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The extensive development of radiopharmaceuticals towards early tumour detection and treatment has increased the demand for new ligands with higher tumour selectivity. Research has been done on the potential of the novel O,O′-diethylethylenediamine-N,N′-di-3-propanoate () ligand as a radionuclide vehicle for tumour targeting. Under alkaline conditions, hydrolyses and produces half ester ligand () and diacid ligand (), with characteristic donor atom array N,N,O. Ligand was successfully labelled with 99mTc at pH = 9 by coordination with the octahedral fac-[99mTc(CO)3(H2O)3]+ intermediate, forming the main radioproduct fac-[99mTcL′(CO)3] (Tc1). The 99mTc complex showed a low lipophilic character (log P = 0.48) and low binding affinity to human serum albumin (2.51 ± 0.48%). In vitro stability studies in saline and human plasma, as well as challenge studies with cysteine and histidine, revealed high stability of the complex during 24 h. Biodistribution studies of Tc1 in female C57BL/6 mice bearing B16/F1 melanoma metastases showed significant tumour uptake: 9.81 ± 1.19%ID g−1 in the liver, 5.87 ± 0.54%ID g−1 in the lungs and 3.17 ± 0.33%ID g−1 in the ovary at 30 min post-injection. Favourable physicochemical properties, satisfactory in vitro/in vivo stability and biodistribution profile in the experimental metastatic melanoma model indicate the possible application of the radiolabelled ligand in tumour diagnosis. Copyright © 2015 John Wiley & Sons, Ltd.

Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their effi- ciency as radioactive vectors, Fe3O4-Naked (80 6 5 nm) and polyethylene glycol 600 diacid functionalized Fe3O4 (Fe3O4- PEG600) MNPs (46 6 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe3O4-PEG600 MNPs was 200 W/g, indi- cated their potential in hyperthermia based cancer treat- ments. The labeling yield, in vitro stability and in vivo biodistribution profile of 90 Y-MNPs were compared. Both types of MNPs were 90 Y-labeled in reproducible high yield (>97%). The stability of the obtained radioactive nanopar- ticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The bio- distribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for 90 Y-Fe3O4-Naked MNPs and 19.61%ID/g for 90 Y-Fe3O4-PEG600 MNPs) whereas

Two novel diamine dioxime ligands, 4,7-diaza-3,8-diethyldecane-2,9-dione bis oxime (3) and 4,9-diaza-3,10-diethyldodecane-2,11-dione bis oxime (5), were synthesized in order to develop new brain perfusion imaging agents, based on 99mTc(V)-complexes. The synthesis involved condensation of 2-hydroxyimino-3-pentanone with appropriate diamine in protic solvent which afforded the bis imine adducts. Subsequent reduction of imine functional groups yielded a diastereoisomeric mixture of 3 and 5. UV–visible, IR, 1H NMR, 13C NMR and elemental analysis were used to characterize the structures of the synthesized compounds. 99mTc-complexes of both diamine dioximes were prepared and radiolabeling conditions optimized to give the maximum yield. Physicochemical parameters of the labeled complexes as well as and their biodistribution in rats were investigated. Both compounds (3 and 5) formed 99mTc-complexes with a net charge of zero, determined by electrophoresis. The resultant lipophilic 99mTc-complexes of 3 and 5 were readily formed at pH ~9.0 within 10 min at room temperature with yields of 90% and 95%, respectively. The 99mTc-3 complex was found to be stable within 1 h, while 99mTc-5 was stable for a few hours. A significant brain uptake of 99mTc-3 (2.1% injected dose) and 99mTc-5 (1.8% injected dose) complexes, 2 min after injection, is in accordance with their lipophilicity. The present study suggests that both ligands are promising candidates as new 99mTc-based brain-imaging agents. Copyright © 2012 John Wiley & Sons, Ltd.

Two rhenium(I) tricarbonyl complexes with the tridentate monoanionic NSO ligands, 4-(benzimidazol-2-yl)-3-thiabutanoic acid (complex 3) and [1-(11-carboxyundecanyl)-4-(benzimidazol-2-yl)]-3-thiabutanoic acid (complex 4) were synthesized and characterized by spectroscopic methods and elemental analysis. X-ray crystallographic analysis of complex 3 revealed a distorted octahedral geometry around rhenium defined by the three facially bound CO groups and the NSO donor atom set of the tridentate ligand. The analogous technetium-99m complexes (complexes 5 and 6) were also prepared quantitatively by reaction of the NSO ligands with the fac-[Tc-99m(H2O)(3)(CO)(3)](+) synthon and their identity was established by chromatographic comparison to their rhenium congeners. Biodistribution in mice of complex 6 bearing the fatty acid chain showed significant heart uptake (6.26 +/- 0.79% ID/g p.i.) at 1 min accompanied, however, with a heart: blood ratio below 1. (C) 2011 Elsevier B. V. All rights reserved.

Two rhenium(l) tricarbonyl complexes, with the monoanionic tridentate NSO type ligand, 4-(imidazolin-2-yl)-3-thiabutanoic acid and 4-(N-ethylimidazolin-2-yl)-3-thiabutanoic acid were synthesized and isolated in pure form. Both complexes were characterized by spectroscopic methods and elemental analysis. The solid-state structure of 4-(imidazolin-2-yl)-3-thiabutanoic acid and of both complexes was established by X-ray crystallography. The geometry about the rhenium is octahedral. The analogous technetium-99m complexes were also prepared quantitatively by the reaction of both ligands with the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) synthon and their identity was established by chromatographic comparison to their rhenium congeners. (C) 2009 Elsevier Ltd. All rights reserved.

The goal of this investigation was to examine the possibilities for yttrium-90-labeling of the 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), which is currently labeled with technetium-99m and as a Tc-99m-DPD clinically used as bone imaging agent. Analysis of the complex enclosed the radiochemical quality control methods, biodistribution studies, as well as the determination of pharmacokinetic parameters. The biological behavior of complexes Y-90-DPD, Tc-99m-DPD and Y-90-labeled DPD-kit formulation [Y-90-(Sn)-DPD] in animal model was compared. The labeling conditions were standardized to give the maximum yield, which ranged between 93% and 98%. The examined Y-90 complex could be easily prepared, with an outstanding yield and was also found to be very stable for at least 10 h after Y-90-labeling. Protein binding value was 4.6 +/- 0.7% for Y-90-DPD complex and the complex possess a hydrophilic character. The satisfactory results of Y-90- DPD biodistribution in healthy test animals were obtained; the uptake in the bone was 11-13% ID/g after 24 h depending on the pH value during the preparation. With high skeletal uptake, a minimum uptake in soft tissues and rapid blood clearance the Y-90-DPD complex proved to be an excellent candidate for targeting tumor therapy. (C) 2008 Elsevier Ltd. All rights reserved.

Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their efficiency as radioactive vectors, Fe₃O₄-Naked (80 ± 5 nm) and polyethylene glycol 600 diacid functionalized Fe₃O₄(Fe₃O₄-PEG600) MNPs (46 ± 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe₃O₄-PEG600 MNPs was 200 W/g, indicated their potential in hyperthermia based cancer treatments. The labeling yield, in vitro stability and in vivo biodistribution profile of (90) Y-MNPs were compared. Both types of MNPs were (90)Y-labeled in reproducible high yield (97%). The stability of the obtained radioactive nanoparticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The biodistribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for (90)Y-Fe₃O₄-Naked MNPs and 19.61%ID/g for (90)Y-Fe₃O₄-PEG600 MNPs) whereas minor fractions attained in other organs. The main difference between the two types of MNPs was the higher accumulation of (90)Y-Fe₃O₄-Naked MNPs in the lungs (12.14%ID/g vs. 2.00%ID/g for (90)Y-Fe₃O₄-PEG600 MNPs) due to their in vivo agglomeration. The studied radiolabeled magnetic complexes such as (90)Y-Fe₃O₄-PEG600 MNPs constitute a great promise for multiple diagnostic-therapeutic uses combining, for example, MRI-magnetic hyperthermia and regional radiotherapy.

Radio labeled albumin microspheres with encapsulated citric acid-coated magnetite nanoparticles were developed as a targeting approach to localize both radioactivity and magnetic energy at the tumor site. We present in vitro and in vivo studies of yttrium-90 (Y-90)-labeled human scrum albumin magnetic microspheres (HSAMMS) as a multifunctional agent for possible applications in a bimodal radionuclide-hyperthermia cancer therapy. The HSAMMS were produced using a modified emulsification-heat stabilization technique and contained 11 nm magnetite nanoparticles coated with citric acid, distributed as inhomogeneous clusters within the albumin microspheres. The size, size distribution and the morphology of magnetite nanoparticles and HSAMMS were determined by FESEM, HRTEM and SEM/FIB dual beam. The average particle size of the complete HSAMMS was 20 mu m, and they exhibited superparamagnetic behavior at room temperature. The in vitro experiments (in saline and human serum) revealed the high stability of the labeled HSAMMS in saline and human serum after 72 h. Following the intravenous administration of the Y-90-HSAMMS in rats, 88.81% of the activity localizes in the lungs after 1 h, with 82.67% remaining after 72 h. These data on Y-90-HSAMMS provide good evidence for their potential use in bimodal radionuclide-hyperthermia cancer therapy.

The present study describes for the first time a procedure for the radiolabeling of fullerene (C(60)) nanocrystals (nanoC(60)) with Na (125)I, as well as the biodistribution of radiolabeled nanoC(60) ((125)I-nanoC(60)). The solvent exchange method with tetrahydrofuran was used to make colloidal water suspensions of radiolabeled nanoC(60) particles. The radiolabeling procedure with the addition of Na (125)I to tetrahydrofuran during dissolution of C(60) gave a higher radiochemical yield of radiolabeled nanoC(60) particles in comparison to the second option, in which Na (125)I was added after C(60) was dissolved. Using photon correlation spectroscopy and transmission electron microscopy, (125)I-nanoC(60) particles were found to have a crystalline structure and a mean diameter of 200-250 nm. The (125)I-nanoC(60) had a particularly high affinity for human serum albumin, displaying 95% binding efficiency after 1 h. Biodistribution studies of (125)I-nanoC(60) in rats indicated significant differences in tissue accumulation of (125)I-nanoC(60) and the radioactive tracer Na (125)I. The higher accumulation of radiolabeled nanoC(60) was observed in liver and spleen, while accumulation in thyroid, stomach, lungs and intestines was significantly lower in comparison to Na (125)I. In addition to being useful for testing the biological distribution of nanoC(60), the described radiolabeling procedure might have possible applications in cancer radiotherapy.

Colloidal particle size is an important characteristic to consider when choosing a radiopharmaceutical for diagnosis and therapeutic purposes in nuclear medicine. Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) were used to determine the particle-size distribution of (90)Y- and (99m)Tc-labelled antimony trisulfide (Sb(2)S(3)) and tin colloids (Sn-colloid). (90)Y-Sb(2)S(3) and (99m)Tc-Sb(2)S(3) were found to have a diameter of 28.92 +/- 0.14 and 35.61 +/- 0.11 nm, respectively, by PCS. By TEM, (90)Y-Sb(2)S(3) particles were measured to be 14.33 +/- 0.09 nm. (90)Y-labelled Sn colloid were found to exist with a d(v(max1)) of 805 nm and a d(v(max2)) of 2590 nm, by PCS, whereas (99m)Tc-Sn colloid was shown to have more than 80% of radioactive particles of approximately 910 nm by PCS. For (90)Y-labelled Sb(2)S(3) and Sn colloid, a comparison of TEM and PCS indicates that these techniques found significantly different mean diameters. TEM has an excellent resolution necessary for radiocolloid particle-sizing analysis, and it is a desirable size-measuring technique because it is more reliable than PCS.