Comparative biodistribution studies of technetium‐99 m radiolabeled amphiphilic nanoparticles using three different reducing agents during the labeling procedure

Considering the confusing biodistribution data through the literature and few reported alerts as well as our preliminary biodistribution results, we decided to evaluate the interaction and interference of the commonly present ^99mTc (technetium‐99m)‐stannic oxide colloid during the direct stannous chloride ^99mTc‐labeling procedure and to assess its influence on the biodistribution pattern of amphiphilic poly(lactic‐co‐glycolic acid) nanoparticles. In order to confirm our thesis, beside stannous chloride, we employed two different reducing agents that don't form colloidal particles. The use of sodium borohydride was previously reported in the literature, whereas sodium dithionite was adapted for the first time in the ^99mTc direct labeling procedure for nanoparticles. The results in our paper clearly differentiate among samples with and without colloidal impurities originating from the labeling procedure with a logical follow up of the radiochemical, physicochemical evaluation, and biodistribution studies clarifying previously reported data on stannic oxide colloidal interference. ^99mTc‐nanoparticle complex labeled with sodium dithionite as reducing agent illustrated appropriate labeling efficacy, stability, and potential for further use in biodistribution studies thus providing solution for the problem of low‐complex stability when sodium borohydride is used and colloidal stannic oxide interference for stannous chloride procedure. Copyright © 2013 John Wiley & Sons, Ltd.     

Lactosaminated N‐succinyl‐chitosan as a liver‐targeted carrier of 99mTc in vivo for nuclear imaging and biodistribution

Lactosaminated N‐succinyl‐chitosan (LNSC), a water‐soluble biodegradable derivative of chitosan, was prepared, characterized, and investigated for nuclear imaging and body distribution. The labeling efficiency of LNSC was examined with ^99mTc, and the obtained complex was used as liver‐targeted delivery system in vivo for nuclear imaging, and its biodistribution within the body was studied. The labeling efficiency with ^99mTc was investigated for time of reaction, effect of substrate amount, effect of stannous chloride (SnCl₂) concentration, and effect of the pH of the reaction mixture, in order to approach the optimum condition for labeling technique. It was found that the maximum yield for labeling of 2.5‐mg ^99mTc‐LNSC was 96.9% when 50 µg of SnCl₂ was used at pH 3.5–5, at room temperature and 5‐min reaction time. An in vivo biodistribution study of radiolabeled LNSC was carried out in female Wistar rats, and the body distribution profile was recorded by gamma scintigraphy. The biodistribution of ^99mTc‐labeled LNSC (^99mTc‐LNSC) in each organ was calculated as a percentage of the injected dose per gram of tissue (%ID/g). ^99mTc‐LNSC was shown to be a highly potential approach for liver imaging. Moreover, the rapid excretion of LNSC through the kidneys suggests that water‐soluble chitosan derivatives are good carriers of radioactive elements that do not accumulate in the body. The results indicate that the easy and inexpensive extraction, and thus the ready availability, of chitosan and its derivatives makes them potentially useful for applications in scintigraphic imaging.     

Synthesis of 99mTc‐labeled organo‐germanium nanoparticles and their in vivo study as a spleen imaging agent

^99mTc‐Labeled organo‐germanium nanoparticles ranging in size from 60 to 80 nm were newly developed for a spleen imaging agent. The radiolabeled nanoparticles were prepared with a high labeling efficiency (over 99%) and they also showed an excellent stability at room temperature for 6 h. The biodistribution data of the nanoparticles injected into rats via intravenous routes showed a notably higher accumulation in the spleen when compared to other reticuloendothelial system organs. Gamma image of the rabbits obtained after an intravenous injection of the nanoparticles revealed a localization of the radioactivity mainly in the spleen and the liver. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis and in vivo evaluation of 99m Tc-Transferrin conjugate for detection of inflamed site

Transferrin is one of acute phase reactants in inflamed lesion. Expression of transferrin receptor is increased in activated macrophage during inflammation process. Conjugates of target ligand with novel water-soluble chitosan for fast excretion of background radioactivity have been shown to be selectively taken up via the target molecules. In this study, radiolabeled 99m Tc-Transferrin conjugate was synthesized and evaluated its efficacy in vivo as a targeted agent for the rapid detection of inflamed lesion that expresses relatively high level of transferrin receptors. Transferrin was conjugated with HYNIC-chitosan and radiolabeled with 99m Tc. The biodistribution and scintigraphic images with the 99m Tc-HYNIC-chitosan-Transferrin conjugate (99m Tc-Tfc) were studied in a murine infection model in which the infection was induced with Escherichia coli (2 x 10(6) colonies). The %ID/g was as follows: 1.612 +/- 0.098, 2.473 +/- 0.202 and 2.617 +/- 0.646% at 30, 120 min and 6 h after injection, respectively. Gamma camera imaging rapidly visualized the infection/inflammation lesion, with the lesion-to-background ratio improving with time up to 5.68 +/- 0.48. 99m Tc-Tfc scintigraphy allows rapid and good imaging of an inflamed lesion.     

Synthesis and in vivo evaluation of 99mTc–Transferrin conjugate for detection of inflamed site

Transferrin is one of acute phase reactants in inflamed lesion. Expression of transferrin receptor is increased in activated macrophage during inflammation process. Conjugates of target ligand with novel water-soluble chitosan for fast excretion of background radioactivity have been shown to be selectively taken up via the target molecules. In this study, radiolabeled ^99mTc–Transferrin conjugate was synthesized and evaluated its efficacy in vivo as a targeted agent for the rapid detection of inflamed lesion that expresses relatively high level of transferrin receptors. Transferrin was conjugated with HYNIC-chitosan and radiolabeled with ^99mTc. The biodistribution and scintigraphic images with the ^99mTc–HYNIC–chitosan–Transferrin conjugate (^99mTc–Tfc) were studied in a murine infection model in which the infection was induced with Escherichia coli (2 × 10⁶ colonies). The %ID/g was as follows: 1.612 ± 0.098, 2.473 ± 0.202 and 2.617 ± 0.646% at 30, 120 min and 6 h after injection, respectively. Gamma camera imaging rapidly visualized the infection/inflammation lesion, with the lesion-to-background ratio improving with time up to 5.68 ± 0.48. ^99mTc–Tfc scintigraphy allows rapid and good imaging of an inflamed lesion.     

Enhanced Tumour Uptake of Doxorubicin Loaded Poly(butyl cyanoacrylate) Nanoparticles in Mice Bearing Dalton's Lymphoma Tumour

The objective of this study is to enhance the delivery of Doxorubicin hydrochloride to Dalton's lymphoma solid tumour through poly(butyl cyanoacrylate) (PBC) nanoparticles. Doxorubicin loaded PBC (DPBC) nanoparticles were prepared by emulsion polymerization and characterized by particle size analysis, zeta potential and scanning electron microscopy. Doxorubicin HCl (Dox) and DPBC nanoparticles were radiolabeled with ^99mTc by reduction method using stannous chloride and optimized the labeling parameters to obtain high labeling efficiency. The in vitro stability of ^99mTc-labeled complexes was determined by DTPA and cysteine challenge test. The labeled complexes showed very low transchelation and high in vitro and serum stability. ^99mTc labeled complexes of Dox and DPBC nanoparticles were administered subcutaneously below the Dalton's lymphoma tumour and biodistribution was studied. The distribution of DPBC nanoparticles to the blood, heart and organs of RES such as liver, lung and spleen was biphasic with a rapid initial distribution, followed by a significant decrease later at 6 h post-injection. The distribution of Dox to tissues was very low initially and increased significantly at 6 h post-injection indicating its accumulation at the injection site for a longer time. The concentration of DPBC nanoparticles was also found high in tissues at 6 h post-injection indicating their accumulation at the subcutaneous site and consequent disposition to tissues with time. A significantly high tumour uptake of DPBC nanoparticles (～13 fold higher at 48 h post-injection) (P <0.001) was found compared to free Dox. The tumour concentrations of both Dox and DPBC nanoparticles increased with time indicating their slow penetration from the injection site into tumour. The concentration of DPBC nanoparticles in the femur bone in the tumour region was also significantly higher (P <0.001) than free Dox and increased with time. The study signifies the advantage of delivering Dox to Dalton's lymphoma through PBC nanoparticles by facilitating enhanced tumour uptake and prolonged tumour retention, which are expected to lead to greater therapeutic effect in the form of tumour regression.     

Radiolabeling, pharmacoscintigraphic evaluation and antiretroviral efficacy of stavudine loaded 99mTc labeled galactosylated liposomes.

The study was aimed to optimize radiolabeling with 99mTc, to determine the antiretroviral activity and to study the biodistribution of 99mTc labeled galactosylated liposomes loaded with stavudine. Liposomes were prepared using reverse-phase evaporation method followed by extrusion through 200nm polycarbonate membranes. The galactosylated liposomes were assessed for in vitro ligand-specific activity and the aggregation of galactosylated liposomes was found to increase as lectin concentration was increased from 5microg/ml to 30microg/ml. Free stavudine and stavudine loaded plain and galactosylated liposomes were radiolabeled with 99mTc by direct labeling method using stannous chloride as a reducing agent. Labeling method was optimized for stannous chloride quantity to achieve maximum labeling efficiency >95%. Antiretroviral activity was determined using human immunodeficiency virus-1 (HIV) infected MT2 cell line. A dose-dependent inhibition of p24 production was observed upon treatment of HIV-1 infected MT2 cells with stavudine loaded liposomes and galactosylated liposomes. Scintigraphic imaging and quantitative biodistribution of 99mTc labeled drug and liposomes showed that liposomal formulations were better taken up by the liver and spleen. Free drug solution was cleared from the blood. Further, a significantly higher (P<0.05) liver and spleen retention was observed over a period of 24h in case of galactosylated liposomes as compared to free drug and plain liposomes. Reduced uptake of the galactosylated liposomes in bone and higher and prolonged accumulation in mononuclear phagocyte system (MPS)-rich organs indicates the excellent potential of this formulation in the treatment of HIV infection.     

99mTc标记的大肠癌单克隆抗体在小鼠体内分布特点的研究

目的：研究^99m-Tc标记的大肠癌单克隆抗体(^99mTc—ACCmAb)在正常小鼠和荷瘤裸鼠体内的分布及在荷瘤裸鼠体内SPECT成像的研究。方法：将^99m-Tc和^99mTc—ACCmAb分别注射入正常小鼠、荷L010-16人结肠癌裸鼠，按不同时间点采取小鼠的脏器进行同位素放射性活度的测定；并在不同时间测定荷L010-16人结肠癌裸鼠注射^99mTc—ACCmAb的SPECT显像。结果：注射^99mTc后正常小鼠体内6h5min血液中的放射性活度与30min相比下降了76．6％，是30min的23．4％；肝脏中6h5min的放射性活度为30min的27．2％，下降了72．8％。尾静脉注射^99mTc-ACCmAb的正常小鼠，6h5min在血液中的放射性活度与30min血液中的放射性活度比较下降了68．4％，是30min的31．6％，24h为6h5min的6．1％，下降了93．9％；荷瘤裸鼠体内^99mTc-ACCmAb在24h血液中的放射性活度是6h5min的2．1％，下降了97．9％。SPECT显像结果表明，虽然在注射^99mTc-ACCmAb20h血液与肿瘤的比值为最高，但在24h的成像结果仍然好于其他的时间点。结论：^99m-Tc标记的大肠癌单克隆抗体可特异性浓聚于荷L010-16人结肠癌裸鼠模型中，可能成为大肠癌根除手术中使用的手术导向体内诊断用药，保证手术切除肿瘤的彻底性。     

Radiosynthesis,biodistribution and scintigraphy of the 99mTc‐Teicoplanin complex in artificially infected animal models

Radiocomplexation of Teicoplanin (TIN), a new glycopeptide antibiotic with technetium‐99m, was investigated. The ^99mTc‐TIN complex was assessed for its radiochemical permanence, in vitro stability in serum, binding with methicillin‐resistant Staphylococcus aureus (MRSA), biodistribution in Model Rats (MRT) and for scintigraphic precision in Model Rabbit (MRB). Radiochemically, a stable ^99mTc‐TIN was observed with 98.90±0.50% yield and remained staunch more than 90% up to 120 min, by mixing TIN, 1.5 mg in 0.5 ml of saline with 2.5 mCi sodium pertechnetate and 150 µl of stannous chloride dihydrate at pH 5.4. The ^99mTc‐TIN was found stable in serum with an insignificant undesirable yield of free and unhydrolyzed technetium (5.25±0.10 and 13.5±0.14%, n = 10) up to 120 min of incubation. The ^99mTc‐TIN showed in vitro binding with MRSA in the range of 55–65%. The ^99mTc‐TIN showed almost six‐fold elevated uptake in the infected (IFT) muscle of the MRT as compared with the inflamed (IFM) and normal (NL) muscles. This higher uptake of the ^99mTc‐TIN in the IFT was scintigraphically confirmed after the whole body scanning of the MRB. The radiochemical eternalness with high yield, in vitro stability in serum, binding with MRSA, significant biodistribution performance, and scintigraphic precision posed the ^99mTc‐TIN, a new glycopeptide radiotracer for the infection imaging. Copyright © 2010 John Wiley & Sons, Ltd.     

Technetium‐99 m labeling and evaluation of olsalazine: a novel agent for ulcerative colitis imaging

Ulcerative colitis is a chronic disease having a regressive nature. Commonly used diagnostic methods have the disadvantage to be invasive, time‐consuming, and expensive. Therefore, a new sensitive method for the detection and monitoring of disease activity is urgently needed in clinical practice. In the current investigation, radio complexation of olsalazine with technetium‐99m, its characterization, and optimization of the labeling conditions were explored. Optimum radiochemical yield of ^99mTc‐olsalazine (97.6% ± 1.8%) was obtained via direct complexation with technetium‐99m (~200 MBq) in the presence of stannous chloride dihydrate (100 µg) as reducing agent at pH 6. It was observed that the complex showed significant in vitro stability in serum at 37°C for more than 11 h. The computer‐generated optimized geometries of the ^99mTc‐olsalazine were reported, and biodistribution studies were carried out using chemically and microbiologically mice‐induced ulcerative colitis models. The tracer showed a good localization in both models and was excreted mainly via liver and to some extent via kidney. Imaging can be performed at 1–2 h post‐injection; at that time, the background activity has cleared, and the activity is concentrated in the target site. All the gathered biological data supported the usefulness of ^99mTc‐olsalazine as a potential imaging agent for ulcerative colitis.     

Chloramphenicol-incorporated poly lactide-co-glycolide (PLGA) nanoparticles: formulation, characterization, technetium-99m labeling and biodistribution studies

Chloramphenicol-loaded (CHL) poly-d,l-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were prepared by emulsification solvent evaporation technique either by using polyvinyl alcohol (PVA) as emulsion stabilizer or polysorbate-80 (PS-80) as surfactant and characterised by transmission electron microscopy, zeta-potential measurements. The NPs were radiolabeled with technetium-99m ((99m)Tc) by stannous reduction method. Labeling conditions were optimised to achieve high-labeling efficiency, in vitro and in vivo (serum) stability. The labeled complexes also showed very low transchelation as determined by DTPA challenge test. Biodistribution studies of (99m)Tc-labeled complexes were performed after intravenous administration in mice. The CHL-loaded PLGA NPs coated with PS-80 exhibited relatively high brain uptake with comparatively low accumulation in bone marrow to that of free drug and CHL-loaded PLGA NPs (PVA, used as emulsion stabilizer) at 24 h post injection time period. This indicates the usefulness of the above delivery system for prolonged use of the antibiotic.     

Effect of mitomycin-C on the bioavailability of the radiopharmaceutical (99m)technetium-phytic acid in mice: a model to evaluate the toxicological effect of a chemical drug.

The many desirable characteristics of technetium-99m ((99m)Tc) have stimulated the development of labelling techniques for different molecular and cellular structures. It is generally accepted that a variety of factors can alter the biodistribution of radiopharmaceuticals and one such factor is drug therapy. Because patients on chemotherapeutic treatment receive a radiopharmaceutical in a nuclear medicine procedure, we have studied in Balb/c mice the effect of mitomycin-C on the biodistribution of the radiopharmaceutical (99m)Tc-phytic acid ((99m)Tc-PHY) used in hepatic scintigraphy. Mitomycin-C is an antineoplastic agent obtained from Streptomyces caesptosus and is used on the treatment of disseminated adenocarcinoma of the stomach or pancreas. Three doses of mitomycin-C were administered via the ocular plexus into Balb/c mice. One hour after the last dose, (99m)Tc-PHY was administered and the animals were sacrificed. The organs were isolated, the radioactivity was determined in a well counter and the percentages of radioactivity in the organs were calculated. The results have shown that the percentage radioactivity has been increased in stomach, spleen, lung, thyroid and bone, decreased in pancreas and thymus and not altered in ovary, uterus, kidney, heart, liver and brain. The changes in the distribution of (99m)Tc-PHY may be the result of metabolic processes and/or therapeutic actions produced by the administration of mitomycin-C.     

99mTc‐aprotinin – optimisation and validation of radiolabelling kits for routine preparation for diagnostic imaging of amyloidosis

Technetium‐99m aprotinin was prepared from an optimised radiolabelling kit formulation containing aprotinin, alkaline buffer and stannous chloride (reducing agent) and radiolabelled using ^99mTc‐pertechnetate. The labelling was achieved within 25 min, with radiochemical purities of >98%.     

Use of a HEHEHE purification tag instead of a hexahistidine tag improves biodistribution of affibody molecules site-specifically labeled with (99m)Tc, (111)In, and (125)I

Affibody molecules are a class of small (～7 kDa) robust scaffold proteins suitable for radionuclide molecular imaging in vivo. The attachment of a hexahistidine (His(6))-tag to the Affibody molecule allows facile purification by immobilized metal ion affinity chromatography (IMAC) but leads to high accumulation of radioactivity in the liver. Earlier, we have demonstrated that replacement of the His(6)-tag with the negatively charged histidine-glutamate-histidine-glutamate-histidine-glutamate (HEHEHE)-tag permits purification of Affibody molecules by IMAC, enables labeling with [(99m)Tc(CO)(3)](+), and provides low hepatic accumulation of radioactivity. In this study, we compared the biodistribution of cysteine-containing Affibody molecules site-specifically labeled with (111)In, (99m)Tc, and (125)I at the C-terminus, having a His(6)-tag at the N- or C-terminus or a HEHEHE-tag at the N-terminus. We show that the use of a HEHEHE-tag provides appreciable reduction of hepatic radioactivity, especially for radiometal labels. We hope that this information can also be useful for development of other scaffold protein-based imaging agents.     

Physico‐chemical characterisation of 99mTc‐tin fluoride colloid agent used for labelling white cells

^99mTc–tin fluoride colloid is an agent used to label leucocytes, for the imaging and diagnosis of inflammatory conditions including Crohn's disease. Despite previous investigations, this radiolabelling agent is still poorly characterised. The aim of this work was to examine the process of formation and stability of ^99mTc–tin fluoride colloid using mass spectrometry, membrane filtration and atomic absorption spectrophotometric techniques. Tin‐oxide bonds in tin clusters were identified in the stannous fluoride reagent vial by mass spectrometry. From radioactive particle size distribution experiments, the facile disruption of radiocolloid particles with excess oxygen gas contrasted to the partial hydrolysis of Sn(II) during the formation process. Under the standard conditions, 10% of particles were determined as 1–3 µm, and this population coordinated 96% of the ^99mTc added. Colloid particle formation and the reduction of ^99mTc‐pertechnetate is discussed. Sodium fluoride may optimise 1–3 µm radioactive particle size, by regulating particle growth. ^99mTc–tin fluoride colloid is affected by positive or negative charge, as either Al, Mo ions or solid membranes, resulting in either coagulation and/or deflocculation of the particles. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis and biological evaluation of radiolabeled photosensitizer linked bovine serum albumin nanoparticles as a tumor imaging agent

In this study, we reported on the synthesis and biological evaluation of radiolabeled fluorescent dye conjugated bovine serum albumin nanoparticles within the size range 190-210 nm. The bovine serum albumin nanoparticles (BSANPs) were prepared using a desolvation method, and chemical cross-linking was performed using gluteraldehyde. Furthermore, pheophorbide-a (PH-A) was loaded on the BSANPs. The results obtained from dynamic light scattering and electron microscopy have proved that nanoparticles are highly monodisperse and near-spherical shaped. The photo-physical properties of the PH-A-BSANPs were obtained using the spectrophotometric techniques. According to the results, PH-A and BSANPs show high non-covalent interaction. PH-A loaded nanoparticles were labeled with (99m)Tc and the radio-labeling efficiency was determined as 90 ± 1.2%. Biodistribution studies of (99m)Tc labeled PH-A-BSANPs and PH-A were carried out using female Albino Wistar rats, and (99m)Tc-PH-A-BSANPs showed a significantly higher uptake in the breast and uterus than (99m)Tc-PH-A. Cell culture study was carried out in MCF-7 cell line (human breast adenocarcinoma cell line). According to the cell culture studies, (99m)Tc-PH-A-BSANPs showed a higher uptake than (99m)Tc-PH-A. Moreover, PH-A-BSANPs demonstrated good photo-physical properties and BSANPs increased the uptake of PH-A on to the MCF-7 cell line. These results confirm that (99m)Tc labeled PH-A-BSANPs could be utilized for radioimaging.     

Enhanced tumour uptake of doxorubicin loaded poly(butyl cyanoacrylate) nanoparticles in mice bearing Dalton's lymphoma tumour

The objective of this study is to enhance the delivery of Doxorubicin hydrochloride to Dalton's lymphoma solid tumour through poly(butyl cyanoacrylate) (PBC) nanoparticles. Doxorubicin loaded PBC (DPBC) nanoparticles were prepared by emulsion polymerization and characterized by particle size analysis, zeta potential and scanning electron microscopy. Doxorubicin HCl (Dox) and DPBC nanoparticles were radiolabeled with 99mTc by reduction method using stannous chloride and optimized the labeling parameters to obtain high labeling efficiency. The in vitro stability of 99mTc-labeled complexes was determined by DTPA and cysteine challenge test. The labeled complexes showed very low transchelation and high in vitro and serum stability. 99mTc labeled complexes of Dox and DPBC nanoparticles were administered subcutaneously below the Dalton's lymphoma tumour and biodistribution was studied. The distribution of DPBC nanoparticles to the blood, heart and organs of RES such as liver, lung and spleen was biphasic with a rapid initial distribution, followed by a significant decrease later at 6 h post-injection. The distribution of Dox to tissues was very low initially and increased significantly at 6 h post-injection indicating its accumulation at the injection site for a longer time. The concentration of DPBC nanoparticles was also found high in tissues at 6 h post-injection indicating their accumulation at the subcutaneous site and consequent disposition to tissues with time. A significantly high tumour uptake of DPBC nanoparticles (approximately 13 fold higher at 48 h post-injection) (P <0.001) was found compared to free Dox. The tumour concentrations of both Dox and DPBC nanoparticles increased with time indicating their slow penetration from the injection site into tumour. The concentration of DPBC nanoparticles in the femur bone in the tumour region was also significantly higher (P <0.001) than free Dox and increased with time. The study signifies the advantage of delivering Dox to Dalton's lymphoma through PBC nanoparticles by facilitating enhanced tumour uptake and prolonged tumour retention, which are expected to lead to greater therapeutic effect in the form of tumour regression.     

Characterization of Re-188-Sn microparticles used for synovitis treatment

Rhenium-188 labeled tin (Sn) microparticles were developed for pain palliation therapy in the patients suffering from synovitis with acute pain. The rhenium tin microparticles were prepared using stannous chloride and freshly eluted (188)ReO(4)(-) from (188)W/(188)Re generator. The aggregated colloidal particles, packed in a spherical form after boiling for 90-120min were analyzed using electron microscope. The size, surface morphology and stability of microparticles were analyzed by changing temperature and volume conditions. The small colloidal particles clustered and formed spherical microparticles. The 90% of microparticles were in 5-10microm range, after 90min and 120min of boiling. The radiolabeling efficiency was improved to 98% after centrifugation for 10min at 3500rpm. The formulations were stable but the increase in volume had inverse effect on labeling efficiency. No leak was observed from knee area up to 24h with 15-20mCi injection of (188)Re-Sn microparticles. The relief in treated patients, from the pain and inflammation, was observed clinically and by (99m)Tc-MDP perfusion scan.     

99mTc-Methionine Gold Nanoparticles as a Promising Biomaterial for Enhanced Tumor Imaging

Methionine-gold nanoparticles (MGNs) was synthesized by conjugating methionine via dithiocarbamate linkage to gold nanoparticles (GNPs), prepared simultaneously by one pot modified Burst method. Formation of MGNs was confirmed by UV-visible spectroscopy and appearance of new IR bands in the range of 934 cm^?1 to 1086 cm^?1 and shifting of N-C,S-S and S-C-S stretching, confirms the involvement of ‘-S-C-S-’ group of methionine dithiocarbamate with GNPs. The presence of Au in MGNs was confirmed by EDXA spectrum, whereas TEM, SAED and XRD revealed that MGNs are nanocrystalline (~13 nm) and have face-centered cubic structure. MGNs was labeled with ^99mTc (TMGNs) with radiolabeling efficiency greater than 99% using 300 μg of stannous chloride, pH 7 and 90.6 MBq of ^99mTcO₄. The stability data showed that the conjugate will remain infrangible in systemic circulation and in acidic microenvironment of tumor. The blood kinetic profile of TMGN in rabbits and biodistribution studies in EAT tumor bearing balb/c mice showed longer in vivo circulation and slow clearance compared to radiolabeled methionine (TM). TMGN demonstrated nearly three-fold higher tumor accumulation (3.9 ± 0.35% ID/g), 2-fold lower tumor saturation dose (1.0 μg/kg) and higher tumor retention compared with TM. Data showed that the TMGN tumor: blood ratio (1.05) is nearly 2.5-fold higher than TM (0.44), whereas TMGN tumor: muscle ratio (97.5) is nearly 8-fold higher than TM (11.6). In conclusion, TMGN showed excellent tumor targeting and has promising prospects as a SPECT-radiopharmaceutical for imaging tumors.     

99mTc‐tazobactam,a novel infection imaging agent: Radiosynthesis,quality control,biodistribution, and infection imaging studies

The radiolabeled drug ^99mTc‐tazobactam (^99mTc‐TZB) was developed and assessed as an infection imaging agent in Pseudomonas  aeruginosa and Salmonella  enterica infection–induced animal models by comparing with inflammation induced animal models. Radiosynthesis of ^99mTc‐TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the ^99mTc‐TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed ^99mTc‐TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues.