined in C57/BL6 mice by serial SPECT imaging. MMP activity was imaged in a MMP-positive subcutaneous xenograft model of human K1 papillary thyroid tumors. In vivo data were validated by scintillation counting, autoradiography, and MMP immunohistochemistry., Results: We prepared three new 99m Tc-labeled MMP inhibitors, bearing either a glycine ([ 99m Tc]MEA39), lysine ([ 99m Tc]MEA61), or the ligand HYNIC with the ionic co-ligand TPPTS ([ 99m Tc]MEA223) yielding gradually increasing hydrophilicity. [ 99m Tc]MEA39 and [ 99m Tc]MEA61 were rapidly eliminated via hepatobiliary pathways. In contrast, [ 99m Tc]MEA223 showed delayed in vivo clearance and primary renal elimination. In a thyroid tumor xenograft model, only [ 99m Tc]MEA223 exhibited a high tumor-to-blood ratio that could easily be delineated in SPECT images., Conclusion: Introduction of HYNIC/TPPTS into the barbiturate lead structure ([ 99m Tc]MEA223) results in delayed renal elimination and allows non-invasive MMP imaging with high signal-to-noise ratios in a papillary thyroid tumor xenograft model., (© 2021. The Author(s).)

99mTc-DI-DD3B6/22-80B3 (ThromboView®, hereafter abbreviated to 99mTc-DI-80B3 Fab′) is a radiolabelled humanised monoclonal Fab′ fragment with affinity and specificity for D-dimer domains of cross-linked fibrin. Detection of thromboembolic events has been demonstrated in canine models. The study objectives were evaluation of safety and characterisation of biodistribution, immunogenicity and pharmacokinetic profile of increasing doses of 99mTc-DI-80B3 Fab′ in subjects with acute lower-limb DVT. Twenty-six patients with acute lower limb DVT were enrolled. Of these, 21 received a single intravenous dose of 0.5 mg ( n = 6), 1.0 mg ( n = 9) or 2 mg ( n = 6) 99mTc-DI-80B3 Fab′. Blood and urine samples and gamma camera images were collected to 24 h after administration for pharmacokinetic and dosimetry analysis. Vital signs, electrocardiography, hematological and biochemical data and human anti-human antibody (HAHA) levels were monitored for up to 30 days following administration. Patients were assigned to either planar or single photon emission computed tomographic (SPECT) imaging of the thorax at 4 h following injection. Thirty-five adverse events were reported in 15 of the 21 subjects. Those deemed possibly related to administration of 99mTc-DI-80B3 Fab′ included mild hypertension, mild elevation of LD (lactate dehydrogenase) and moderate elevation of ALT (alanine transaminase). HAHA assays remained negative. Pharmacokinetics and organ dosimetry were comparable to prior normal volunteer data. Localisation of Thromboview® to sites of known thrombus was evident as early as 30 min post-injection. In subjects with acute DVT, 99mTc-DI-80B3 Fab′ was well tolerated with favourable characteristics for the detection of acute venous thrombosis. [ABSTRACT FROM AUTHOR]

The first technetium complexes containing anionic alkynido ligands in an end-on coordination mode have been prepared by using the nonprotic, cationic precursor mer , trans -[Tc(SMe 2 )(CO) 3 (PPh 3 ) 2 ] + . This cation acts as a functional analogue of the highly reactive 16-electron metallo Lewis acid {Tc(CO) 3 (PPh 3 ) 2 } + in reactions with alkynes, acetylides, and other organometallic reagents. Such reactions give a variety of organometallic technetium complexes in excellent yields and enable the preparation of [Tc(CH 3 )(CO) 3 (PPh 3 ) 2 ], [Tc(Ph)(CO) 3 (PPh 3 ) 2 ], [Tc(Cp)(CO) 2 (PPh 3 )], [Tc(═CCH 2 CH 2 CH 2 O)(CO) 3 (PPh 3 ) 2 ] + , [Tc(═CCH 2 CH 2 CH 2 CH 2 O)(CO) 3 (PPh 3 ) 2 ] + , [Tc(C≡C-H)(CO) 3 (PPh 3 ) 2 ], [Tc(C≡C-Ph)(CO) 3 (PPh 3 ) 2 ], [Tc(C≡C- t Bu)(CO) 3 (PPh 3 ) 2 ], [Tc(C≡C- n Bu)(CO) 3 (PPh 3 ) 2 ], [Tc(C≡C-SiMe 3 )(CO) 3 (PPh 3 ) 2 ], and [Tc{C≡C-C 6 H 3 (CF 3 ) 2 }(CO) 3 (PPh 3 ) 2 ]. The bonding situation in the alkynyl complexes is compared to that in corresponding alkyl- and arylnitrile and -isonitrile complexes. [Tc(N≡C-Ph)(CO) 3 (PPh 3 ) 2 ](BF 4 ), [Tc(C≡N-Ph)(CO) 3 (PPh 3 ) 2 ](BF 4 ), [Tc(N≡C- t Bu)(CO) 3 (PPh 3 ) 2 ](BF 4 ), and [Tc(C≡N- t Bu)(CO) 3 (PPh 3 ) 2 ](BF 4 ) were prepared in high yields by ligand exchange reactions starting from mer , trans -[Tc(OH 2 )(CO) 3 (PPh 3 ) 2 ](BF 4 ). The novel complexes were characterized by single-crystal X-ray diffraction and spectroscopic methods. In particular, 99 Tc nuclear magnetic resonance spectroscopy proved to be an invaluable and sensitive tool for the characterization of the complexes. Density functional theory calculations strongly suggest similar bonding situations for the related alkynyl, nitrile, and isonitrile complexes of technetium.

In this study, 99m Tc-plazomicin, a new radio-antibiotic complex, was prepared specifically for bacterial infection localization and monitoring. Factors affecting the labeling reaction were studied and optimized to obtain a high yield (98.8 ± 0.2%). In silico, radiochemical and physicochemical characterization and biodistribution were performed to assess the complex aptness as a radiopharmaceutical. The complex was biologically evaluated in vitro using bacteria and in vivo using different inflammation models (sterile, bacterial, and fungal). Uptake in the bacterial model was highest (7.8 ± 0.3%). Results indicated that the technetium label did not alter the antibiotic biological behavior and backed the usefulness of 99m Tc-plazomicin as a potential tracer., (© 2021 John Wiley & Sons A/S.)

Introduction: With the goal of developing theranostic agents for application in radiopharmaceutical chemistry, in this work, we studied p-NCS-Bn-NODAGA (1) as a bifunctional chelator for the fac-[M(CO) 3 ] + core (M = nat Re, 186 Re, 99m Tc). Specifically, we studied complexes of the formula [M(CO) 3 (L)] + , where L denotes either Bn-NODAGA-Pyr (2) or Bn-NODAGA-Ser-Ser-RM2 (3)., Methods: The model bioconjugate molecule 2 was synthesized by conjugating pyrrolidine with 1, while 3 was derived from the conjugation of the gastrin-releasing peptide receptor (GRPR)-targeting peptide Ser-Ser-RM2 with 1. Labeling of 2 and 3 was performed with [M(CO) 3 (OH 2 ) 3 ] + (where M = nat Re, 186 Re, or 99m Tc). The stability of the radioactive complexes was studied against l-histidine and l-cysteine (1 mM in PBS; pH 7.4, 37 °C). GRPR affinity of both peptide 3 and its metallated counterpart, Re-3, were determined with in vitro competitive binding assays in GRPR-expressing PC-3 cells using [ 125 I]I-Tyr 4 -BBN as the competitor., Results: After a thorough radiolabeling optimization process, the [M(CO) 3 (2)] + model complexes (M = 186 Re and 99m Tc) were synthesized with 94 ± 2% radiochemical yield (RCY; estimated by radio-HPLC). In stability studies, [ 186 Re]Re-2 remained intact through 7 d in l-cysteine and l-histidine. Similarly, stability studies in rat serum at 37 °C showed 99 ± 1% intact [ 186 Re]Re-2 through 4 h. Non-specific rat serum protein binding of [ 186 Re]Re-2 was found to be 33 ± 4% at 4 h. The [ 99m Tc]Tc-2 complex was found to be stable in l-histidine and l-cysteine at 37 °C through 24 h. [ 99m Tc]Tc-2 was also stable in rat serum, with 38 ± 3% non-specific protein binding, at 4 h. The [M(CO) 3 (3)] + peptide radiometal complex (M = 186 Re and 99m Tc) syntheses were also optimized, resulting in RCYs of 35% for [ 186 Re]Re-3 and 47% for [ 99m Tc]Tc-3 (estimated by radio-HPLC). [ 186 Re]Re-3 showed 98 ± 2% and 84 ± 5% stability in l-histidine and l-cysteine, respectively, through 48 h. Similarly, stability studies in rat serum at 37 °C showed 85 ± 3% intact [ 186 Re]Re-3 through 4 h, with 29 ± 7% non-specific protein binding in rat serum. [ 99m Tc]Tc-3 was found to be 84 ± 3% and 82 ± 4% stable in l-histidine and l-cysteine at 24 h, respectively. [ 99m Tc]Tc-3 in rat serum at 37 °C showed 88 ± 2% stability through 4 h, with 25 ± 2% non-specific protein binding. Both 3 and Re-3 demonstrated high GRPR affinity, with IC 50 values of 3.1 nM and 3.9 nM, respectively., Conclusions: The low nanomolar IC 50 values obtained for 3 and Re-3 demonstrate high affinity of this novel [M(CO) 3 ]-labeled bioconjugate for GRPR. The encouraging stability studies and receptor affinity results demonstrate promise for further development of these metal complexes as a theranostic matched pair for targeting GRPR., (Copyright © 2022 Elsevier Inc. All rights reserved.)

PURPOSE The aim of the study was to radiolabel, characterize, and perform in vitro and in vivo assessment of Technetium-99m (Tc-99m) tamoxifen for screening ER expressing lesions in breast cancer patients. METHODS In this study, tamoxifen has been radiolabeled with Tc-99m via Tc-99m-tricarbonyl core. The characterization and quality control tests of Tc-99m-tamoxifen were performed. In vitro recep- tor binding and blocking studies were performed in both positive control (MCF-7) and negative control cell lines (MDA-MB-231). Normal biodistribution studies were performed in female Wistar albino rats. The pilot clinical studies were performed in 4 ER-expressing breast cancer patients. Of the 4 patients, 1 was on tamoxifen therapy. All 4 patients had also undergone Fluorine-18 fluorodeoxyglucose (F-18-FDG) positron emission tomography/computed tomography. RESULTS Tamoxifen was radiolabeled with Tc-99m via Tc-99m-tricarbonyl core with more than 95% radio- chemical yield. Mass spectra showed a peak corresponding to the molecular weight of Tc-99m- tricarbonyl and Tc-99m-tamoxifen. The site of binding of Tc-99m-tricarbonyl with tamoxifen was determined by proton nuclear magnetic resonance. The Tc-99m-tamoxifen showed 30% binding with MCF-7 and only 1%-2% receptor binding with MDA-MB-231 cell lines. Also, the percentage of receptor binding was drastically reduced (up to 72%) when ER was saturated with 50 times the excess molar ratio of unlabeled tamoxifen. In a pilot patient study, Tc-99m-tamoxifen uptake was observed in primary and metastatic lesions. However, no uptake was observed in a patient who was on tamoxifen therapy. The uptake of F-18-FDG was noted in all the patients. CONCLUSION Tamoxifen was radiolabeled with an in-house-synthesized Tc-99m-tricarbonyl core. The radio- labeled complex has been characterized and evaluated for receptor specificity in in vitro and in vivo studies. Also, this is the first clinical study using Tc-99m-tamoxifen for imaging ER. More patients need to be evaluated to further explore the role of Tc-99m-tamoxifen in ER-expressing lesions.

Dopamine is one of the most important neurotransmitters released by neurons in the central nervous system, and a variety of neurological illnesses and mental disorders are associated with impairments in the secretion and functionality of dopamine. Dopamine, depending on the type of receptors, can act as a stimulant or an inhibitor. In this study, dendrimer-conjugated dopamine was utilized as a chelating agent for Technetium-99m to investigate the organ distribution of this compound in vivo using the single-photon emission computed tomography (SPECT) technique. For this purpose, dendrimers were synthesized using polyethylene glycol diacid and citric acid precursors, and dopamine was conjugated to the dendrimer using EDC/NHS cross-linker. The results showed no sign of toxicity of the dopamine-functionalized dendrimers on HEK-293 cell lines. The optimization of labeling conditions was conducted using the experimental design method (i.e., conjugate value, pH, and the amount of reducing agent), and then labeling efficiency was evaluated by thin-layer chromatography (TLC). Finally, the study of organ distribution in normal mice using SPECT imaging and comparing it with gene expression in different organs revealed that dopamine D1 receptors exhibited the highest accumulation in the liver and that the drug retained its specificity.

Background : The [ 99m Tc][Tc(N)(PNP)] system, where PNP is a bisphosphinoamine, is an interesting platform for the development of tumor ' receptor-specific ' agents. Here, we compared the reactivity and impact of three [Tc(N)(PNP)] frameworks on the stability, receptor targeting properties, biodistribution, and metabolism of the corresponding [ 99m Tc][Tc(N)(PNP)]-tagged cRGDfK peptide to determine the best performing agent and to select the framework useful for the preparation of [ 99m Tc][Tc(N)(PNP)]-housing molecular targeting agents. Methods: cRGDfK pentapeptide was conjugated to Cys and labeled with each [Tc(N)(PNP)] framework. Radioconjugates were assessed for their lipophilicity, stability, in vitro and in vivo targeting properties, and performance. Results: All compounds were equally synthetically accessible and easy to purify (RCY ≥ 95%). The main influences of the synthon on the targeting peptide were observed in in vitro cell binding and in vivo. Conclusions: The variation in the substituents on the phosphorus atoms of the PNP enables a fine tuning of the biological features of the radioconjugates. ws [ 99m Tc][Tc(N)(PNP3OH)]- and [ 99m Tc][Tc(N)(PNP3)]- are better performing synthons in terms of labeling efficiency and in vivo performance than the [ 99m Tc][Tc(N)(PNP43)] framework and are therefore more suitable for further radiopharmaceutical purposes. Furthermore, the good labeling properties of the ws [ 99m Tc][Tc(N)(PNP3OH)]- framework can be exploited to extend this technology to the labeling of temperature-sensitive biomolecules suitable for SPECT imaging.

Objective: Pep-1 (CGEMGWVRC) can potently bind to interleukin 13 receptor α 2 (IL-13Rα2), a tumor-restricted receptor found to be expressed in various malignancies. In this study, we intended to prepare a 99m Tc-labeled probe and evaluate its in vivo tumor accumulation properties in a cervical cancer xenograft model., Methods: The Pep-1 was designed and radiolabeled with 99m Tc by conjugation with mercaptoacetyl-triglycine (MAG 3 ). The labeling yield, radiochemical purity and stability were characterized in vitro. Cell uptake assays and fluorescence imaging were conducted for qualitative and quantitative evaluation of the specificity and affinity of Pep-1. Flow cytometry and tissue immunofluorescence were used to confirm the IL-13Rα2 expression in cervical cancer. Biodistribution and in vivo imaging were performed periodically to evaluate the imaging value of 99m Tc-MAG 3 -Pep-1 in cervical cancer xenograft model., Results: 99m Tc-MAG 3 -Pep-1 was successfully prepared with a high labeling yield and radiochemical purity (> 95%). Specific cell uptake was demonstrated by scramble control and unlabeled MAG 3 -Pep-1 blockade. Flow cytometry and tissue immunofluorescence also confirmed the mild IL-13Rα2 expression of HeLa. In the gamma imaging study and biodistribution, the tumors were imaged clearly at 2-6 h after injection of 99m Tc-MAG 3 -Pep-1 and the accumulation of 99m Tc-MAG 3 -Pep-1 in tumor was significantly higher than that in the blocking and scramble controls, demonstrating ligand-receptor binding specificity., Conclusions: This work demonstrated that 99m Tc-MAG 3 -Pep-1 can bind to cervical cancer with high affinity and specificity. MAG 3 -Pep-1 may be a prospective precursor for IL-13Rα2-expressing cancer therapy., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

The incorporation of bioactive molecules into a water-soluble [ 99m Tc][Tc(N)(PNP)]-based mixed compound is described. The method, which exploits the chemical properties of the new [ 99m Tc][Tc(N)(PNP3OH)] 2+ synthon [PNP3OH = N , N -bis(di-hydroxymethylenphosphinoethyl)methoxyethylamine], was successfully applied to the labeling of small, medium (cysteine-functionalized biotin and c-RGDfK pentapeptide), and large molecules. Apomyoglobin was chosen as a model protein and derivatized via site-specific enzymatic reaction catalyzed by transglutaminase (TGase) with the H-Cys-Gly-Lys-Gly-OH tetrapeptide for the insertion in the protein sequence of a reactive N-terminal Cys for 99m Tc chelation. Radiosyntheses were performed under physiological conditions at room temperature within 30 min. They were reproducible, highly specific, and quantitative. Heteroleptic complexes are hydrophilic and stable. Biodistributions of the selected compounds show favorable pharmacokinetics within 60 min post-injection and predominant elimination through the renal-urinary pathway. In a wider perspective, these data suggest a role of the [ 99m Tc][Tc(N)(PNP)] technology in the labeling of temperature-sensitive biomolecules, especially targeting proteins for SPECT imaging.

The epidermal growth factor receptor (EGFR) is over-expressed in various human cancer. The over-expression of EGFR in tumors is an excellent target for the development of cancer imaging agents. In the present study, we developed Tc-99m SYPIPDT-GHEG-ECG-K-tetramethylrhodamine (SYPIPDT-ECG-TAMRA) as a molecular imaging agent targeting wild-type EFGR (wtEGFR)-positive tumor cells, and verified its feasibility as molecular imaging agent. SYPIPDT-ECG-TAMRA was synthesized using Fmoc solid-phase peptide synthesis. The radiolabeling of SYPIPDT-ECG-TAMRA with Tc-99m was accomplished using ligand exchange via tartrate. Cellular uptake and binding affinity studies were performed. In vivo gamma camera imaging, ex vivo imaging and biodistribution studies were performed using NCI-H460 and SW620 tumor-bearing murine models. After radiolabeling procedures with Tc-99m, Tc-99m SYPIPDT-ECG-TAMRA complexes were prepared at high yield (> 95%). The binding affinity value (Kd) of Tc-99m SYPIPDT-ECG-TAMRA for NCI-H460 cells was estimated to be 76.5 ± 15.8 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc-99m SYPIPDT-ECG-TAMRA increased with time (2.7 ± 0.6, 4.0 ± 0.9, and 6.2 ± 1.0 at 1, 2, and 3 h, respectively). The percentage injected dose per gram of wet tissue for the NCI-H460 tumor was 1.91 ± 0.11 and 1.70 ± 0.22 at 1 and 3 h, respectively. We developed Tc-99m SYPIPDT-ECG-TAMRA, which is dual-labeled with both radioisotope and fluorescence. In vivo and in vitro studies demonstrated specific uptake of Tc-99m SYPIPDT-ECG-TAMRA into wtEGFR-positive NCI-H460 cells and tumors. Thus, the results of the present study suggest that Tc-99m SYPIPDT-ECG-TAMRA is a potential dual-modality imaging agent targeting wtEGFR., Competing Interests: The authors have declared that no competing interests exist.

Background: Macroaggregated human serum albumin (MAA) properties are widely used in nuclear medicine, labelled with 99m Tc. The aim of this study is to improve the knowledge about the morphology, size, dimension and physical-chemical characteristics of MAA and their bond with 99m Tc and 68 Ga., Methods: Commercial kits of MAA (Pulmocis ® ) were used. Characterisation through experiments based on SEM, DLS and Stokes' Law were carried out. In vitro experiments for Langmuir isotherms and pH studies on radiolabelling were performed and the stability of the radiometal complex was verified through competition reactions., Results: The study settles the MAA dimension within the range 43-51 μm. The Langmuir isotherm reveals for [ 99m Tc]MAA: Bmax (46.32), h (2.36); for [ 68 Ga]MAA: Bmax (44.54), h (0.893). Dual labelling reveals that MAA does not discriminate different radioisotopes. Experiments on pH placed the optimal pH for labelling with 99m Tc at 6., Conclusion: Radiolabelling of MAA is possible with high efficiency. The nondiscriminatory MAA bonds make this drug suitable for radiolabelling with different radioisotopes or for dual labelling. This finding illustrates the need to continue investigating MAA chemical and physical characteristics to allow for secure labelling with different isotopes.

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

Discovery of penicillin marked a turning point in the history of infection therapy which also led to the emergence of bacterial resistance. It is now 100 years to fight with ever-muted variants of pathogens by developing more and more antibiotics. Since 1987 to todate, no successful class of antibiotic was introduced; this three decade period is known as "the discovery void" period. While, the clinically approved antibiotics are gradually dying in front of bacterial resistance due to which bacterial infections are appearing leading cause of death and disability. Nuclear medicine imaging technique is the strongest modality to diagnose and follow-up of deep-seated and complicated infections. However, the selection of radiolabeled antimicrobial agents plays critical role in gaining sensitivity and specificity of the imaging results. This review comprises of two main sections; first section explains antibiotic targets, and second section explains the imaging efficacy of 99m Tc-labeled antimicrobial agents against bacterial infection along with the emphasis on progress and update of 99m Tc-labeled antibiotics as infection imaging probes. The review, in conclusion, could be an acceleration for radiopharmaceutical chemists for designing and developing 99m Tc-labeled antimicrobial agents to improve infection imaging quality., (© 2021 John Wiley & Sons A/S.)

Introduction: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer (PCa). The aptamer (Apt) A10-3.2 can be used as a specific ligand for the early diagnosis and targeted treatment of PCa. siRNA-Apt has been used to therapeutically target PSMA-positive PCa. We aimed to synthesize a new type of molecular probe to facilitate the integration of diagnosis and treatment for PSMA-positive PCa., Methods: Chimeras were obtained by covalent linking PSMA Apt-A10-3.2 and the MDM2 siRNA. SHNH, a bifunctional chelating agent, was used to couple 99m Tc with chimeras to synthesize a new molecular probe. Labeling efficiency, radiochemical purity, and stability were confirmed using a γ-well counter and Whatman paper No.1. SPECT imaging and biodistribution studies were performed on BALB/c mice bearing 22Rv1 or PC-3 xenografts. Tumor inhibition and cytotoxicity of Chimeras were evaluated. LNCaP, 22RV1, and PC-3 PCa cell lines were used for in vitro and in vivo experiments., Results: [ 99m Tc]Tc-chimeras showed high labeling efficiency (61.47% ± 2.85%, n = 3), radiochemical purity (>95%), and stability. Biodistribution studies and SPECT imaging with 99m Tc-chimeras in mice bearing 22Rv1 xenografts demonstrated a high T/M ratio (4.63 ± 0.68, n = 3) and a high T/B ratio (3.61 ± 0.7, n = 3) at 2 h post-injection. 99m Tc-chimeras showed rapid renal clearance. Compared with the PBS group, tumor growth in the chimera group was significantly inhibited (P < 0.01, n = 4), but there was no significant difference in body weight (p > 0.05, n = 4). H&E staining showed no obvious liver or kidney damage., Conclusions: Our study proved that [ 99m Tc]Tc-Aptamer-siRNA chimeras could be used to diagnose and treat PSMA-positive PCa in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A novel proof-of-concept is reported to modify the water solubility and potential biological effects of a bis(diphenylphosphino)alkylamine (PNP) ligand and the corresponding metal complex, by introducing an amine group on the outer periphery of the pendant ligand arm. Thus, a tertiary butoxycarbonyl protected N '-Boc-ethylenediamine- N , N -bis(diphenylphosphino) ( N '-Boc-PNP) ligand (1) was synthesized by reacting the protected ethylenediamine and chlorodiphenylphosphine in a 1 : 2 molar ratio. The corresponding fac -[Re(CO) 3 ( N '-Boc-PNP)Br] (1A) complex was then obtained by reacting N '-Boc-PNP (1) with (Et 4 N) 2 fac -[Re(CO) 3 Br 3 ] in equimolar amounts in DCM at 50 °C. De-protection of the N '-Boc pendant amine group in 1A with TFA leads to fac -[Re(NH 3 + -PNP)(CO) 3 Br]·CF 3 COO - (1B) which is soluble in D 2 O (>0.05 M). Treating 1B with saturated aqueous NaHCO 3 yields fac -[Re(NH 2 -PNP)(CO) 3 Br]·MeOH (1C) in near quantitative yield. Although both 1A and 1C are not soluble in D 2 O, addition of TFA easily generates 1B ( 31 P NMR), confirming the formation of the protonated amine. Isolation of fac -[ 99 Tc(CO) 3 ( N -Boc-PNP)(Cl)] (1D) confirmed that the rhenium and technetium ( 99 Tc) can be easily interchanged in this process. Reported are hence the unique rhenium series of compounds 1A, 1B and 1C and the corresponding technetium complex 1D, unequivocally characterized by single crystal XRD, as well as IR and 1 H NMR spectroscopy. Preliminary antimicrobial evaluation indicates that ligand 1 and its respective rhenium complexes (1A-1C) were not active against selected fungi ( Candida albicans and Cryptococcus neoformans ) and bacteria ( Escherichia coli , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa and Staphylococcus aureus ). These types of ligands and complexes therefore present themselves as excellent radio models for further evaluation using 186 Re, 188 Re and 99m Tc to potentially study the radio toxicity of appropriately designed complexes.

The fac -[M(CO) 3 (PyA)(P)] and cis-trans -[M(CO) 2 (PyA)(P) 2 ] neutral complexes (M is Re or 99m Tc), based on the mixed ligand strategy with pyrazine-2-carboxylic acid (PyAH) as the bidentate N,O and triphenylphosphine as the monodentate P ligand, are presented. Through the employment of the anhydride of pyrazine-2,3-dicarboxylic acid (PyDA), the PyAH scaffold was conveniently derivatized with the model bioactive amine 1-(2-methoxyphenyl)piperazine, the active part of the 5-HT 1A antagonist WAY100635. Reaction of either PyAH or the pharmacophore-bearing PyAH ligand (L 1 H) with fac- [M(CO) 3 ] + core in water yielded the intermediate fac -[M(CO) 3 (PyA)(H 2 O)] complexes. The labile aqua ligand was easily replaced by PPh 3 to yield the fac -[Re(CO) 3 (PyA)(PPh 3 )] complexes, while in toluene under reflux, the cis-trans -[Re(CO) 2 (PyA)(PPh 3 ) 2 ] complexes were obtained. The latter complexes were alternatively obtained from mer -[Re(CO) 3 (PPh 3 ) 2 Cl] by refluxing with the PyA ligand in toluene. The analogous 99m Tc complexes were synthesized quantitatively, showing excellent stability in competition studies. The methodology described herein represents a practical procedure for the effective integration of the fac -[M(CO) 3 ] + core with amine-bearing biologically active compounds for diagnosis/therapy.

Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether 99m Tc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the 99m Tc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of 99m Tc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5's recognition/specificity ability were observed after the radiolabeling. The GA-5's radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.

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

Early and sensitive diagnosis of pancreatic diseases is a contemporary clinical challenge. Zinc level in pancreatic tissue and its secretion in pancreatic juice has long been considered a surrogate marker of pancreatic function. The objective of this study was to design a Zn-chelating imaging probe (ZCIP) which could be labeled with 99m Tc radionuclide for imaging of pancreas using single photon emission tomography (SPECT). We synthesized ZCIP as a bifunctional chelate consisting of diethylene triamine pentaacetic acid for 99m Tc-chelation at one end and bispicolylethylamine for Zn-complexation at the other end. ZCIP was labeled with 99m Tc by standard Sn 2+ -based reduction method. The 99m Tc-labeled ZCIP was studied in normal mice (0.3 mCi) for SPECT imaging. We found that ZCIP consistently labeled with 99m Tc radionuclide with over 95% efficiency. Addition of ZCIP altered the spectrum of standard dithizone-Zn complex, indicating its ability to chelate Zn. SPECT data demonstrated the ability of 99m Tc-ZCIP to image pancreas with high sensitivity in a non-invasive manner; liver and spleen were the other major organs of 99m Tc-ZCIP uptake. Based on these results, we conclude that 99m Tc-ZCIP presents as a novel radiotracer for pancreas imaging for diagnosis of diseases such as pancreatitis., (Copyright © 2021. Published by Elsevier Ltd.)

Chemotherapy is a standard therapeutic option for triple-negative breast cancer (TNBC); however, its effectiveness is often compromised by drug-related toxicity and resistance development. Herein, we aimed to evaluate whether an improved antineoplastic effect could be achieved in vitro and in vivo in TNBC by combining dovitinib, a multi-kinase inhibitor, with calcitriol, a natural anticancer hormone. In vitro, cell proliferation and cell-cycle distribution were studied by sulforhodamine B-assays and flow cytometry. In vivo, dovitinib/calcitriol effects on tumor growth, angiogenesis, and endothelium activation were evaluated in xenografted mice by caliper measures, Itgb3/VEGFR2-immunohistochemistry and 99m Tc-Ethylenediamine-N,N-diacetic acid/hydrazinonicotinamyl-Glu[cyclo(Arg-Gly-Asp-D-Phe-Lys)] 2 ( 99m Tc-RGD 2 )-tumor uptake. The drug combination elicited a synergistically improved antiproliferative effect in TNBC-derived cells, which allowed a 7-fold and a 3.3-fold dovitinib dose-reduction in MBCDF-Tum and HCC-1806 cells, respectively. Mechanistically, the co-treatment induced a cell cycle profile suggestive of cell death and DNA damage (accumulation of cells in SubG1, S, and G2/M phases), increased the number of multinucleated cells and inhibited tumor growth to a greater extent than each compound alone. Tumor uptake of 99m Tc-RGD 2 was reduced by dovitinib, suggesting angiogenesis inhibition, which was corroborated by decreased endothelial cell growth, tumor-vessel density and VEGFR2 expression. In summary, calcitriol synergized dovitinib anticancer effects in vitro and in vivo, allowing for a significant dose-reduction of dovitinib while maintaining its antiproliferative potency. Our results suggest the beneficial convergence of independent antitumor mechanisms of dovitinib and calcitriol to inhibit TNBC-tumor growth., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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

The radiochemical purity (RCP) determination of radiopharmaceuticals is routinely done with radio-thin layer chromatography (r-TLC). These methods are usually transposed and adjusted from the summary product characteristics without any analytical validation. The r-TLC method is simple but manually-performed steps could lead to RCP misinterpretation. To increase the sensitivity, radio ultra-high performance liquid chromatography (r-UHPLC) can be used. In this study, an r-UHPLC method had been validated and compared to the r-TLC method. Hydrolyzed-reduced technetium had also been studied., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Sphingosine-1-phosphate (S1P) is a phospholipid that regulates pleiotropic biological activities and exerts extracellular functions by binding to five specific G-protein-coupled receptors, S1P receptors (S1PR) 1-5. When activated by S1P, S1PR promote the proliferation and invasion of tumor cells by inducing the formation of new blood vessels. We developed and assessed a new monoclonal antibody imaging probe 99m Tc-HYNIC-S1PR1mAb, to explore the feasibility of targeting the S1PR1 in vitro and in vivo . S1PR1mAb was prepared and followed by technetium-99m labeling with succinimidyl 6-hydraziniumnicotinate hydrochloride. Cell uptake and blocking studies were performed to investigate the binding specificity of 99m Tc-HYNIC-S1PR1mAb in vitro . 99m Tc-HYNIC-S1P1mAb was also tested in vivo in mice xenografted with SK-HEP-1 (high-expression of S1PR1) and MCF-7 (low-expression of S1PR1) using single-photon emission-computed tomography (SPECT). Ex vivo gamma counting of tissues from tumor-bearing mice was used to evaluate 99m Tc-HYNIC-S1PR1mAb biodistribution. The biodistribution study results showed significantly higher uptake in SK-HEP-1 tumors than in MCF-7 tumors (P < 0.001). Reduced uptake of 99m Tc-HYNIC-S1PR1mAb in SK-HEP-1 was observed in tumor-bearing nude mice pretreated with fingolimod, which binds competitively to the receptors, especially S1PR1. 99m Tc-HYNIC-S1PR1mAb can be synthesized and specifically targeted to S1PR1 in vitro and in vivo , allowing S1PR1 expression assessment with SPECT imaging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ye, Gai, Ji, Jiang, Qiao, Wang, Zhang, Xia and Lan.)

Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to 99m Tc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of lymph node macrophages. The current study aimed to synthesize, characterize, and biologically evaluate a series of mannosylated dextran derivatives labeled with 99m Tc for potential use in SLND. The compounds were designed to have a dextran with a molecular weight of 10-500 kDa as a backbone, S-derivatized cysteines, efficient SNO chelators, and mannose moieties for binding to mannose receptors. They were successfully synthesized, thoroughly characterized using NMR techniques, and labeled with the fac -[ 99m Tc(CO) 3 ] + synthon. Labeling with high yields and radiochemical purities was achieved with all derivatives. In vivo biodistribution and imaging studies demonstrated high uptake in the first lymph node and low uptakes in the following node and confirmed the ability to visualize the SLN. Among the compounds studied, 99m Tc-D75CM demonstrated the most attractive biological features, and in combination with the high radiochemical yield and stability of the compound, its further evaluation as a new radiopharmaceutical for sentinel lymph node detection was justified.

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [ 99m Tc]Tc-CN5FA and [ 99m Tc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [ 99m Tc]Tc-CN5FA and [ 99m Tc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [ 99m Tc]Tc-CN5FA and [ 99m Tc]Tc-CNPFA had specific tumor uptake. Compared with [ 99m Tc]Tc-CN5FA, the tumor/muscle ratios of [ 99m Tc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two 99m Tc complexes have potential as tumor imaging agents to target folate receptors.

Quantitative changes in expression level of 5HT 1A are somewhere related to common neurological disorders such as anxiety, major depression and schizophrenia. We have designed EDTA conjugated SPECT imaging probe for localization of 5HT 1A receptor in brain. For designing SPECT probe we have employed the concept of bivalent approach and a homodimeric system with desirable pharmacokinetics of 5HT 1A imaging. 99m Tc-EDHT was also evaluated for its stability through serum stability assay and glutathione challenge experiment. Biodistribution study showed the highest accumulation of radioactivity in kidney which depicted the renal mode of excretion from the body. However in brain the uptake of 1.21% ID per gram was observed in initial 5 min of drug administration. On blocking the receptor this percent get decreased to 0.97% ID per gram. The regional distribution in brain was also performed which showed the accumulation of drug in cerebellum, cortex and hippocampus part, which are already known for 5HT 1A expression. Dynamic study in rabbit is also in support of results derived from biodistribution and blood kinetics experiment. These finding suggest that 99m Tc-EDHT holds promising place for further optimization before nuclear medicine applications in different animal species., (Copyright © 2021. Published by Elsevier Inc.)

The zinc dithiocarbamates functionalized with folic acid 2 Zn and 3 Zn were synthesized with a simple straightforward method, using an appropriated folic acid derivative and a functionalized zinc dithiocarbamate ( 1 Zn ). Zinc complexes 2 Zn and 3 Zn show very low solubilities in water, making them useful for preparing Tc-99m radiopharmaceuticals with a potentially high molar activity. Thus, the transmetallation reaction in water medium between the zinc complexes 2 Zn or 3 Zn and the cation fac -[ 99m Tc(H 2 O) 3 (CO) 3 ] + , in the presence of the monodentate ligand TPPTS, leads to the formation of the 2 + 1 complexes fac -[ 99m Tc(CO) 3 (SS)(P)] bioconjugated to folic acid ( 2 Tc and 3 Tc ). In spite of the low solubility of 2 Zn and 3 Zn in water, the reaction yield is higher than 95%, and the excess zinc reagent is easily removed by centrifugation. The Tc-99m complexes were characterized by comparing their HPLC with those of the homologous rhenium complexes ( 2 Re and 3 Re ) previously synthesized and characterized by standard methods. Preliminary in vivo studies with 2 Tc and 3 Tc indicate low specific binding to folate receptors. In summary, Tc-99m folates 2 Tc and 3 Tc were prepared in high yields, using a one-pot transmetallation reaction with low soluble zinc dithiocarbamates (>1 ppm), at moderate temperature, without needing a subsequent purification step.

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

γ-Tilmanocept ( 99m Tc-tilmanocept) is a receptor-directed, radiolabeled tracer that is FDA-approved for guiding sentinel lymph node biopsy. Tilmanocept binds the C-type lectin mannose receptor (MR, CD206) on macrophages. In this study, nonradioactive, fluorescently-labeled Cy3-tilmanocept was used to detect CD206 + mononuclear cells in the cartilage of mice with antibody-induced arthritis and in the synovial fluid and tissue of human subjects with rheumatoid arthritis (RA) for comparison with osteoarthritis (OA), and healthy volunteer (HV) controls. Murine arthritis was induced by injection of monoclonal anti-cartilage antibody followed by injection of Escherichia coli lipopolysaccharide. Post-arthritis development (7-11 days), the mice were injected intravenously with Cy3-tilmanocept followed by in vivo and ex vivo epifluorescence imaging. Two-photon imaging, immunofluorescence, and immunohistochemistry were used to identify articular and synovial macrophages (CD206, F4/80, and Cy3-tilmanocept binding) in murine tissues. Cy3-tilmanocept epifluorescence was present in arthritic knees and elbows of murine tissues; no radiographic changes were noted in the skeletons. However, inflammatory arthritic changes were apparent by histopathology and immunohistochemistry (F4/80), immunofluorescence (CD206) and Cy3-tilmanocept binding. In human RA synovial fluid, Cy3-tilmanocept staining correlated with CD206 + /CD16 + cells; negligible labeling was observed in OA samples. Cy3-tilmanocept colocalized with CD206 and staining was significantly higher in RA synovial tissue compared to OA or HV. Our results demonstrate that imaging with Cy3-tilmanocept can detect in vivo inflammatory, CD206 + macrophages in an early arthritis animal model and in human RA patients. These data establish a novel tool for preclinical research of early arthritis and have implications for early RA detection and monitoring of therapeutic efficacy in humans., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Purpose: We appraised the feasibility of left ventricle (LV) function assessment using gated first-pass 18 F-FDG PET, and assessed the concordance of the produced measurements with equilibrium radionuclide angiography (ERNA)., Materials and Methods: Twenty-four oncologic patients benefited from 99m Tc-labeled red-blood-cell ERNA, in planar mode (all patients) and using SPECT (22 patients). All patients underwent gated first-pass 18 F-FDG cardiac PET. Gated dynamic PET images were reconstructed over 1 minute during tracer first-pass inside the LV and post-processed using in-house software (TomPool). After re-orientation into cardiac canonical axes and adjustment of the valves plane using a phase image, pseudo-planar PET images obtained by re-projection were automatically segmented using thresholded region growing and gradient-based delineation to produce an LV ejection fraction (EF) estimate. PET images were also post-processed in fully-tomographic mode to produce LV end diastole volume (EDV), end systole volume (ESV), and EF estimates. Concordance was assessed using Lin's concordance (ccc) and Bland-Altman analysis. Reproducibility was assessed using the coefficient of variation (CoV) and intra-class correlation (ICC)., Results: Pseudo-planar PET EF estimates were concordant with planar ERNA (ccc = 0.81, P < .001) with a bias of 0% (95% CI [- 2%; 3%], limits of agreement [- 11%; 12%]). Reproducibility was excellent and similar for both methods (CoV = 2 ± 1% and 3 ± 2%, P = NS; ICC = 0.97 and 0.92, for PET and ERNA, respectively). Measurements obtained in fully-tomographic mode were concordant with SPECT ERNA: ccc = 0.83 and bias = - 3 mL for LV EDV, ccc = 0.92 and bias = 0 mL for LV ESV, ccc = 0.89 and bias = - 1% for LV EF (all P values < .001 for ccc, all biases not significant)., Conclusions: Gated first-pass 18 F-FDG PET might stand as a relevant alternative to ERNA for LV function assessment, enabling a joint evaluation of both therapeutic response and cardiac toxicity in oncologic patients receiving cardiotoxic chemotherapy.

Bacterial infections are a serious risk to human health, and therefore techniques for early detection of infectious foci need to be further developed to begin treatment quickly and achieve better results. Antimicrobial peptides labeled with gamma-emission radio nuclides are important diagnostic radiotracers in nuclear medicine. This study was conducted to evaluate the potential of a 99m Tc-labeled MicrocinJ25 (MccJ25) antimicrobial peptide analog for early detection of infection. For this purpose, a HYNIC conjugated cyclic peptide derivative based on the primary structure of MccJ25 peptide was prepared and labeled by 99m Tc with tricine and EDDA as coligands. The [ 99m Tc-HYNIC/EDDA]-MccJ25 peptide analog showed high radiochemical purity (˃90% (n = 5)) which was stable up to 24 hr after labeling. The radiotracer showed specific uptake to the Escherichia coli (E. coli) bacterial (40.45 ± 5.21%) at 1 hr incubation. High kidneys uptake of radioactivity (4.71 ± 0.84% and 3.76 ± 0.45% ID/g at 1 and 4 hr after injection respectively) demonstrates that most of the whole body clearance was proceeded via the urinary system. Significant radioactivity uptake (1.71 ± 0.34%ID/g) was observed in thigh muscle of mouse with E. coli induced infection at 1 hr after injection. In the blocking test, due to the significant decrease of radioactivity uptake in the infection site (0.62 ± 0.21%ID/g after 1 hr), the specificity of infection uptake was reviled. Despite the high activity of the bladder due to urinary excretion, the infected area was somewhat visible. Hence, the results indicate the potential of this new radiotracer to be used as a diagnostic agent in E. coli infections., (© 2020 John Wiley & Sons A/S.)

Purpose: The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound (99mTc Nanotop) for SLN biopsy (SLNB) in breast cancer patients., Methods: The day before surgery, ICG-99mTc Nanotop was injected periareolarly in breast cancer patients scheduled for SLNB. Planar lymphoscintigraphic (PL) and SPECT/CT images were then acquired. An intraoperative optonuclear probe was used to detect SLN gamma and fluorescent signals. The harvested SLNs were examined by hematoxylin-eosin staining, and patients were clinically evaluated 1 month after surgery., Results: Twenty-one consecutive patients were enrolled. The PL and SPECT/CT techniques identified at least 1 SLN in all patients for a preoperative sentinel detection rate of 100%. SPECT/CT revealed 3 additional lymph nodes in the same nodal basin, which had not been visualized on conventional PL (κ = 0.747; P < 0.005). All 30 preoperative SLNs were localized and excised up to 16 hours after injection. The counts measured via gamma tracing showed a very strong correlation with those measured via near-infrared fluorescent tracing (P < 0.005, r = 0.964). No adverse reactions were observed., Conclusions: The SLNB technique used with the ICG-99mTc Nanotop tracer resulted to be feasible, reliable, and safe. This hybrid compound allowed us to obtain excellent performance in terms of both preoperative lymphatic mapping and intraoperative SLN detection in breast cancer patients., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)