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This study aims to investigate radiolabeled Cefpodoxime Proxetil loaded chitosan (CP–CS) nanoparticles as nuclear imaging infection agent to Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). The encapsulation efficiency of Cefpodoxime Proxetil was found 82 ± 2%. CP and CP–CS nanoparticles were radiolabeled with Tc-99 m. The radiochemical purity of 99mTc–CP and 99mTc–CP–CS nanoparticles were determined by RTLC as 89 ± 3% and 94 ± 2% respectively. In vitro bindings of 99mTc–CP–CS nanoparticles to S. aureus and E. coli were found higher than 99mTc–CP bindings. © 2020, Akadémiai Kiadó, Budapest, Hungary.

Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [Tc-99m]Tc-(HE)(3)-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)(3)), provided clear imaging of HER2 expressing breast cancer 2-4 h after injection. The goal of this study was to evaluate if the use of cysteine-containing peptide-based chelators Glu-Glu-Glu-Cys (E3C), Gly-Gly-Gly-Cys (G(3)C), and Gly-Gly-Gly-Ser-Cys connected via a (Gly-Gly-Gly-Ser)(3)-linker (designated as G3-(G(3)S)(3)C) would further improve the contrast of imaging using Tc-99m-labeled derivatives of G3. The labeling of the new variants of G3 provided a radiochemical yield of over 95%. Labeled G3 variants bound specifically to human HER2-expressing cancer cell lines with affinities in the range of 1.9-5 nM. Biodistribution of [Tc-99m]Tc-G3-G(3)C, [Tc-99m]Tc-G3-(G(3)S)(3)C, and [Tc-99m]Tc-G3-E3C in mice was compared with the biodistribution of [Tc-99m]Tc-(HE)(3)-G3. It was found that the novel variants provide specific accumulation in HER2-expressing human xenografts and enable discrimination between tumors with high and low HER2 expression. However, [Tc-99m]Tc-(HE)(3)-G3 provided better contrast between tumors and the most frequent metastatic sites of HER2-expressing cancers and is therefore more suitable for clinical applications.

4th International Conference on Computational and Experimental Science and Engineering (ICCESEN) -- OCT 04-08, 2017 -- Kemer, TURKEY WOS: 000478894500038 To date, myocardial perfusion (MP) has been utilized to assess the adequacy of blood flow to the myocardium in order to determine the ischemic heart diseases. With the advent of SPECT/CT, MP became the most common investigation in the field of nuclear cardiology with more accuracy and details. Thallium-201 and Technetium-99m (Tc-99m) have been early used in cardiac nuclear imaging. Half-life of Tc-99m is 6 h, and its energy is 140 keV, while the half-life of Tl-201 is as longer as 73 h, its X-ray energies range between 69 and 81 kV in addition to gamma rays of 135 keV and 167 keV. The purpose of the present study was to explore the radiation dose rates emitted from the patients following Tc-99m sestamibi injection. To achieve that, the radiation emanated to the environment was measured at different distances from patients and various time intervals for 20 patients using GM counter. The mean radioactivity administered to the patients was 391.1 MBq (10.6 mCi), with a range between 276.8 MBq to maximum of 515.4 MBq. Radiation dose rate was found 9.07 mu Sv h(-1) at 1 m distance from the patient's chest level after 7.6 min, then decayed to 7.93 mu Sv h(-1) after 36.5 min, and 7.83 mu Sv h(-1) later to 66.4 min. It was concluded that 1 m distance from the patients sounds sensibly adequate to maintain the occupational dose within the safe limit following Tc-99m sestamibi injection, while verification of public dose rate

Background: The [99mTc][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 [99mTc][Tc(N)(PNP)]-tagged cRGDfK peptide to determine the best performing agent and to select the framework useful for the preparation of [99mTc][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[99mTc][Tc(N)(PNP3OH)]– and [99mTc][Tc(N)(PNP3)]– are better performing synthons in terms of labeling efficiency and in vivo performance than the [99mTc][Tc(N)(PNP43)] framework and are therefore more suitable for further radiopharmaceutical purposes. Furthermore, the good labeling properties of the ws[99mTc][Tc(N)(PNP3OH)]– framework can be exploited to extend this technology to the labeling of temperature-sensitive biomolecules suitable for SPECT imaging.

In this study Isoniazid (INH) as one of the first line drugs in treatment of Tuberculosis was investigated to be loaded in Solid Lipid Nanoparticles (SLNs) for reducing hepatotoxicity as well as prolonging drug release. High shear homogenization method was performed to prepare INH SLNs. To compare biodistribution of INH before and after loading in SLNs, INH was labeled by Technetium 99 (Tc99) after derivatization. The particle size of the prepared SLNs was 167 and 200 nm before and after lyophilization, respectively. Loading efficiency was calculated using the reverse method and release study was performed by using the dialysis sack method. Loading efficiency was 98%, and more than 85% of the loaded drug released in 3 h. Differential Scanning calorimeter (DSC) studies were performed for evaluating of the probability of happening hydrogen bonds or other chemical interactions between cholesterol as carrier and isoniazid as active pharmaceutical ingredient. The results could support the probability of hydrogen bond formation between cholesterol and INH. Gamma Scintigraphy studies showed that after administering INH SLNs, longer drug retention in the body was obtained compared to free INH. Quantitative gamma counting showed that the concentration of INH in the liver and intestines could be decreased by using nanotechnology.

IntroductionRadionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of leucocyte kinetics, to the next goal of positron emission tomography (PET).Sources of dataMostly the authors’ own studies, following on from studies of the early pioneers.Areas of controversyFrom early imaging studies, it appeared that the majority of the marginated granulocyte pool was located in the lungs. However, later work disputed this by demonstrating the exquisite sensitivity of granulocytes to ex vivo isolation and labelling, and that excessive lung activity is artefactual.Areas of agreementFollowing refinement of labelling techniques, it was shown that the majority of marginated granulocytes are located in the spleen and bone marrow. The majority of leucocytes have a pulmonary vascular transit time only a few seconds longer than erythrocytes. The minority showing slow transit, ~5% in healthy persons, is increased in systemic inflammatory disorders that cause neutrophil priming and loss of deformability. Using a range of imaging techniques, including gamma camera imaging, whole-body counting and single photon-emission computerized tomography, labelled granulocytes were subsequently used to image pulmonary trafficking in lobar pneumonia, bronchiectasis, chronic obstructive pulmonary disease and adult respiratory distress syndrome.Growing pointsMore recently, eosinophils have been separated in pure form using magnetic bead technology for the study of eosinophil trafficking in asthma.Areas timely for developing researchThese include advancement of eosinophil imaging, development of monocyte labelling, development of cell labelling with PET tracers and the tracking of lymphocytes.

Use of highly-enriched uranium (HEU) at research reactors or the exporting of HEU for humanitarian purposes, such as for the production of medical isotopes, leads to a risk of nuclear proliferation. This thesis will discuss efforts to improve the understanding of low-enriched uranium (LEU) to enable more accurate predictions of the material behavior during manufacturing and use as an irradiation target for the production of medical isotope Tc-99m and as a reactor fuel. The α-phase (orthorhombic crystal structure) LEU foils proposed for use in the production of medical isotope Tc-99m have anisotropic properties due to the crystallographic texture which is introduced during the foil rolling process. This was previously demonstrated using physics-based viscoplastic self-consistent (VPSC) modeling, which used the deformation-induced texture as an input [1]. A phenomenological, analytical model for the anisotropic yield stress behavior of orthotropic, hexagonal metals was developed by Cazacu, Plunkett, and Barlat [2], denoted CPB06. A MATLAB optimization routine was used to determine values for the anisotropy coefficients used in the model, by fitting to the VPSC predictions. CPB06 was implemented as a user-subroutine (VUMAT) in ABAQUS/Explicit, a commercial finite element analysis (FEA) software, which allowed for finite element simulation of the irradiation target manufacturing process. FEA simulations ultimately revealed that while the plastic anisotropy of the foil could potentially change the strength of the material relative to the isotropic case under certain loading conditions, anisotropy did not noticeably affect the foil strength when under internal pressure, and the performance of the Tc-99m target was not affected. The -phase stabilized LEU-10Mo (wt%) alloy has been identified as a candidate fuel for high performance research reactors, though there are concerns regarding phase and mechanical stability under reactor conditions, especially during transient conditions. In-situ neutron diffraction performed at the Los Alamos Neutron Science Center (LANSCE) was used to investigate phase decomposition behavior in U-10Mo and U-9.8Mo with 0.2 wt% ternary additions of Cr, Ni, or Co, thus maintaining the total alloy content in all four alloys at 10 wt%. Since the metastable BCC phase γ-U is optimal, it is critical to understand whether or not such alloying additions delay or promote phase decomposition. These alloying additions were chosen for research since they are readily available, and come in different unit-cell structures (BCC, FCC, and HCP). During the in-situ experiments performed on the Spectrometer for Materials Research at Temperature and Stress (SMARTS), the samples were first heated at a rate of 50 ºC/min to ~650 ºC, which is above the γ-phase solvus line, and held for 1 hour to dissolve any fine, second phase particles which may have precipitated during prior heating and homogenization steps. Then, the samples were cooled at a rate of 50 ºC/min to the isothermal hold temperatures of interest, 490 or 500 ºC, and held for 20 hours to observe the kinetics of decomposition of the metastable γ-U-Mo phase toward the equilibrium α-U and γ’ (U2Mo) phases. Finally, the samples were cooled to room temperature at a rate of 50 ºC and remeasured ex-situ, both in SMARTS and in the High Intensity Pressure and Preferred Orientation (HIPPO) instrument. Rietveld analysis using the GSAS-II and MAUD software packages was employed to determine the phase fractions, lattice parameters, and crystallographic texture of all the observed phases. Experiments conducted on U-10Mo and U-9.8Mo-0.2Cr did not exhibit measurable phase decomposition. However, some phase evolution was observed in the U-9.8Mo-0.2Ni and U-9.8Mo-0.2Co alloys, which included development of the orthorhombic α-U phase along with a corresponding molybdenum-rich, and perhaps ordered, version of the BCC γ-phase, here denoted γb. Hence, it is concluded that Ni and Co ternary additions degrade the thermal stability of U-10Mo, while Cr additions do not have an observable effect. It is hypothesized that the more rapid phase evolution in the Ni and Co containing alloys is due to heterogeneous nucleation associated with the presence of small grain boundary precipitate phases, including U6Co and U6Ni, which were previously observed by SEM [3], and whose presence is corroborated by the presence of a small, solitary neutron diffraction peak in the experiments performed on U-9.8Mo-0.2Co.

Purpose: Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m labelled Cbl derivative ([99mTc]PAMA(4)-Cbl) for targeting infections caused by Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed by biodistribution studies in a mouse model of foreign body infection. Procedures: E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test strains. [57Co]Cbl, [67Ga]citrate and [99mTc]DTPA served as reference compounds. The in vitro competitive binding of [57Co]Cbl or [99mTc]PAMA(4)-Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 °C. A cage mouse model of infection was used for biodistribution of intravenous [57Co]Cbl and [99mTc]PAMA(4)-Cbl in cage and dissected tissues of infected and non-infected mice. Results: Maximum binding (mean ± SD) of [57Co]Cbl to viable E. coli was 81.7 ± 2.6 % and to S. aureus 34.0 ± 6.7 %, at 37 °C; no binding occurred to heat-killed bacteria. Binding to both test strains was displaced by 100- to 1000-fold excess of unlabeled Cbl. The in vitro binding of [99mTc]PAMA(4)-Cbl was 100-fold and 3-fold lower than the one of [57Co]Cbl for E. coli and S. aureus, respectively. In vivo, [99mTc]PAMA(4)-Cbl showed peak percentage of injected dose (% ID) values between 1.33 and 2.3, at 30 min post-injection (p.i.). Significantly higher retention occurred in cage fluids infected with S. aureus at 4 h and with E. coli at 8 h p.i. than in non-infected animals. Accumulation into infected cages was also higher than the one of [99mTc]DTPA, which showed similar biodistribution in infected and sterile mice. [57Co]Cbl gradually accumulated in cages with peaks % ID between 3.58 and 4.83 % achieved from 24 to 48 h. Discrimination for infection occurred only in E. coli-infected mice, at 72 h p.i. [67Ga]citrate, which showed a gradual accumulation into cage fluids during 12 h, was discriminative for infection from 48 to 72 h p.i. (P, Molecular Imaging and Biology, 17 (6), ISSN:1860-2002, ISSN:1536-1632

In the present work, we investigated potential means to obtain neutral tricarbonyl mixed-ligand fac-[M(CO)(3)(LL2)-L-1] complexes (M = Re, Tc-99m) containing the (2-hydroxyphenyl)diphenylphosphine (POH) bidentate ligand ((LH)-H-1) and a series of monodentate ligands (L-2). First, fac[Re(CO)(3)(PO)(H2O)], 1, was synthesized by reaction of POH and [Et4N](2)[Re(CO)(3)Br-3] in equimolar amounts in MeOH at room temperature. Interestingly, with excess of POH this reaction afforded fac-[Re(CO)(3)(PO)(POH)], 2, with POH operating both as a bidentate and as a monodentate ligand. Owing to the presence of the labile aqua ligand, which can be readily replaced by various monodentate ligands, 1 was further used as a precursor to generate a small library of the desired fac-[M(CO)(3)(LL2)-L-1] complexes. Specifically, by reaction of triphenylphosphine (PPh3), imidazole (im), pyridine (py), cyclohexyl isocyanide (cisc), and tert-butyl isocyanide (tbi), the following products were readily obtained in excellent yields (92%-95%): fac-[Re(CO)(3)(PO)(PPh3)], 3, fac-[Re(CO)(3)(PO)(im)], 4, fac-[Re(CO)(3)(PO)(py)], 5, fac-[Re(CO)(3)(PO)(CiSc)], 6, and fac-[Re(CO)(3)(PO)(tbi)], 7. All compounds were fully characterized by elemental analysis, IR and NMR spectroscopies, and electrospray ionization(+) mass spectrometry. Their solid-state structure was elucidated by X-ray crystallography. Of considerable interest is the fact that the corresponding 2'-7' were easily accessible at the Tc-99m-tracer level in quantitative yields after reaction of POH and the respective monodentate ligand L-2 with fac-[Tc-99m(CO)(3)(H2O)(3)] in aqueous MeOH, as verified by comparative chromatographic methods adopting dual photo and radiometric detection modes. The high stability displayed by all Tc-99m complexes during histidine and cysteine challenge assays underscored the suitability of the fac-[M(CO)(3)(PO)L-2] system for radiopharmaceutical development purposes.

Background Image-based measurement of absorbed dose of Ra-223 dichloride may be useful in predicting therapeutic outcome in patients with castration-resistant prostate cancer (CRPC). In general, SPECT has been found to be more accurate than planar imaging in terms of lesion-based analysis. The aims of this study were to assess the feasibility and clinical usefulness of Ra-223 SPECT. The energy spectrum of Ra-223 and SPECT images of a cylindrical phantom with a hot rod were obtained to determine the collimator candidates and energy window settings suitable for clinical Ra-223 SPECT (basic study A). Another phantom with a tube-shaped chamber and two spheres simulating bowel activity and metastatic lesions in the lumbar spine was scanned with medium-energy general-purpose (MEGP) and high-energy general-purpose (HEGP) collimators (basic study B). Ten patients with CRPC underwent SPECT imaging 2 h after Ra-223 injection successively with MEGP and HEGP collimators in random order for 30 min each. Lesion detectability and semi-quantitative analyses of bone metastasis (i.e. lesion-to-background ratio (LBR)) were performed compared to Tc-99m HMDP SPECT. Results Basic study A revealed that an 84-keV photopeak ± 20% using the HEGP collimator offers better SPECT image quality than the other imaging conditions. Basic study B showed that uptake in one of the spheres was overestimated by overlapped activity of the tube-shaped chamber in planar imaging whereas the spheres had similar counts and significantly higher sphere-to-background ratio in SPECT. On both planar and SPECT images, HEGP gave higher image contrast than MEGP (p

Симултано поткожно инјектирање на Ј-131 и Tc-99m во трасерски количини на стаорци, покажува во три случаи еднаков тиреоиден клиренс за двата радиоизотопа, но во два случаи се прикажува разлика.Клиренс студиите со Ј-131 и Tc-99m поради различната динамика на концентрација во раната „анорганска фаза“ во тиреоидеата, покажа дека не се изводливи. Најверојатно Tc-99m во тек на транспортот од поткожното ткиво до тироцитите претрпува промена во смисол на евентуална редукција, што може да ја промени динамиката на тироидниот аптејк.Подкожниот пат на администрација на Tc-99m не обезбедува еднакв клиренс на Ј-131 во тироидеата и за физиолошки студии Tc-99m може да даде погрешни резултати., Thyroid clearance of J-131 and Tc-99m after simultaneous subcutaneous injection in rats were estimated in the early phase. Arterial blood samples were drawn with a polyethene catheter inserted in the iliac artery in intervals of two minutes. The animals were sacrificed at the 20th minute and the wet weight of the thyroid gland was estimated. Tc-99m activity was counted on a ring counter consisting of GM tubes. The activity of J-131 was measured after the decay of Tc-99m. On and Tc-99m were identical which suggests that the subcutaneous way of Tc-99m application alters the pertechnetate state of the compound very similar to the oral route of Tc-99m pertechnetate application.

WOS: 000388115200003, Peptide radiopharmaceuticals have an increasing significance in nuclear medicine practice. beta-casomorphin is a digestive peptide with 6 amino acids (Tyr-Pro-Phe-Pro-Gly-Pro). N terminal amino acid chain mainly tyr-pro-phe-pro structured exogen opioid peptid type beta cosomorphin are beta-receptor agonistic activity with priority. Animal studies show that beta-casomorphins can act as opioid receptor agonists. The aim of this study was to label beta-casomorphin with (99m) Tc and to examine its usefulness as an opioid receptor binding radiopharmaceutical in Albino Wistar rats and cancer cells. beta-casomorphin was labeled with (99m) Tc radionuclide using bifunctional chelating agent. Quality control studies were done by Instant Thin layer chromatography (ITLC) and High performance liquid chromatography (HPLC) methods. Binding efficiency of the compound was more than 99%. It was observed as stable for at least 3 h at room temperature. Lipophilicity was also performed for labeled molecule. Imaging studies for (99m) Tc labeled molecule was done in rats by using gamma camera. For biodistribution studies; (99m) Tc labeled molecule was injected to the rats from tail vein and radioactivity per gr weight of each organ was measured as count per second (cps). Receptor specificity was evaluated in imaging and biodistribution studies in experimental animals. Cell labeling studies were also performed on breast and ovarien cancer cells. In terms of evaluating the biodistribution of (99m) Tc-beta-casomorphin molecule in rats, uterus and ovary displayed high involvement. It was also confirmed by cell labeling studies. If the radiopharmaceutical is radiolabeled with therapeutic radionuclides it would be useful for therapy for uterus, ovary and breast tumors., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TBAG-104T241], This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK), the author wish to thank TUBITAK for financial support (Grant No: TBAG-104T241).

A general procedure for the preparation of a new class of neutral six-coordinated mixed ligand [Tc-99m(III)(PS)(2)(Ln)] compounds (PS = trisalkyl-phosphino-thiolate; Ln = dithiocarbamate) is reported as well as their in vitro stability and the ex vivo tissue distribution studies. [Tc-99m(PS)(2)(Ln)] complexes were prepared in high yield in nearly physiologic conditions following a one-pot procedure. For instance, the chemical identity of [Tc-99m(PSiso)(2)(L1)] (PSiso = 2-(diisopropylphosphino)ethanethiol; L1 = pyrrolidine dithiocarbamate) was determined by HPLC comparison with the corresponding (99g)Tc-complex. All complexes comprise the stable [Tc-99m(III)(PS)(2)](+) moiety, where the remaining two coordination positions are saturated by a dithiocarbamate chelate, also carrying bioactive molecules (e.g., 2-methoxyphenylpiperazine). [Tc-99m(PS)(2)(Ln)] complexes were inert toward ligand exchange reactions. No significant in vitro and in vivo biotransformation were observed, underlining their remarkable thermodynamic stability and kinetic inertness. These results could be conveniently utilized to devise a novel class of Tc-99m(III)-based compounds useful in radiopharmaceutical applications.

Summary Background Although specificity of SPECT/CT examination using technetium-99m radiolabeled red blood cells (Tc-99m-RBC) for detection of liver hemangiomas is very high, it is still not perfect. It is possible to overlook a malignancy. Moreover, the difference in accumulation of RBCs between a hemangioma and uninvolved liver remains unknown. The aim of the study is to determine the quotients of accumulation of Tc-99m-RBC in hemangiomas and in normal liver parenchyma (HEM/liv), and to verify, whether the quotient could be potentially helpful in distinguishing hemangiomas from other RBC-accumulating liver masses. Material/Methods 34 liver lesions larger than 1.5 cm classified scintigraphically (qualitatively) in our Department as either typical or suspicious of hemangioma 1.5–4 years earlier were enrolled in this retrospective study. Their SPECT/CT images were acquired 1 hour after in vivo labeling of RBCs with Tc-99m. In reconstructed images, ellipsoidal regions of interest (ROIs) with diameters of about 1.5 cm were created in the assessed lesions (HEM) and in the uninvolved liver parenchyma (liv). The HEM/liv quotients were calculated for each mass. The results were compared with radiological data. Results 31 lesions were found to be clinically and radiologically typical for hemangiomas, their HEM/liv ratios were at least 1.6 (smaller masses) or 1.8 (larger masses). One lesion with HEM/liv ratio equal to 1.21 was classified as metastasis. Two lesions with HEM/liv 1.42 and 1.46 were classified as benign foci other than hemangioma. Conclusions The quantitative analysis can be preliminarily proposed as a helpful tool in the assessment of possible liver hemangiomas.

The Tc-99m-labelling of the amino acids tyrosine (Tyr) and lysine (Lys), fundamental building blocks of proteins and peptides, as well as biological properties of the labelled compounds are investigated. Three different approaches for the labelling with Tc-99m have been investigated: direct reduction with stannous tin in the presence of the amino acids, the preformed chelate approach through polydentate chelates DTPA and GH, and the organometallic approach using [Tc-99m(CO)(3)(H2O)(3)](+) precursor. The direct labelling approach was not successful and the yield was poor. In the presence of DTPA and GH, the labelling efficiency was between 43.6 and 97.8%, depending on the amino acid and the polydentate chelate. The use of [Tc-99m(CO)(3)(H2O)(3)](+) precursor point at the formation of Tc-99m(l) co-ordinated complexes with high yield. In this approach, pH and heating influenced the yields. The results of organ distribution study for [Tc-99m(Tyr)(H2O)(CO)(3)] and [Tc-99m(Lys)(H2O)(CO)(3)] show accumulation in liver, kidneys and intestine., Copyright (C) 2007 John Wiley and Sons, Ltd.

The nature of the heteroatom X incorporated in the five-member PXP-diphosphine spacer was found to play a primary unit role both in the stereochemical arrangement and overall stability of nitrido containing [M(N)(PXP)]2+ metal fragments (M = Tc, Re). Thus, by mixing PXP ligands with labile [Re(N)Cl4]- and [Tc(N)Cl2(PPh3)2] nitrido precursors in CH2Cl2/MeOH mixtures, a series of neutral [M(N)Cl2(PXP)] complexes (M = Tc, 1-5; M = Re, 8-9) was collected. In the resulting distorted octahedrons PXP adopted facial or meridional coordination, and combination with halide co-ligands produced three different stereochemical arrangements, i.e. fac,cis mer,cis and mer,trans, depending primarily on the nature of the diphosphine heteroatom X. When X = NH, mer,cis-[Tc(N)Cl2(PNP1)] 1 was the only isomer formed. Alternatively, when a tertiary amine nitrogen (X = NR; R = CH3, CH2CH2OCH3) was introduced in the spacer, fac,cis-[M(N)Cl2(PN(R)P)] complexes (M = Tc, 2, 3; M = Re, 8f) were obtained. Isomerization into the the mer,cis-[Re(N)Cl2(PN(R)P)], 8m, species was observed only in the case of rhenium when the tertiary amine group carried the less encumbering methyl substituent. Fac,cis-[Tc(N)Cl2(PSP)], 4f, was isolated in the solid state when X = S, but mixture of fac,cis-[Tc(N)Cl2(PSP)] and mer,trans-[Tc(N)Cl2(PSP)], 4m, isomers was found in equilibrium in the solution state. A similar equilibrium between fac,cis-[M(N)Cl2(POP)] (M = Tc, 5f; M = Re, 9f) and mer,trans-[M(N)Cl2(POP)] (M = Tc, 5m; M = Re, 9m) species was detected in POP containing complexes. The molecular structure of all of these complexes were assessed by means of conventional physico-chemical techniques including multinuclear NMR spectroscopy and X-ray diffraction analysis of representative mer,cis-[Tc(N)Cl2(PN(H)P)] 1, fac,cis-[Tc(N)Cl2(PSP)] 4f, and mer,cis-[Re(N)Cl2(PN(Me)P)] 8m compounds.

Isolated limb perfusion (ILP) therapy using a combination of tumour necrosis factor alpha (TNF) and cytostatic agents in hyperthermic conditions has proven to be effective in treating cancers limited to limbs or to a single organ such as the liver. A critical step for ILP is the accurate and real-time monitoring of that TNF toxic effects become relevant when overcoming the 10% limit of the 'effective' therapeutic dose administered during ILP. The most diffuse procedure for systemic leakage monitoring is based on the utilization of human soluble serum albumin (HSA) labelled with 131I and an external scintillation detector. In order to overcome some drawbacks connected with the properties of 131I, we developed a new procedure based on the utilization of HSA labelled with 99mTc in combination with a hand held gamma probe used as a detector. Our procedure consists of the following steps: (1) a 99mTc-HSA dose standardized as 0.5 MBq x kg(-1) body weight is injected into the ILP circuit before TNF administration; (2) a hand held gamma probe is placed over the pre-cordial area in a zone pre-marked on the patient's skin during a simulation test; (3) 48-72 h before ILP, a simulation test is obtained using a 99mTc-HSA dose corresponding to 10% of the dose calculated for ILP (i.e., 0.05 MBq x kg(-1) body weight); (4) during the simulation test the maximum count-rate zone detected on the pre-cordial area is marked on patient's skin; (5) a 60 min time-activity curve corresponding to the circulating 99mTc-HSA radioactivity effective decay is calculated and fitted; and (6) this time-activity curve is used to compensate for the leakage systemic counting observed during ILP. In order to compare the external, probe counting with the circulating radioactivity, in the first 10 patients from a total series of 43 treated patients, the results of external, probe monitoring were compared with the results of patient blood and perfusion circuit samples taken simultaneously every 5 min and measured by a laboratory gamma counter placed in the operating theatre. A good correlation was found between the two methods (R2 = 0.965, P0.01). It is concluded that the proposed procedure, based on the combination of 99mTc-HSA as the radiotracer and a hand held gamma probe as the detector, appears to be technically simple and accurate enough in the real-time monitoring of perfusion leakage in ILP cancer therapy. Moreover, using 99mTc-HSA as the radiotracer, the risk of radioactive contamination is significantly lower in comparison with 131I-HSA.

The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4− or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

Multimerization of peptides can improve the binding characteristics of the tracer by increasing local ligand concentration and decreasing dissociation kinetics. In this study, a new bombesin homodimer was developed based on an epsilon-aminocaproic acid-bombesin(7-14) (Aca-bombesin(7-14)) fragment, which has been studied for targeting the gastrin-releasing peptide receptor (GRPR) in prostate cancer. The bombesin homodimer was conjugated to 6-hydrazinopyridine-3-carboxylic acid (HYNIC) and labeled with Tc-99m for SPECT imaging. The in vitro binding affinity to GRPR, cell uptake, internalization and efflux kinetics of the radiolabeled bombesin dimer were investigated in the GRPR-expressing human prostate cancer cell line PC-3. Biodistribution and the GRPR-targeting potential were evaluated in PC-3 tumor-bearing athymic nude mice. When compared with the bombesin monomer, the binding affinity of the bombesin dimer is about ten times lower. However, the Tc-99m labeled bombesin dimer showed a three times higher cellular uptake at 4 h after incubation, but similar internalization and efflux characters in vitro. Tumor uptake and in vivo pharmacokinetics in PC-3 tumor-bearing mice were comparable. The tumor was visible on the dynamic images in the first hour and could be clearly distinguished from non-targeted tissues on the static images after 4 h. The GRPR-targeting ability of the Tc-99m labeled bombesin dimer was proven in vitro and in vivo. This bombesin homodimer provides a good starting point for further studies on enhancing the tumor targeting activity of bombesin multimers.

In this study 'second generation' AnxV was specifically labeled with Tc-99m in three different ways outside the binding region of the protein to obtain an improved target-to-background activity ratio. The compounds were tested in vitro and in vivo in normal mice and in a model of hepatic apoptosis (anti-Fas mAb). The apoptosis binding was most prominent for the HIS-tagged 'second generation' AnxV labeled with Tc-99m(CO)(3) in comparison to Tc-99m-HYNIC-cys-AnxV and Tc-99m(CO)(3)-DTPA-cys-AnxV. (C) 2009 Elsevier Ltd. All rights reserved. ispartof: Bioorganic & medicinal chemistry vol:18 issue:3 pages:1356-1363 ispartof: location:England status: published

Introduction: The aim of this study was to find out if Y-90 could form a stabile complex with meso-2,3-dimercaptosuccinic acid (DMSA) and if Y-90-DMSA may have potential for tumor therapy in the palliative treatment of bone metastases. Methods: The preparing of Y-90-DMSA was carried out by varying experimental parameters, such as ligand concentration, pH, time, and temperature of the reaction, in order to maximize the labeling yield. Analysis of the complexes enclosed the radiochemical quality control (instant thin-layer chromatography, paper chromatography, and high-performance liquid chromatography), determination of pharmacokinetical parameters as well as biodistrbution study in health male Wistar rats. In vitro stability of the complexes was tested too. Results: Y-90-DMSA could be prepared in high yields ( GT 95%) under optimized conditions of reaction. Stability studies in saline and human serum in vitro showed no significant release of activity from the ligand over 24 hours and 10 days, respectively. The preliminary biodistribution results in rat at 2 hours indicated that Y-90-DMSA, at both pH levels, was significantly retained into bone. The uptake in the kidneys was lower for Y-90-DMSA at pH 8.0 then at pH 3.0. The retention in other organs was negligible. Conclusions: Y-90 complexes could be made with ease with DMSA. Y-90-DMSA was obtained in good yield and was found to be very stable. A promising biodistribution result of this complex pointed at potential in the palliative treatment of bone metastases.

PubMedID: 9481503 A 7-year-old child who had previously undergone a left pyeloplasty because of vesicoureteral reflux (VUR) underwent dynamic Tc-99m-DTPA imaging for an evaluation of renal function. Dynamic images showed a nonfunctioning left kidney and a normally functioning right kidney with pelvicaliceal stasis. Following furosemide injection, the right pelvicaliceal stasis disappeared in a few minutes, while the left ureteral and subsequently left pelvicaliceal system was filling with the activity that came from the right kidney that had passed through the bladder. This drainage demonstrated a high degree VUR (Grade III) on the side of the nonfunctioning kidney. Extensive parenchymal damage was thought to be due to a high degree VUR in the left kidney. A static Tc-99m DMSA study and ultrasonography revealed the presence of left VUR nephropathy.

A 47-day-old female infant presented with congenital inguinal hernia, seizure on the 2(nd) day of life, fever, progressive jaundice, acholic stools and distension of abdomen. She was suspected to have choledochal cyst with extrahepatic biliary atresia (EHBA) and referred for an Hepatobiliary Tc-99m iminodiacetic acid (HIDA) scan. On HIDA scan, a functional diagnosis of ruptured choledochal cyst was made which was not possible on anatomical imaging like ultrasound (USG)/computed tomography (CT) scan. This was supported thereafter by bilious aspirate on abdominal paracentesis. Immediate laparotomy with T-tube insertion was done. The child improved dramatically after the procedure. Biliary peritonitis secondary to cyst perforation or rupture is a rare complication reported to occur in 1-2% cases of choledochal cyst. Early diagnosis and management is the key to reduce the morbidity and mortality.