Radiolabeled florescent-magnetic graphene oxide nanosheets: probing the biodistribution of a potential PET-MRI hybrid imaging agent for detection of fibrosarcoma tumor.

PURPOSE: Radiolabeled graphene oxide (GO) nanosheets has been one of the most extensively studied nanoplatform for in vivo radioisotope delivery. Herein, we describe the functionalization of the surface of GO nanosheets with Fe3O4 magnetic nanoparticles, cysteine amino acid as an interface ligand, and cadmium telluride quantum dots. MATERIALS AND METHODS: To enable In vivo PET imaging, the GO@Fe3O4-cys-CdTe QDs were labeled with 68Ga to yield [68Ga] Ga-Go@ Fe3O4-Cys-CdTe QDs. Furthermore, serum stability tests were performed and the biological behavior of the nanocomposite was evaluated in rats bearing fibrosarcoma tumor. RESULTS: Liver, blood and tumor were the most accumulated sites at 1 h after the injection, and the radiolabeled nanocomposite as a PET/MRI imaging agent showed fast depletion from body and acceptable tumor uptake. CONCLUSION: Magnetic (Fe3O4) and fluorescent components (CdTe QDs) along with a positron-emitting radionuclide will help to design a multimodal imaging system (PET/MRI/OI) which will offer the advantages of combined imaging techniques and further possible used in localized radionuclide therapy. Overall, [68Ga] Ga-GO@Fe3O4-cys-CdTe QDs nanocomposite shows great promise as a radiolabeled imaging agent owing to high accumulation in tumor region.

Preparation and quality control of a new porphyrin complex labeled with 45Ti for PET imaging.

This study aims to produce and quality control of a new porphyrin complex labeled with 45Ti for PET imaging, so at the first step, the cross-section of 45Sc(p,n)45Ti was investigated by TALYS-1.6 and the optimal target thickness and theoretical yield were calculated by SRIM code. The purified 45Ti was labeled with the anticancer agent of tetrakis (pentafluorophenyl) porphyrin (TFPP). The radiochemical purity and the percentage of labeling were evaluated by radiation layer chromatography then the division coefficient of [45Ti]-TFPP was calculated. The dual coincidence imaging system was used for imaging 1 and 2 h after injection [45Ti]-TFPP to rats. Immediately after imaging, the mean percent injected dose per gram and specific activity of different tissues including blood, heart, lungs, stomach, liver, bone, kidney, spleen, intestine, muscle, feces, and skin were measured. The yield of 45Ti production was measured 468 MBq/µAh and the labeling rate was observed more than 98%. The highest activity was observed in the liver (%ID/g = 2.27%, 1 h) and spleen (2.2%, 1 h), respectively, because of the high lipophilic of 45Ti-TFPP. SPECT images showed a significant uptake of radiopharmaceuticals in the abdomen. The labeling rate of 45Ti-TFPP was high and this compound has the potential for clinical application in different ways than PSMA, it can be joined with photodynamic therapy (Severin et al., 2015).

Synthesis of Magnetic Ions-Doped QDs Synthesized Via a Facial Aqueous Solution Method for Optical/MR Dual-Modality Imaging Applications.

This research reports the preparation and examination of Cadmium Telluride (CdTe) Quantum Dots and doping CdTe QDs with Europium (Eu), Gadolinium (Gd), and Manganese (Mn) prepared in aqueous solution using TGA as a capping agent. Magnetic QDs (MQDs) are important agents for fluorescence (FL) /magnetic resonance (MR) dual-modal imaging due to their excellent optical and magnetic properties. Herein, the chemical bonds, structural, fluorescence, and magnetized properties of CdTe QDs and effect of Mn, Eu, and Gd ions doping on their properties were examined by X-ray powder diffraction (XRD), high-resolution transmission electron microscopy (HRTM), Energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared spectroscopy (FTIR), photoluminescence spectroscopy (PL), Ultraviolet-visible spectroscopy (UV-Vis), and vibrating sample magnetometer measurements (VSM). Almost similar X-Ray patterns with the absence/presence of ions for all samples with cubic crystal structures were obtained which indicated that the introduction of ions into CdTe QDs could not alter the cubic primary structure of CdTe. Monodisperse size distributed with seemingly-spherical shapes, and also, the estimated mean diameters about 3 and less than 3 nm of QDs were obtained. The effect of X ions injection on the fluorescence and UV-Vis properties of the QDs were also investigated. Optical studies showed the decreases in bandgap as the heating time increases during synthesis while undergoing red-shift. The CdTe nanocrystals with high PL quantum yields were achieved in more than 6 h of heating. Also, investigations have shown the quenching of fluorescence by the existence of ions in the CdTe QDs. Then, all the ions doped QDs exhibited ferromagnetic behavior at room temperature by a vibrating sample magnetometer which confirmed the success of the presentation of ions into CdTe cubic crystal structure. They can have been employed as a suitable contrast agent successfully for biological applications such as FL/MR dual-modal imaging.

Grafting of [(64)Cu]-TPPF20 porphyrin complex on Functionalized nano-porous MCM-41 silica as a potential cancer imaging agent.

Mesoporous silica, MCM-41, functionalized with 3-aminopropyltriethoxysilane (APTES) was investigated as a potential drug delivery system, using [(64)Cu]-5, 10, 15, 20-tetrakis penta fluorophenyl porphyrin complex. [(64)Cu]-TPPF20 complex was grafted on functionalized MCM-41. The product was characterized by paper chromatography, FTIR spectroscopy, low angle X-ray diffraction, CHN and TGA/DTA analyses and atomic force microscopy. The biological evaluations of the grafted complex, [(64)Cu]-TPPF20@NH2-MCM-41, were done in Fibrosarcoma tumor-bearing Sprague-Dawley rats using scarification studies and Sopha DST-XL Dual-Head SPECT system. The actual loading amount of aminopropyl groups was found about 1.6mmol per gram of final silica. The specific activity of the final compound was found to be 3Ci/g. Amine functionalized MCM-41 was found to be a good platform for theranostic radiopharmaceuticals such as copper-64 complexes. Considering the accumulation of the tracer in tumor cells, fast wash-out from normal tissues, the short half-life copper-64 and less imposed radiation doses to patients, [(64)Cu]-TPPF20@NH2-MCM-41 can potentially be a suitable candidate for tumor imaging applications and future PET studies.

Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent / Produção, controle de qualidade, avaliação de biodistribuição e avaliação da dose preliminar de [177Lu] -tetra complexo fenil porfirina como um possível agente terapêutico

Due to interesting therapeutic properties of ¹⁷⁷Lu and tumor avidity of tetraphenyl porphyrins (TPPs), ¹⁷⁷Lu-tetraphenyl porphyrin was developed as a possible therapeutic compound. ¹⁷⁷Lu of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu₂O₃sample with thermal neutron flux of 4 × 10¹³ n.cm^-2.s^-1. Tetraphenyl porphyrin was synthetized and labeled with ¹⁷⁷Lu. Radiochemical purity of the complex was studied using Instant thin layer chromatography (ITLC) method. Stability of the complex was checked in final formulation and human serum for 48 h. The biodistribution of the labeled compound in vital organs of wild-type rats was studied up to 7 d. The absorbed dose of each human organ was calculated by medical internal radiation dose (MIRD) method. A detailed comparative pharmacokinetic study was performed for ¹⁷⁷Lu cation and [¹⁷⁷Lu]-TPP. The complex was prepared with a radiochemical purity: >97±1% and specific activity: 970-1000 MBq/mmol. Biodistribution data and dosimetric results showed that all tissues receive approximately an insignificant absorbed dose due to rapid excretion of the complex through the urinary tract. [¹⁷⁷Lu]-TPP can be an interesting tumor targeting agent due to low liver uptake and very low absorbed dose of approximately 0.036 to the total body of human...

Devido às propriedades interessantes do ¹⁷⁷Lu e da avidez tumoral das tetrafenil porfirinas (TPP), desenvolveu-se a ¹⁷⁷Lu-tetrafenil porfirina como composto terapêutico potencial. ¹⁷⁷Lu de atividade específica de 2,6-3 GBq/mg foi obtido por irradiação de amostra de Lu₂O₃ com fluxo térmico de nêutrons de 4 × 10¹³ n.cm^-2.s^-1. Sintetizou-se a tetrafenil porfirina e marcou-se com ¹⁷⁷Lu. A pureza radioquímica do complexo foi estudada usando método de Cromatografia Instantânea de Camada Delgada ( ITLC). A estabilidade do complexo foi checada na formulação final e no ser humano por 48 h. A biodistribuição do composto marcado em órgãos vitais de ratos do tipo selvagem foi estudada por mais de 7 dias. A dose absorvida para cada órgão humano foi calculada pelo método da Dose Médica de Radiação Interna (MIRD). Estudo farmacocinético comparativo detalhado foi efetuado para o cátion ¹⁷⁷Lu e para o [¹⁷⁷Lu]-TPP. O complexo foi preparado com pureza radioquímica >97±1% e atividade específica de 970-1000 MBq/mmol. Os dados de biodistribuição e os resultados dosimétricos mostraram que todos os tecidos receberam uma dose absorvida aproximadamente insignificante devido à rápida excreção do complexo pelo trato urinário. O [¹⁷⁷Lu]-TPP pode ser um agente interessante de direcionamento do tumor devido à baixa captação pelo fígado e pela dose bem baixa absorvida, de, aproximadamente, 0,036 do corpo humano total...

Structural and spectroscopic characterizations of tetra-nuclear niobium(V) complexes of quinolinol derivatives.

Reactions between niobium ethoxide and 8-hydroxy-2-methylquinoline or 5-chloro-8-hydroxyquinoline have been explored. Two new tetranuclear heteroleptic niobium complexes containing oxo, ethoxo, and quinolinate chelate rings have been synthesized and characterized by (1)H, (13)C and (93)Nb NMR, UV-Vis, and FT-IR spectroscopies, and single-crystal X-ray diffraction. The molecular structures of the niobium complexes, [Nb4(µ-O)4(µ-OEt)2(ONC10H8)2(OEt)8] (I) and [Nb4(µ-O)4(µ-OEt)2(ONC9H5Cl)2(OEt)8] (II), are composed of a pair of edge-sharing bioctahedral moieties in which connected via two almost linear oxo-bridges, with a large difference in the NbO distances. Single-crystal structures showed both complexes are centrosymmetric and contain two distinct Nb centers, and results confirmed by observation of two niobium signals in the (93)Nb NMR spectra of complexes.

In vivo SPECT imaging of tumors by 198,199Au-labeled graphene oxide nanostructures.

Graphene oxide (GO) sheets functionalized by aminopropylsilyl groups (8.0 wt.%) were labeled by (198,199)Au nanoparticle radioisotopes (obtained through reduction of HAuCl4 in sodium citrate solution followed by thermal neutron irradiation) for fast in vivo targeting and SPECT imaging (high purity germanium-spectrometry) of tumors. Using instant thin layer chromatography method, the physicochemical properties of the amino-functionalized GO sheets labeled by (198,199)Au NPs ((198,199)Au@AF-GO) were found to be highly stable enough in organic phases, e.g. a human serum, to be reliably used in bioapplications. In vivo biodistribution of the (198,199)Au@AF-GO composite was investigated in rats bearing fibrosarcoma tumor after various post-injection periods of time. The (198,199)Au@AF-GO nanostructure exhibited a rapid as well as high tumor uptake (with uptake ratio of tumor to muscle of 167 after 4h intravenous injection) that resulted in an efficient tumor targeting/imaging. Meantime, the low lipophilicity of the (198,199)Au@AF-GO caused to its fast excretion (~24 h) throughout the body by the kidneys (as also confirmed by the urinary tract). Because of the short half-life of (198,199)Au radioisotopes, the (198,199)Au@AF-GO with an excellent tumor targeting/imaging and fast washing out from the body can be suggested as one of the most effective and promising nanomaterials in nanotechnology-based cancer diagnosis and therapy.

Synthesis, characterization and in vivo evaluation of [(62)Zn]-benzo-δ-sultam complex as a possible pet imaging agent.

OBJECTIVE: The development of a new tracer based on the cyclic sulfonamides (sultams) was investigated. METHODS: 3-(Methoxy-phenyl-methyl)-1,6-dimethyl-1H benzo[c][1,2] thiazine 2,2-dioxide (benzo-δ-sultam) was synthesized and characterized by elemental analysis, FT-IR spectroscopy and single crystal X-ray structure determination. The prepared cyclic sulfonamide was labeled with non-commercial (62)Zn radioisotope for fast in vivo targeting and Coincidence imaging purposes (radiochemical purity 97 % ITLC, 96 % HPLC, specific activity 20-23 GBq/mmol). In vivo biodistribution of the final complex was investigated in Sprague Dawley(®) rats bearing fibro sarcoma tumor after 2, 4 and 8 h post injection and compared with free Zn(+2) cation. RESULTS: Using instant paper chromatography method, the physicochemical properties of labeled compounds were found sufficiently stable in organic phases, e.g. a human serum, to be reliably used in bioapplications. CONCLUSIONS: The complex exhibited a rapid as well as high tumor uptake (tumor to blood ratio 4.38 and tumor to muscle ratio 9.63) resulting in an efficient tumor targeting agent.

Synthesis and Evaluation of [(67)Ga]-AMD3100: A Novel Imaging Agent for Targeting the Chemokine Receptor CXCR4.

In order to develop a possible C-X-C chemokine receptor type 4 (CXCR4) imaging agent for oncological scintigraphy, [(67)Ga]-labeled 1,1'-[1,4-Phenylene-bis(methylene)]bis(1,4,8,11-tetraazacyclotetradecane) ([(67)Ga]-AMD3100) was prepared by using [(67)Ga]GaCl3 and AMD-3100 for 2 h at 50 °C (radiochemical purity: >95% ITLC, >99% HPLC, specific activity: 1800-2000 TBq/mmol) in acetate buffer. The stability of the complex was checked in the presence of human serum (37 °C) and in the final formulation for four days. The biodistribution of the labeled compound in the vital organs of wild type Sprague-Dawley rats was determined and compared with that of the free Ga(3+) cation up to 48 h. Considering the spleen as the target organ, the best target:non target ratios were obtained 48 h post-injection (spleen:blood ratio; 14.5 and spleen:muscle ratio; 88.4). Initial SPECT images and biodistribution results in the wild type rats matched each other and demonstrated rapid washout of the tracer from the urinary tract. SPECT images in human breast carcinoma-bearing mice demonstrated a detectable tumor uptake in 48 h post-injection.

Radiosynthesis and Quality Control of [(67)Ga]-3,4-dimethoxylated Porphyrin Complex as a Possible Imaging agent.

Radiolabeled porphyrins are potential tumor avid radiopharmaceuticals because of their impersonation in the human body, ability to complex various radionuclides, water solubility, low toxicity etc. In this work a radiogallium porphyrin complex has been developed. [(67)Ga] labeled 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin ([(67)Ga]-TDMPP) was prepared using freshly prepared [(67)Ga]GaCl3 and 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (H2TDMPP) for 60 min at 100°C. Stability of the complex was checked in final formulation and human serum for 24 h, followed by biodistribution and imaging studies in wild type rats up to 24 h. The radiocomplex was obtained with radiochemical purity >99% (ITLC) and >98% (HPLC), specific activity: 12-15 GBq/mmol. The partition coefficient was determined (log P=1.63). A detailed comparative pharmacokinetic study performed for (67)Ga cation and [(67)Ga]-TDMPP. The complex was mostly washed out from the circulation through kidneys. Myocardial uptake was significantly observed by SPECT and biodistribution studies. Knee and shoulder joints demonstrated significant activity uptake in 2h post injection. Higher water solubility of the complex due to ionic nature of the complex is an advantage for rapid wash-out of the complex from the system, the complex has significant joint uptake compared to other radiolabeled porphyrins which the mechanisms are explained.

Synthesis and characterization of 8-hydroxyquinoline complexes of tin(IV) and their application in organic light emitting diode.

A series of 8-hydroxyquinoline complexes of tin, Q(2)SnCl(2) (Q = 2-methyl-8-hydroxyquinoline, 8-hydroxyquinoline, 5,7-dibromo-8-hydroxyquinoline, 5-chloro-8-hydroxyquinoline, 5,7-dichloro-8-hydroxyquinoline and 5-nitro-8-hydroxyquinoline) were prepared by reacting stannous dichloride with 8-hydroxyquinoline and its derivatives. All complexes were characterized by elemental analysis, mass spectrometry and infrared, UV-vis and (1)H NMR spectroscopes. Furthermore, the molecular structure of a representative complex, dichlorido-bis(5-nitro-quinolin-8-olato-2N,O)tin(IV), was determined by single-crystal X-ray diffraction. The photoluminescence (PL) properties of all prepared compounds and electroluminescence (EL) property of a selected complex (Q = 5-chloro-8-hydroxyquinoline) were investigated. The results showed that the emission wavelength can be tuned by electron donating or withdrawing group substituent on 8-hydroxyquinoline. Application of prepared complexes in fabrication of an OLED has been demonstrated.

Development of a (68)Ga-Fluorinated Porphyrin Complex as a Possible PET Imaging Agent.

AIM: Due to the interesting pharmacologic properties of porphyrins, the idea of developing a possible tumor imaging agent using PET by incorporating (68)Ga into a suitable porphyrin ligand was investigated. METHODS: (68)Ga-labeled 5,10,15,20-tetrakis(pentafluoro-13 phenyl) porphyrin ((68)Ga-TFPP) was prepared using freshly eluted [(68)Ga]GaCl3 obtained from a 68Ge/68Ga generator developed in-house and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (H2TFPP) for 60 min at 100°C. RESULTS: The complex was prepared with high radiochemical purity (>99% ITLC, >99% HPLC, specific activity: 13-14 GBq/mmol). Stability of the complex was checked in the final formulation and in human serum for 5 h. The partition coefficient was calculated for the compound (log P = 0.62). The biodistribution of the labeled compound in vital organs of Swiss mice bearing fibrosarcoma tumors was studied using scarification studies and SPECT imaging up to 1 h. The complex was mostly washed out from the circulation through kidneys and liver. The tumor-to-muscle ratio 1 h post injection was 5.13. CONCLUSION: The radiolabeled porphyrin complex demonstrated potential for further imaging studies in other tumor models.

Development of ga-67 maltolate complex as an imaging agent.

Due to the antitumor activity of Gallium MAL complex, as well as recent findings on new targeted biomolecules in malignant cells through this complex, the development of radiolabeled gallium complex for future imaging studies was targeted. Ga-67 labeled 3-hydroxy-2-methyl-4H-pyran-4-onate (Ga-67 MAL) was prepared using freshly prepared Ga-67 chloride and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form in 25 min at 40° C. The stability of the complex was checked in final formulation and human serum for 24 h followed by the administration in Swiss mice for biodistribution studies. The complex was prepared in high radiochemical purity (> 97% ITLC, > 98% HPLC) and specific activity of 13-14 GBq/mmol and was stable in the presence of serum for 48 h. The partition coefficient was calculated for the compound (log p = 0.40). A detailed comparative pharmacokinetic study was performed for Ga-67 cation and Ga-67-MAL. The complex is more rapidly washed out from the circulation through kidneys and liver compared to Ga-67 cation and can be an interesting tumor imaging agent due to the fact that the cold compound is undergoing clinical trials as a safe and potential therapeutic agent for cancer.

Grafting of a novel gold(III) complex on nanoporous MCM-41 and evaluation of its toxicity in Saccharomyces cerevisiae.

The goal of this research was to investigate the potential of newly synthesized gold complex trichloro(2,4,6-trimethylpyridine)Au(III) as an anticancer agent. The gold(III) complex was synthesized and grafted on nanoporous silica, MCM-41, to produce AuCl(3)@PF-MCM- 41 (AuCl(3) grafted on pyridine-functionalized MCM-41). The toxicity of trichloro(2,4,6- trimethylpyridine)Au(III) and AuCl(3)@PF-MCM-41 in Saccharomyces cerevisiae (as a model system) was studied. The gold(III) complex showed a mid cytotoxic effect on yeast viability. Using the drug delivery system, nanoporous MCM-41, the gold(III) complex became a strong inhibitor for growth of yeast cells at a very low concentration. Furthermore, the animal tests revealed a high uptake of AuCl(3)@PF-MCM-41 in tumor cells. The stability of the compound was confirmed in human serum.

Grafting aluminum(III) 8-hydroxyquinoline derivatives on MCM-41 mesoporous silica for tuning of the light emitting color.

Fluorescent materials (Q)(3-n)(2-BuO)(n)Al (Q = 8-hydroxyquinoline, 2-methyl-8-hydroxyquinoline and 5-chloro-8-hydroxyquinoline, n = 1 or n = 2) were prepared in toluene by reacting aluminum 2-butoxide with 8-hydroxyquinoline and its derivatives. The compounds were characterized by (1)H, (13)C and (27)Al NMR in solution, and the coordination status of the aluminum atom in the complexes were determined by (27)Al NMR chemical shifts. The compounds were grafted on mesoporous silica (MCM-41) at room temperature without isolation of the complexes. The prepared materials were characterized by elemental analysis, FT-IR spectroscopy, low-angle X-ray diffraction (XRD), thermal analysis (TGA/DSC) and N(2) adsorption and desorption measurements. The results showed that the characteristic mesoporous structure of MCM-41 after grafting aluminum complexes remains intact. The photoluminescence (PL) properties of (Q)(3-n)(2-BuO)(n-1)@Al-MCM-41 were investigated. The results revealed that the maximum wavelength is modulated by the MCM-41 guest.

Pyridine-functionalized MCM-41 as an efficient and recoverable catalyst for the synthesis of pyran annulated heterocyclic systems.

Pyridine-functionalized MCM-41 catalyzed reactions between tetracyanoethylene and various activated CH-acid compounds are described. These reactions afford the corresponding pyran annulated heterocyclic ring systems in high yields at room temperature within a few minutes. The work-up procedure is very simple and the products do not require further purification. The catalyst can be recycled and reused for several times without observable loss of performance.

Bis(µ-2-methyl-8-oxidoquinolin-1-ium-κO:O)bis-[(acetato-κO,O')(2-methyl-8-oxidoquinolin-1-ium-κO)bis-(nitrato-κO,O')lanthanum(III)].

The N-heterocycles in the centrosymmetric title compound, [La(2)(C(10)H(9)NO)(4)(CH(3)COO)(2)(NO(3))(4)], exist in the zwitterionic form. One heterocycle binds to a metal center whereas the other bridges two metal centers. Each La atom is chelated by an acetate and two nitrate groups and is surrounded by nine O atoms in a distorted tricapped trigonal-prismatic coordination environment. The N-H groups form intra-molecular N-H⋯O hydrogen bonds. One of the nitrate ions is disordered over two positions in a 0.80 (3):0.20 (3) occupancy ratio.

Bis(tribenzyl-ammonium) tetra-chloridoaurate(III) chloride.

In the title compound, (C(21)H(22)N)(2)[AuCl(4)]Cl, the Au(III) atom adopts a square-planar coordination geometry defined by four chloride ions. In the crystal structure, inter-molecular N-H⋯Cl hydrogen bonds link the organic cations and the uncoordinated chloride ion.

Di-µ-ethano-lato-bis-[diethano-lato(2-methyl-quinolin-8-olato)titanium(IV)].

In the centrosymmetric dinuclear title compound, [Ti(2)(C(10)H(8)NO)(2)(C(2)H(5)O)(6)], the Ti atom is bonded to an N,O-bidentate quinolin-8-olate ligand, two terminal ethano-late anions and two bridging ethano-late anions in a distorted TiNO(5) octa-hedral geometry. An intra-molecular C-H⋯O hydrogen bond occurs; in the crystal, inter-molecular C-H⋯O inter-actions help to establish the packing.

1'-Methyl-2-oxo-5'-phenyl-spiro-[indoline-3,3'-pyrrolidine]-4',4'-dicarbo-nitrile.

The title spiro-compound, C(20)H(16)N(4)O, crystallizes with four independent mol-ecules in the asymmetric unit. In all of them, the oxindole unit is planar, the r.m.s. deviations ranging from 0.07 to 0.08 Å, while the pyrrolinyl ring adopts an envelope conformation (with the N atom representing the flap). In the crystal, adjacent mol-ecules are linked by N-H⋯N and N-H⋯O hydrogen bonds.