Tricarbonyl Core Research Articles

Plasma Rhenium and Selenium Concentrations After Repeated Daily Oral Administration of Rhenium(I)-diselenoether in 4T1 Breast Tumor-bearing Mice.

Rhenium(I)-diselenoether (Re-diSe) is a compound combining a rhenium tricarbonyl(I) core with a diselenide ligand. A high dose of 60 mg/kg had a pro-tumor effect in a previous study, in non-immune deficient 4T1 tumor-bearing mice, while doses of 1 and 10 mg/kg did not affect tumor growth, after repeated oral administrations. This study aimed to examine the tumor effects of a lower dose of 0.1 mg/kg with the same experimental design and to assay plasma Re and Se concentrations. Syngenic BALB/cByJ (JAX) mice were orthotopically inoculated with 4T1 mammary breast cancer cells. Re-diSe was daily administered orally for 23 days at doses of 0.1, 1, and 10 mg/kg, whereas controls received no treatment. Tumor and mice weights were measured at the end of the experiment. Plasma Re and Se concentrations were assayed by an inductively coupled plasma sector field mass spectrometry instrument (ICP-sf-MS). The weight of the tumors did not vary in treated versus non-treated mice. The limit of detection (LOD) of Re was 0.34 nmol/l. Plasma Re concentrations were 14±20 nmol/l at doses of 0.1 mg/kg, and increased at higher doses, up to 792±167 nmol/l at doses of 10 mg/kg. Plasma Se concentrations were significantly increased in mice treated with the dose of 0.1 mg/kg (4,262±1,511 nmol/l) versus controls (1,262±888 nmol/l), but not from 0.1 to 1 mg/kg, nor from 1 to 10 mg/kg. The 0.1 mg/kg dose of Re-diSe resulted in detectable plasma Re concentrations and significantly increased plasma Se concentrations. In the future, doses as low as 0.1 mg/kg of Re-diSe will be tested, exploring its potential immune interest as a metronomic schedule of treatment, but in mouse models that readily develop extensive metastatic disease.

Preparation, biological evaluation and radiolabeling of [99mTc]-technetium tricarbonyl procainamide as a tracer for heart imaging in mice

Abstract This study focuses on the synthesis and preliminary bio-evaluation of [99mTc]-technetium tricarbonyl procainamide ([99mTc]-technetium tricarbony PA) as a viable cardiac imaging agent. The compound, [99mTc]-technetium tricarbony PA, was synthesized by labelling procainamide with a [99mTc]-technetium tricarbonyl core, yielding a high radiochemical yield and radiochemical purity of 98%. Under optimal circumstances, high radiochemical yield and purity were obtained utilizing [99mTc]-technetium tricarbonyl core within 30 min of incubation at pH 9, 200 µg substrate concentration, and 100 °C reaction temperature. The heart showed a high absorption of 32.39 ± 0.88% of the injected dose/g organ (ID/g), confirming the suitability of [99mTc]-technetium tricarbonyl PA as a viable complex for heart imaging.

Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core.

The traceless Staudinger ligation with its two variants is a powerful biorthogonal conjugation method not only for the connection of biomolecules, but also for the introduction of fluorescence- or radiolabels under mild reaction conditions. Herein, the strategic evaluation of the traceless Staudinger ligation for radiolabeling 99mTc using the fac-[Tc(CO)3]+ core is presented. A convenient and high-yielding three-step synthetic procedure of dipicolylamine-based phosphanols as ligands for the mild radiolabeling was developed. The labeling was accomplished using a tricarbonyl kit and a 99mTc-pertechnetate generator eluate showing 87% radiochemical conversion. The respective rhenium-based, non-radioactive reference compounds were synthesized using (Et4N)2[Re(CO)3Br3] as precursor. All products were analyzed by NMR, MS, and elemental analysis. Additional XRD analyses were performed.

Tc(OH2)(CO)3(PPh3)2]+: A Synthon for Tc(I) Complexes and Its Reactions with Neutral Ligands.

A scalable synthesis of the novel and highly reactive [Tc(OH2)(CO)3(PPh3)2]+ cation is described. The ligand-exchange chemistry of this compound with neutral ligands coordinating through C, N, O, S, Se, and Te has been explored systematically. The complexes either retain the original mer-trans tricarbonyl core under exclusive exchange of the aqua ligand or form dicarbonyl complexes by thermal decarbonylation. Ligand exchange reactions starting from [Tc(OH2)(CO)3(PPh3)2]+ proceed under mild conditions and are generally almost quantitative. Some of the formed complexes are remarkably stable and inert, while others provide products with one labile ligand for further reactions. The derived complexes of the type [Tc(L)(CO)3(PPh3)2]+ and [Tc(L)2(CO)2(PPh3)2]+ represent an interesting opportunity for the development of 99mTc complexes with potential use in radiopharmacy. The ready displacement of the aqua ligand highlights the synthetic value of [Tc(OH2)(CO)3(PPh3)2]+ as a reactive entry point for further studies in the little explored field of the organometallic chemistry of technetium.

Re-188-tricarbonyl tamoxifen as a theranostic radiopharmaceutical for estrogen receptor expressing breast cancers: radiolabeling, characterization and in-vitro cytotoxic assessment.

Development of a novel theranostic radiopharmaceutical for estrogen receptor, expressing unresectable primary and metastatic breast cancers. Tamoxifen was radiolabeled with Rhenium-188 (Re-188) through tricarbonyl core. Radiolabeled complex was characterized by 1proton nuclear magnetic resonance spectroscopy and Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF). Various quality control tests such as sterility, apyrogenicity, and radiochemical purity (RCP) were performed to assess the suitability of the radiopharmaceutical for intravenous administration. In-vitro cell culture studies were performed for cytotoxic assessment. In addition to this, exposure due to different doses of Re-188-tricarbonyl tamoxifen was also calculated. Re-188-tricarbonyl and Re-188-tricarbonyl tamoxifen showed more than 99% RCP. Sample was found to be sterile and pyrogens levels were within the permissible limit. Re-188-tricarbonyl tamoxifen was successfully characterized by MALDI-TOF and 1H-NMR spectroscopy. Re-188 (1.480 MBq) and tamoxifen (0.027 or 0.054 µM) individually showed 36 and 70% cell death, respectively. However, radiolabeled complex (Re-188-tricarbonyl tamoxifen) with the same amount of radioactivity (1.480 MBq) increased the cell death to more than 90% with one-fifth to one-tenth molar concentration of tamoxifen (0.0054 μM). Re-188-tricarbonyl tamoxifen can be synthesized in-house in radiopharmacy lab. Radionuclide therapy with Re-188-tricarbonyl tamoxifen can be given using 10 times less amount of tamoxifen as compared to cold tamoxifen.

Design of 99mTc radiolabeled gemcitabine polymeric nanoparticles as drug delivery system and in vivo evaluation

The main objective of this study is to create a multifunctional drug carrier system as a prototype product. For this purpose, Gemcitabine that used as an anticancer agent for several kinds of tumour therapy, and technetium(I)-tricarbonyl core, [99mTc(CO)3]+, was incorporated to the polymeric structure.In the current study PLA-PEG-COOH (polylactic acid-polyethylene glycol-carboxyl) copolymer was synthesized and the structure analysis was performed by FT-IR and 1H NMR. The surface charge, size and morphology of the polymeric nanoparticles was evaluated by Zeta Potential (ZP) analysis, Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM) methods. Gemcitabine loaded polymeric nanoparticles were radiolabeled with [99mTc(CO)3(H2O)3]+ and quality controls were performed by thin layer radiochromatograpy (TLRC) and high performance liquid radiochromatograpy (HPLRC). PLA-PEG-GEM complex was labeled with [99mTc(CO)3]+ in high radiochemical yield and purity. The radiolabeled complex is stable during the study period in saline solution. The biological activity of this radiolabeled system was evaluated performing biodistribution and gamma camera imaging on Wistar Albino rats which exhibited higher uptake in the lung and liver at all selected time points.

Design of docetaxel-loaded polymeric nanoparticles: characterization, radiolabeling with 99mTc and in vitro evaluation

This research aims to develop a polymeric drug delivery system for docetaxel (DTX) and to investigate its radiotracer potential by in vitro. DTX loaded Poly(lactic acid)/Poly(ethylene glycol) diblock copolymer (PLA–PEG) was synthesized and radiolabeled with technetium-99m tricarbonyl core. PLA–PEG–DTX nanoparticles had a particle size and zeta potential 120 ± 7.3 nm and − 24.66 ± 1.5 mV respectively, which was further supported by SEM image. The radiolabeling efficiency of 99mTc(CO)3-PLA–PEG–DTX was found to be 90 ± 3.51%,. In vitro study was carried out on cancer cell lines (MCF7, MDA-MB-231) to examine the biological behavior of docetaxel loaded PLA–PEG nanoparticles.

Biocompatible Delivery System for Metformin: Characterization, Radiolabeling and In Vitro Studies.

In recent years, the uses of nanotechnology in medicine have an increasing potential as an effective nanocarrier system. These systems are improved with the purpose of maximizing therapeutic activity and minimizing undesirable side-effects. Moreover, radiolabeled nanoparticles can be used as agents for diagnosis and therapeutic purposes in clinical applications. They have three main components: the core, the targeting biomolecule, and the radionuclide. It is aimed to synthesize Metformin (MET) loaded Solid Lipid Nanoparticles (MET-SLN) and radiolabeled with technetium-99m tricarbonyl core. The structure of synthesized nanoparticles was characterized by Fourier Transform Infrared Spectroscopy (FTIR). The particle size and morphology of nanoparticles were examined by Dynamic Light Scattering (DLS), and Scanning Electron Microscope (SEM). Quality control studies of radiolabeled MET-SLN [99mTc(CO)3-MET-SLN] were performed by High-Performance Liquid Radiochromatography (HPLRC) and Thin Layer Radiochromatography (TLRC). The radiolabeling yield of [99mTc(CO)3-MET-SLN] was found to be 88%. In vitro studies have been performed on cancer lines(MCF7, MDA-MD-231 breast, and HEPG2 liver cancer cells) to determine the biological behavior of 99mTc(CO)3-MET-SLNs. The results showed that higher uptake values were observed on estrogen-positive MCF7 breast cancer cell line according to estrogen negative MDA-MB-231 breast cancer and HEPG2 liver cancer cell lines.

Exploring the In Vivo and In Vitro Anticancer Activity of Rhenium Isonitrile Complexes.

The established platinum-based drugs form covalent DNA adducts to elicit their cytotoxic response. Although they are widely employed, these agents cause toxic side-effects and are susceptible to cancer-resistance mechanisms. To overcome these limitations, alternative metal complexes containing the rhenium(I) tricarbonyl core have been explored as anticancer agents. Based on a previous study ( Chem. Eur. J. 2019, 25, 9206), a series of highly active tricarbonyl rhenium isonitrile polypyridyl (TRIP) complexes of the general formula fac-[Re(CO)3(NN)(ICN)]+, where NN is a chelating diimine and ICN is an isonitrile ligand, that induce endoplasmic reticulum (ER) stress via activation of the unfolded protein response (UPR) pathway are investigated. A total of 11 of these TRIP complexes were synthesized, modifying both the equatorial polypyridyl and axial isonitrile ligands. Complexes with more electron-donating equatorial ligands were found to have greater anticancer activity, whereas the axial ICN ligands had a smaller effect on their overall potency. All 11 TRIP derivatives trigger a similar phenotype that is characterized by their abilities to induce ER stress and activate the UPR. Lastly, we explored the in vivo efficacy of one of the most potent complexes, fac-[Re(CO)3(dmphen)(ptolICN)]+ (TRIP-1a), where dmphen = 2,9-dimethyl-1,10-phenanthroline and ptolICN = para-tolyl isonitrile, in mice. The 99mTc congener of TRIP-1a was synthesized, and its biodistribution in BALB/c mice was investigated in comparison to the parent Re complex. The results illustrate that both complexes have similar biodistribution patterns, suggesting that 99mTc analogues of these TRIP complexes can be used as diagnostic partner agents. The in vivo antitumor activity of TRIP-1a was then investigated in NSG mice bearing A2780 ovarian cancer xenografts. When administered at a dose of 20 mg/kg twice weekly, this complex was able to inhibit tumor growth and prolong mouse survival by 150% compared to the vehicle control cohort.

Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of 99mTc-Tricarbonyl-Based Radiopharmaceuticals.

The organometallic technetium-99m tricarbonyl core, [99mTc][Tc(CO)3(H2O)3]+, is a versatile precursor for the development of radiotracers for single photon emission computed tomography (SPECT). A drawback of the 99mTc-tricarbonyl core is its lipophilicity, which can influence the pharmacokinetic properties of the SPECT imaging probe. Addition of polar pharmacological modifiers to 99mTc-tricarbonyl conjugates holds the promise to counteract this effect and provide tumor-targeting radiopharmaceuticals with improved hydrophilicities, e.g., resulting in a favorable fast renal excretion in vivo. We applied the “Click-to-Chelate” strategy for the assembly of a novel 99mTc-tricarbonyl labeled conjugate made of the tumor-targeting, modified bombesin binding sequence [Nle14]BBN(7–14) and the carbohydrate sorbitol as a polar modifier. The 99mTc-radiopeptide was evaluated in vitro with PC-3 cells and in Fox-1nu mice bearing PC-3 xenografts including a direct comparison with a reference conjugate lacking the sorbitol moiety. The glycated 99mTc-tricarbonyl peptide conjugate exhibited an increased hydrophilicity as well as a retained affinity toward the Gastrin releasing peptide receptor and cell internalization properties. However, there was no significant difference in vivo in terms of pharmacokinetic properties. In particular, the rate and route of excretion was unaltered in comparison to the more lipophilic reference compound. This could be attributed to the intrinsic properties of the peptide and/or its metabolites. We report a novel glycated (sorbitol-containing) alkyne substrate for the “Click-to-Chelate” methodology, which is potentially of general applicability for the development of 99mTc-tricarbonyl based radiotracers displaying an enhanced hydrophilicity.

Robust Binding of Disulfide-Substituted Rhenium Bipyridyl Complexes for CO2 Reduction on Gold Electrodes.

Heterogenization of homogenous catalysts on electrode surfaces provides a valuable approach for characterization of catalytic processes in operando conditions using surface selective spectroelectrochemistry methods. Ligand design plays a central role in the attachment mode and the resulting functionality of the heterogenized catalyst as determined by the orientation of the catalyst relative to the surface and the nature of specific interactions that modulate the redox properties under the heterogeneous electrode conditions. Here, we introduce new [Re(L)(CO)3Cl] catalysts for CO2 reduction with sulfur-based anchoring groups on a bipyridyl ligand, where L = 3,3′-disulfide-2,2′-bipyridine (SSbpy) and 3,3′-thio-2,2′-bipyridine (Sbpy). Spectroscopic and electrochemical analysis complemented by computational modeling at the density functional theory level identify the complex [Re(SSbpy)(CO)3Cl] as a multi-electron acceptor that combines the redox properties of both the rhenium tricarbonyl core and the disulfide functional group on the bipyridyl ligand. The first reduction at −0.85 V (vs. SCE) involves a two-electron process that breaks the disulfide bond, activating it for surface attachment. The heterogenized complex exhibits robust anchoring on gold surfaces, as probed by vibrational sum-frequency generation (SFG) spectroscopy. The binding configuration is normal to the surface, exposing the active site to the CO2 substrate in solution. The attachment mode is thus particularly suitable for electrocatalytic CO2 reduction.

Rhenium and technetium-complexed silicon rhodamines as near-infrared imaging probes for bimodal SPECT- and optical imaging.

Fluorescent Si-rhodamines were modified to enable complexation with the Re(i)- and 99mTc(i)-tricarbonyl core. The corresponding complexes exhibit suitable properties as bimodal imaging probes for SPECT- and optical imaging in vitro. Importantly, the novel in- aqueous-solution-stable, functionalized Si-rhodamines retain favourable optical properties after complexation (QY = 0.09, λabs = 654 nm, λem = 669 nm in PBS) and show promising near-infrared optical properties for potential in vivo applications enabling bimodal scintigraphic imaging and optical imaging, e.g. used in radio- and fluorescence-guided tumour resection.

Bioevaluation of 99mTc(I) carbonyl-radiolabeled amino acid coated magnetic nanoparticles in vivo

In this paper, amino acid coated and radiolabeled magnetic nanoparticles (MNPs) were prepared as a potential diagnostic agent. Magnetic nanoparticles were synthesized and functionalized by l-alanine and l-cysteine amino acids in one step. Besides surface functionalization, amino acid coating also provided favourable particle size. Structural characterization was performed by scanning electron microscopy. We obtained 30–38 nm and 22–30 nm diameter ranges with spherical shape for l-alanine and l-cysteine coated nanoparticles, separately. Then l-alanine and l-cysteine coated MNPs were radiolabeled with 99mTc(I)-tricarbonyl core (99mTc(CO)3-Alanine-MNP, 99mTc(CO)3-Cysteine-MNP) with a labeling yield of 63 ± 3% and 74 ± 2%. Pure radiolabeled magnetic particles were obtained by washing them with saline solution, and the radiochemical purity of 99mTc(CO)3-Alanine-MNP and 99mTc(CO)3-Cysteine-MNP were found as 94.3 ± 0.47% and 97.6 ± 1.06% in each of the final solution, respectively. In addition, both radiolabeled nanoparticles were stabile up to 4 h at 37 °C temperature in vitro conditions.After radiolabeling with 99m-Technetium tricarbonyl core, biological behaviour of nanoparticles was evaluated for each in vivo on male Wistar Albino rats.

Correction: Substituted bidentate and ancillary ligands modulate the bioimaging properties of the classical Re(i) tricarbonyl core with yeasts and bacteria

Correction for ‘Substituted bidentate and ancillary ligands modulate the bioimaging properties of the classical Re(i) tricarbonyl core with yeasts and bacteria’ by Alexander Carreño et al., New J. Chem., 2017, 41, 2140–2147.

Substituted bidentate and ancillary ligands modulate the bioimaging properties of the classical Re(i) tricarbonyl core with yeasts and bacteria

Six classical rhenium(i) tricarbonyl complexes were investigated for their ability to be used as dyes for bioimaging in walled cells.

Activation of the manganese(I) tricarbonyl core by selective variation of bidentate ligands (L,L'-Bid = N,N' and N,O donor atom sets) in fac-[Mn(CO)3(L,L'-Bid)(CH3OH)](n) complexes.

A range of fac-[Mn(CO)3(L,L'-Bid)(H2O)](n) (L,L'-Bid = neutral or monoanionic bidentate ligands with varied L,L' donor atoms, N,N' and N,O, 1,10-phenanthroline, 2,2'-bipyridine, 2-picolinate, 2,4-quinolinate; n = 0, +1) has been synthesized and the methanol substitution has been investigated for the first time. The complexes were characterized by UV/vis, IR and NMR spectroscopy and X-ray crystallographic studies of the compounds fac-[Mn(CO)3(Bipy)(H2O)][CF3SO3] () and fac-[Mn(CO)3(Phen)(H2O)][CF3SO3] () are reported. A two order-of-magnitude of activation for the methanol substitution is induced as manifested by the second order rate constants with (N,N'-Bid) < (N,O-Bid). Forward and reverse rate and stability constants from slow and stopped-flow UV/vis measurements (k1, M(-1) s(-1); k-1, s(-1); K1, M(-1)) for pyridine as entering nucleophile are as follows: fac-[Mn(CO)3(Phen)(CH3OH)](+) (2.39 ± 5) × 10(-3), (1.5 ± 0.3) × 10(-5), 159 ± 32; fac-[Mn(CO)3(2,4-QuinH)(CH3OH)] (4.5 ± 0.2), (4 ± 1) × 10(-2), 113 ± 29. Activation parameters (ΔH, kJ mol(-1); ΔS, J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as indicated are as follows: fac-[Mn(CO)3(Phen)(CH3OH)](+) (bromide ions) 66.7 ± 0.6, -27 ± 2; (pyridine) 80 ± 3, -25 ± 11; fac-[Mn(CO)3(Pico)(CH3OH)] (bromide ions) 68 ± 2, -24 ± 5. A dissociative interchange mechanism is proposed.

Preliminary in vitro and in vivo evaluation of liposomal nanoparticles for passive and active tumour targeting by scintigraphic and MRI imaging.

Liposomes belong to the most desirable drug delivery systems that enable their application in MRI and SPECT by incorporating lipids chelated to MR contrast agents as well as to radioactive tracers. Here we report our observation on a novel αvβ3- targeting liposome formulation (RGD-LP) and on the corresponding non-targeting control (NT-LP) for diagnosis and molecular imaging of tumor by exploiting SPECT/MRI technology. Radiolabelling was performed with 99mTc tricarbonyl core via the ligand cysteine (Cys). Both peptide and ligand were coupled to DSPE-PEG2000-Mal lipid. Radiochemical purity and in vitro stability tested in the presence of competitive ligands for 99mTc(I) were assessed by paper chromatography. For nuclear imaging a custom SPECT system (1.5mm spatial resolution) was used and the results were correlated to the biodistribution data. Both liposomes disposed of a PEG surface density of 5.5% and were loaded with 25% of Gd-based lipid (B2286) for MRI studies. For recording MR images, cells were transferred into glass capillaries, centrifuged and placed in an agar phantom. MR images were acquired on a Bruker Avance300 spectrometer operating at 7.1 T. In vivo MRI experiments were carried out on U87MG tumor xenografts with a 1T scanner (Bruker, Icon Instrument). Radiolabelling yield (>80%), radiochemical purity (>90%), in vitro stability in the presence of excess amount of cysteine and in 10% FBS/DMEM were satisfactory to permit in vivo evaluation at normal mice. NT-LP-Cys showed higher blood retention and lower uptake at liver and spleen at later time points than RGD-LP which is in good correlation with the in vivo MRI results obtained in U87MG bearing mice. The internalization amount of Gd3+ inside the cells was of higher extent for RGD-LP at all the time points analyzed. These results could be considered as an important step in the development of tumour targeted SPECT/MRI contrast agents for cancer imaging.

99mTc(CO)3(NTA) and 131I-OIH: Comparable Plasma Clearances in Patients with Chronic Kidney Disease

The pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)3-nitrilotriacetic acid ((99m)Tc(CO)3(NTA)) in rats and subjects with normal renal function are comparable to those of (131)I-o-iodohippuran ((131)I-OIH), the radiopharmaceutical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in subjects with renal failure. (99m)Tc(CO)3(NTA) was prepared with commercially available NTA and a commercially available labeling kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2.0 mCi) of (99m)Tc(CO)3(NTA) were coinjected with approximately 11.1 MBq (300 μCi) of (131)I-OIH in 8 subjects with stage 3-4 renal failure; simultaneous images were obtained for 24 min, followed by an anterior image over the gallbladder and abdomen. Plasma clearances were determined from 10 blood samples obtained 3-180 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. There was no difference in the plasma clearances of (99m)Tc(CO)3(NTA) and (131)I-OIH (177 ± 63 vs. 171 ± 66 mL/min/1.73 m(2), respectively) (P = 0.41). The plasma protein binding and red cell uptake of (99m)Tc(CO)3(NTA) were 35% ± 7% and 6% ± 3%, respectively; both values were significantly lower than the plasma protein binding (71% ± 5%) and red cell uptake (16% ± 2%) of (131)I-OIH (P < 0.001). There was no significant difference in the percentage injected dose in the urine at 30 min (P = 0.24) and at 3 h (P = 0.82); for comparison, the percentage dose in the urine at 3 h was 77% ± 9% for (99m)Tc(CO)3(NTA) and 78% ± 11% for (131)I-OIH. Image quality with (99m)Tc(CO)3(NTA) was excellent and no activity was identified in the gallbladder or intestine. Results in patients with renal failure show the clearance and rate of urine excretion of (99m)Tc(CO)3(NTA) to be equivalent to that of (131)I-OIH.

Thymidine kinase enzyme selective imaging radiopharmaceutical: 99mTc(CO)3-Ganciclovir

Abstract The aim of this study is to radiolabel ganciclovir, known as having selective antiviral properties against thymidine kinase, with technetium tricarbonylcore (99mTc(CO)3 +) and to investigate the biological behavior of this complex in vitro and in vivo. Commercially provided Ganciclovir (GCV) was radiolabeled with 99mTc(CO)3 +. Initially, optimum radiolabeling conditions were determined by analyzing factors such as temperature, pH and time. Quality control of the radiolabeled compound was performed. The radiolabeling yield was found to be 97%. The 99mTc(CO)3-GCV complex also displayed good in vitro stability during the 24 h period. In vitro cell uptake studies showed that the 99mTc(CO)3-GCV complex is highly uptaken in A-549, PC-3, HeLa cell lines according to the control group 99mTc(I)-tricarbonyl core. The knowledge gained from in vivo and in vitro studies of 99mTc(CO)3-GCV could contribute to the development of a new HSV1-tk gene imaging agent.

Preparation and characterization of radiolabeled magnetic nanoparticles as an imaging agent

Magnetic nanoparticles were prepared by a reduction–precipitation method and coated with an amino silane coupling agent. Guanine (Gua) was conjugated to the magnetic nanoparticles (MNPs) using glutaraldehyde as a cross-linker. Common techniques (Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and vibrating electron microscopy) were used to assess the properties of the particles. Structural investigations showed that amino silane-coated MNPs had a particle size of about 40–60 nm in diameter with a spherical morphology. The guanine-conjugated MNPs were radiolabeled with 99mTc(I)-tricarbonyl core (99mTc(CO)3-MNP-Gua) with a labeling yield of 72 ± 4 %. Pure radiolabeled magnetic particles were obtained by washing them with saline solution, and the radiochemical purity of 99mTc(CO)3-MNP-Gua was 98 ± 2 % in the final solution. The biologic distribution of guanine MNPs was assessed in New Zealand rabbits using a gamma camera. In the in vivo experiment, a high level of radioactivity was observed in the lungs and liver soon after intravenous administration of 99mTc(CO)3-MNP-Gua.