Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents.

Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L(+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO)5 and fac-[NEt4]2[ReBr3(CO)3] were used for the preparation of the Re complexes fac-[Re(NNO)(CO)3] (5a) and fac-[Re(SNO)(CO)3] (7a) which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the fac-[99mTc(CO)3]+ core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the fac-[99mTc][Tc(OH2)3(CO)3]+ precursor. The radiolabeled complexes were characterized by comparative HPLC analysis with the analogous rhenium (Re) complexes as references. In vitro studies in the A431 cell lines showed that both ligands and Re complexes inhibit A431 cell growth. Complex 5a demonstrated the highest potency (IC50 = 8.85 ± 2.62 µM) and was further assessed for its capacity to inhibit EGFR autophosphorylation, presenting an IC50 value of 26.11 nM. Biodistribution studies of the 99mTc complexes in healthy mice showed high in vivo stability for both complexes and fast blood and soft tissue clearance with excretion occurring via the hepatobiliary system.

Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds.

The presence of positron emission tomography (PET) centers at most major hospitals worldwide, along with the improvement of PET scanner sensitivity and the introduction of total body PET systems, has increased the interest in the PET tracer development using the short-lived radionuclides carbon-11. In the last few decades, methodological improvements and fully automated modules have allowed the development of carbon-11 tracers for clinical use. Radiolabeling natural compounds with carbon-11 by substituting one of the backbone carbons with the radionuclide has provided important information on the biochemistry of the authentic compounds and increased the understanding of their in vivo behavior in healthy and diseased states. The number of endogenous and natural compounds essential for human life is staggering, ranging from simple alcohols to vitamins and peptides. This review collates all the carbon-11 radiolabeled endogenous and natural exogenous compounds synthesised to date, including essential information on their radiochemistry methodologies and preclinical and clinical studies in healthy subjects.

Translation, Adaptation and Validation of the Pandemic Fatigue Scale (PFS) in the Greek Language.

The growing fatigue of citizens due to the COVID-19 pandemic has already been addressed and its results are visible and threatens citizen compliance. The aim of this study was to translate and validate the Pandemic Fatigue Scale (PFS) in the Greek language. A cross-sectional study was conducted between October 2021 to March 2022. The translation and cultural adaptation process was developed according to the research protocols among the university student population in Cyprus and tested the psychometric properties of PFS. Three hundred thirty-four subjects participated in the study through a web survey, which included general information and the study process. The internal consistency for the total PFS showed good reliability (six items, a = 0.88). A weak statistically significant positive correlation was found between the PFS and the Greek versions of Generalised Anxiety Disorder Assessment­GAD-7 (r = 0.1.96; p < 0.001) and the PFS and Patient Health Questionnaire­PHQ-9 (r = 0.173; p = 0.002) demonstrating good concurrent validity. Recovering from the pandemic, it is necessary to build systems to detect and respond to future healthcare crises. The results suggest that the psychometric properties of the Greek PFS are satisfactory. The measure of pandemic fatigue allows for identifying fatigue groups for targeted interventions and testing how pandemic fatigue might be reduced in such situations.

Synthesis and preclinical evaluation of rhenium and technetium-99m "4 + 1" mixed-ligand complexes bearing quinazoline derivatives as potential EGFR imaging agents.

Epidermal growth factor receptors (EGFR) of tyrosine kinase (TK) have shown high expression levels in most cancers and are considered a promising target for cancer diagnosis and therapy. Expanding the investigation for novel targeted radiopharmaceuticals, an EGFR inhibitor such as 4-aminoquinazoline derivatives along with a radionuclide such as technetium-99m (99mTc) could be ideal. Thus, we report herein the synthesis, characterization, and biological evaluation of new "4 + 1" mixed-ligand ReIII- and 99mTcIII-complexes of the general formula [99mTc][Tc(NS3)(CN-R)] bearing tris(2-mercaptoethyl)-amine (NS3) as the tetradentate tripodal ligand and a series of isocyanide derivatives (CN-R) of tyrosine kinase inhibitor (3-bromophenyl)quinazoline-4,6-diamine as the monodentate ligand. The quinazoline isocyanide derivatives 4a-d were prepared in two steps and reacted with the [Re(NS3)PMe2Ph] precursor leading to the final complexes 5a-d in high yield. All compounds were characterized by elemental analysis, IR, and NMR spectroscopies. In vitro studies, for their potency to inhibit the cell growth, using intact A431 cells indicate that the quinazoline derivatives 4a-d and the Re complexes 5a-d significantly inhibit the A431 cell growth. In addition, the EGFR autophosphorylation study of complex 5b shows an IC50 value in the nanomolar range. The corresponding "4 + 1" 99mTc-complexes 6a-d were prepared by employing the [99mTc]TcEDTA intermediate and the appropriate monodentate 4a-d in a two-step synthetic procedure with a radiochemical yield (RCY) from 63 to 77 % and a radiochemical purity (RCP) > 99 % after HPLC purification. Their structures have been established by HPLC comparative studies using the well-characterized Re-complexes 5a-d as reference. All 99mTc-complexes remain stable for at least 6 h, and their logD7.4 values confirmed their anticipated lipophilic character. Biodistribution studies in healthy Swiss albino mice of 99mTc-complexes showed hepatobiliary excretion and initial fast blood clearance. Complex 6b was also tested in Albino SCID mice bearing A431 tumors and showed rapid tumor uptake at 5 min (2.80 % ID/g) with a moderate tumor/muscle ratio (2.06) at 4 h p.i. The results encourage further investigation for this type of 99mTc-complexes as single-photon emission computed tomography (SPECT) radio agents for imaging tumors overexpressing EGFR.

Synthesis and Characterization of Novel [2 + 1] Tricarbonyl Rhenium Complexes with the Hydrophilic Phosphine Ligands PTA and CAP.

In the pursuit of hydrophilic model fac-[Re(CO)3]+ complexes for (radio) pharmaceutical applications, six novel [2 + 1] mixed-ligand complexes of the general type fac-[Re(CO)3(bid)P] were synthesized and characterized, where bid is a bidentate ligand bearing either (N, O) or (S, S') donor atom sets and P is the hydrophilic phosphine 1,3,5-triaza-7-phosphoadamantane (PTA) or its macrocyclic homologue 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane (CAP). The (N, O) ligands used in this study were picolinic and quinaldic acid, while the (S, S') ligand was diethyldithiocarbamate. The complexes were synthesized in generally high yields and purity and the characterization was performed by spectroscopic methods, IR, NMR, and elemental analysis. Detailed X-ray crystallographic study of molecular packing by using Hirshfeld analysis tools revealed a plethora of intermolecular interactions such as hydrogen bond, π⋯π, C-H⋯π, and carbonyl-carbonyl interactions. To our knowledge, the CAP complexes reported herein are the first example of [2 + 1] mixed-ligand fac-[Re(CO)3]+ complexes with CAP. The new complexes might have the potential to serve as platforms for the design of target-specific complexes with favorable pharmacokinetics.

Effective Labeling of Amine Pharmacophores through the Employment of 2,3-Pyrazinedicarboxylic Anhydride and the Generation of fac-[M(CO)3(PyA)P] and cis-trans-[M(CO)2(PyA)P2] Complexes (PyA = Pyrazine-2-carboxylate, P = Phosphine, M = Re, 99mTc).

The fac-[M(CO)3(PyA)(P)] and cis-trans-[M(CO)2(PyA)(P)2] neutral complexes (M is Re or 99mTc), based on the mixed ligand strategy with pyrazine-2-carboxylic acid (PyAH) as the bidentate N,O and triphenylphosphine as the monodentate P ligand, are presented. Through the employment of the anhydride of pyrazine-2,3-dicarboxylic acid (PyDA), the PyAH scaffold was conveniently derivatized with the model bioactive amine 1-(2-methoxyphenyl)piperazine, the active part of the 5-HT1A antagonist WAY100635. Reaction of either PyAH or the pharmacophore-bearing PyAH ligand (L1H) with fac-[M(CO)3]+ core in water yielded the intermediate fac-[M(CO)3(PyA)(H2O)] complexes. The labile aqua ligand was easily replaced by PPh3 to yield the fac-[Re(CO)3(PyA)(PPh3)] complexes, while in toluene under reflux, the cis-trans-[Re(CO)2(PyA)(PPh3)2] complexes were obtained. The latter complexes were alternatively obtained from mer-[Re(CO)3(PPh3)2Cl] by refluxing with the PyA ligand in toluene. The analogous 99mTc complexes were synthesized quantitatively, showing excellent stability in competition studies. The methodology described herein represents a practical procedure for the effective integration of the fac-[M(CO)3]+ core with amine-bearing biologically active compounds for diagnosis/therapy.

Synthesis and evaluation of new mixed "2 + 1" Re, 99mTc and 186Re tricarbonyl dithiocarbamate complexes with different monodentate ligands.

A series of "2 + 1" mixed ligand tricarbonyl complexes of the general formula fac-[Re/99mTc/186Re(CO)3(DDTC)(L)] containing diethyldithiocarbamate (DDTC) as a monoanionic bidentate ligand and a series of monodentate ligands L was synthesized, characterized and evaluated. The impact of ligand L on the radiochemical yield (RCY) and biodistribution of the final compounds was also investigated. DDTC and the appropriate L ligand [cyclohexyl isocyanide (cisc), tert-butyl isocyanide (tbi), triphenylphosphine (PPh3), methyldiphenylphosphine (PPh2Me), triphenylarsine (AsPh3), imidazole (im), and 4-aminopyridine (4AP)] readily reacted in equimolar amounts with the [Et4N]2[Re(CO)3Br3] precursor to afford fac-[Re(CO)3(DDTC)(cisc)], Re1, fac-[Re(CO)3(DDTC)(tbi)], Re2, fac-[Re(CO)3(DDTC)(PPh3)], Re3, fac-[Re(CO)3(DDTC)(PPh2Me)], Re4, fac-[Re(CO)3(DDTC)(AsPh3)], Re5, fac-[Re(CO)3(DDTC)(im)], Re6 and fac-[Re(CO)3(DDTC)(4AP)], Re7, complexes in high yields (>80%). All Re complexes were fully characterized by IR, NMR, and in addition Re4, Re5, and Re7 with X-ray crystallography. Analogous reactions as performed with Re were subsequently explored on the 99mTc and 186Re-tracer levels using the corresponding fac-[99mTc/186Re(CO)3(H2O)3]+ precursor. Complexes 99mTc1 - 99mTc5, 186Re1 and 186Re3 were obtained in high radiochemical yield (>91%), while the complexes 99mTc6, 99mTc7 and 186Re7 formed with radiochemical yields of 55%, 28%, and 75%, respectively. The 99mTc and 186Re-complexes were characterized by comparative HPLC analysis using the analogous Re complexes. During histidine and cysteine challenge experiments at 37 °C through 6 h, complexes 99mTc1 - 99mTc5 remained > 92% stable, while complexes 99mTc6 and 99mTc7 remained only 8% stable through 3 h. Similar studies for 186Re-complexes showed that 186Re1 and 186Re3 remained > 95% stable for up to 48 h, while 186Re7 had decreased to 7% after 3 h. LogD7.4 data of 99mTc1 - 99mTc5, 186Re1, and 186Re3 complexes, which ranged from 2.59 to 3.39, suggested high lipophilicity. Biodistribution studies in healthy Swiss albino mice showed hepatobiliary excretion for 99mTc1, 99mTc2, and 99mTc4, fast blood clearance for 99mTc4, while high liver uptake and retention for 99mTc3 and 99mTc5 were measured. Moreover, 99mTc2 showed high accumulation in the lungs with sustained retention (52.80% ID/g at 4 h p.i.) and significant brain uptake at 2 min p.i. (1.89% ID/g). The study showed the great influence of monodentate ligand in the synthesis and biodistribution of the mixed ligand complexes.

Comparative Study of a Series of 99mTc(CO)3 Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection.

Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to 99mTc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of lymph node macrophages. The current study aimed to synthesize, characterize, and biologically evaluate a series of mannosylated dextran derivatives labeled with 99mTc for potential use in SLND. The compounds were designed to have a dextran with a molecular weight of 10-500 kDa as a backbone, S-derivatized cysteines, efficient SNO chelators, and mannose moieties for binding to mannose receptors. They were successfully synthesized, thoroughly characterized using NMR techniques, and labeled with the fac-[99mTc(CO)3]+ synthon. Labeling with high yields and radiochemical purities was achieved with all derivatives. In vivo biodistribution and imaging studies demonstrated high uptake in the first lymph node and low uptakes in the following node and confirmed the ability to visualize the SLN. Among the compounds studied, 99mTc-D75CM demonstrated the most attractive biological features, and in combination with the high radiochemical yield and stability of the compound, its further evaluation as a new radiopharmaceutical for sentinel lymph node detection was justified.

Preclinical Evaluation of Novel 64Cu-Labeled Gastrin-Releasing Peptide Receptor Bioconjugates for PET Imaging of Prostate Cancer.

We report herein the preclinical evaluation of new [64Cu]Cu-gastrin-releasing peptide receptor (GRPR)-targeting tracers, employing the potent peptide antagonist DPhe-Gln-Trp-Ala-VaI-Gly-His-Sta-Leu-NH2 conjugated to NOTA (in 1) or NODAGA (in 2) chelators via a 6-aminohexanoic acid linker. The Cu-1/2 metalated peptides were synthesized by reacting 1/2 with CuCl2 and were characterized by LC-ESI-MS and HR-ESI-MS. Cu-1/2 exhibited high GRPR-binding affinities with IC50 values <3 nM, as measured in a competition assay using the GRPR-expressing human PC-3 prostate cancer cell line and [125I]I-Tyr4-BBN as the competing ligand. Tracers [64Cu]Cu-1/2 were prepared in quantitative radiochemical yield (by radio-HPLC), and their identities were confirmed by coelution with their Cu-1/2 standards via comparative HPLC studies. Lipophilicity was measured in 1-octanol/PBS (pH 7.4), and the negative log D7.4 values (≤-1) confirmed the anticipated hydrophilic character for [64Cu]Cu-1/2. Both tracers demonstrated excellent in vitro stability, with ≥98% remaining intact through 24 h at physiological conditions (PBS, pH 7.4, 37 °C). Biodistribution in PC-3 tumor-bearing mice demonstrated good tumor uptake (%ID/g at 4 h: 4.34 ± 0.71 for [64Cu]Cu-1, 3.92 ± 1.03 for [64Cu]Cu-2) and rapid renal clearance (≥87% ID at 4 h). Tumor uptake was receptor-mediated, as verified by parallel GRPR-blocking studies. Small-animal PET/CT imaging studies validated the biodistribution data. These preclinical data support that the [64Cu]Cu-1/2 tracers show promise for further development as diagnostic PET imaging agents of GRPR-expressing tumors.

Synthesis, characterization and evaluation of 68Ga labelled monomeric and dimeric quinazoline derivatives of the HBED-CC chelator targeting the epidermal growth factor receptor.

Tyrosine kinase (TK) receptors including epidermal growth factor receptors (EGFRs) are known to be overexpressed in a wide variety of solid tumors associated with poor prognosis. The HBED-CC chelator N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid 1 was coupled via one or both its propionic acid moieties with the quinazoline EGFR-TK inhibiting pharmacophore 4-amino-N-(4-((3-bromophenyl)amino)quinazolin-6-yl)butanamide 3 resulting in either a monomeric 4 or a dimeric 5 species. Ligands 4 and 5 reacted with Ga3+ generating the corresponding complexes Ga4 and Ga5. Both ligands and complexes were characterized with mass spectrometry and NMR spectroscopy and evaluated in vitro with MTT assays in A431 cells, where they showed IC50 values in the range 51.6 to 68.8 µM. Labeling of ligands 4 and 5 with the PET radionuclide 68Ga was quantitative and resulted in tracers [68Ga]Ga4 and [68Ga]Ga5 with radiochemical purities greater than 98%, which were also characterised by comparative RP-HPLC studies with Ga4 and Ga5 respectively. Radiotracers [68Ga]Ga4 and [68Ga]Ga5 were stable (intact tracer over 98%) in the reaction mixture (120 min) and in human serum (30 min). Both tracers were evaluated in vivo with biodistribution experiments in SCID mice bearing A431 tumors presenting tumor uptake of 1.34 for [68Ga]Ga4 and 1.01 %ID/g for [68Ga]Ga5 at 5 min, which was slightly decreased at 60 min p.i. and then remained stable until 120 min p.i. To the best of our knowledge, this is the first report of monomeric and dimeric quinazoline conjugates with the chelator HBED-CC, which can serve as a basis for further development of EGFR-TKI targeting tracers.

Remarkable Brain Penetration of Cyclopentadienyl M(CO)3+ (M = 99mTc, Re) Derivatives of Benzothiazole and Benzimidazole Paves the Way for Their Application as Diagnostic, with Single-Photon-Emission Computed Tomography (SPECT), and Therapeutic Agents for Alzheimer's Disease.

The synthesis and evaluation of three novel 99mTc complexes (99mTc-1-3) and their corresponding Re complexes (Re-1-3), in which the phenyl ring of 2-phenylbenzothiazole or 2-phenylbenzimidazole is replaced by the cyclopentadienyl tricarbonyl [Cp99mTc(CO)3] core, are reported. Both 99mTc and Re complexes were prepared from the corresponding ferrocenyl derivatives, and the Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography. The complexes exhibit effective in vitro binding to ß-amyloid (Aß) plaques and fibrils, inhibit Aß fibril formation, and significantly reduce Aß-induced cytotoxicity and reactive oxygen species production in neuronal cell cultures. The brain uptake of the 99mTc complexes ranges between 7.94 and 3.99% ID/g at 2 min p.i., being the highest recorded for potential 99mTc Aß plaque imaging probes in mice. Powered by their high brain uptake, the complexes represent strong theranostic candidates against Alzheimer's disease combining single-photon-emission computed tomography diagnostic (99mTc complexes) and antiamyloid therapeutic (Re complexes) potential.

Dicarbonyl cis-[M(CO)2(N,O)(C)(P)] (M = Re, 99mTc) Complexes with a New [2 + 1 + 1] Donor Atom Combination.

The synthesis and characterization of the dicarbonyl mixed ligand cis-[Re(CO)2(quin)(cisc)(PPh3)] complex, 4, where quin is the deprotonated quinaldic acid, cisc is cyclohexyl isocyanide, and PPh3 is triphenylphosphine, is presented. The synthesis of 4 proceeds in three steps. In the first, the intermediate fac-[Re(CO)3(quin)(H2O)] aqua complex 2 is generated from the fac-[NEt4]2[Re(CO)3Br3] precursor, together with the brominated products fac-[Re(CO)3(quinH)(Br)] 1a and fac-[NEt4][Re(CO)3(quin)(Br)] 1b, in low yield. In the following step, replacement of the aqua ligand of complex 2 by the monodentate isocyanide ligand leads to the formation of fac-[Re(CO)3(quin)(cisc)], 3. In the third step replacement of the species trans to the isocyanide carbonyl group of 3 by a phosphine generates complex 4. The Re complexes 2-4 were prepared in high yield and fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography. At the technetium-99m (99mTc) tracer level, the analogous complexes 3' and 4' were produced in high radiochemical purity, characterized by comparative reverse phase high-performance liquid chromatography and showed high resistance to transchelation by histidine or cysteine. This new [N,O][C][P] donor atom combination with the cis-[M(CO)2]+ core (M = Re, 99mTc) is a promising scaffold for the development of novel diagnostic and therapeutic targeted radiopharmaceuticals.

Synthesis and evaluation of 99mTc/Re-tricarbonyl complexes of the triphenylphosphonium cation for mitochondrial targeting.

INTRODUCTION: Lipophilic delocalized cations accumulate in tumor cell mitochondria due to their higher transmembrane potential. In this work, this strategy was adopted for the development of 99mTc tumor-targeted imaging agents. METHODS: Two tridentate ligands containing the triphenylphosphonium cation, L1 (S-cysteinyl) and L2 (N-iminodiacetate) as well as the respective 99mTc/ReL1 and 99mTc/ReL2 tricarbonyl complexes were synthesized. The effect of the ligands and the Re complexes on cell growth in U-87 MG glioblastoma cells was assessed. In vitro stability studies and measurement of logP of the 99mTc tracers was performed. The cellular and mitochondrial uptake of the 99mTc tracers in U-87 MG cells was evaluated. Biodistribution of 99mTcL1 and 99mTcL2 were performed on SCID mice bearing U-87 MG tumors. RESULTS: The ligands L1, L2 and the Re1 and ReL2 complexes were characterized spectroscopically. Single products 99mTcL1 and 99mTcL2, >90% stable in rat serum, were obtained. LogP was 0.40±0.14 for 99mTcL1 and -0.02±0.07 for 99mTcL2. L1, ReL1 and ReL2 caused no notable cytotoxicity and L2 was found to infer 40% inhibition of cellular growth at 10-5M as well as 80% cell death in culture at 10-4M. The cell uptake of 99mTcL1 and 99mTcL2 over 4h was 1.26±0.08% and 0.06±0.01% respectively, of which 13.41±3.63% and 18.61±6.19% was distributed in the mitochondria respectively. The initial tumor uptake in mice was found to be >1% ID/g for both 99mTc tracers. CONCLUSIONS: In vitro mitochondrial and in vivo tumor targeting was observed, better in 99mTcL1, however these properties should be optimized in future studies. Advances in Knowledge and Implications for Patient Care: Continuous efforts in this direction may lead to a suitable mitochondrial-targeted 99mTc imaging agent for tumor detection.

2-(4'-Aminophenyl)benzothiazole Labeled with 99mTc-Cyclopentadienyl for Imaging ß-Amyloid Plaques.

The development of a 99mTc-radiotracer for imaging of ß-amyloid (Aß) plaques with single photon emission computed tomography (SPECT) is strongly anticipated to provide a low cost and broadly accessible diagnostic tool for Alzheimer's disease (AD). Within this framework, 2-(4'-aminophenyl)benzothiazole, known to display affinity and specificity for Aß plaques, has been joined to the tricarbonyl fac-[M(CO)3]+ (M = Re(I), 99mTc(I)) core through the cyclopentadienyl moiety to yield stable, neutral, and lipophilic complexes (Re-1 and 99mTc-1, respectively). The Re-1 complex was completely characterized with spectroscopic methods and was shown to selectively stain Aß plaques on sections of human AD brain tissue. The 99mTc-1 complex displayed satisfactory initial brain uptake (0.53% ID/g at 2 min) and in vivo stability in healthy mice, while in transgenic 5xFAD mice, models for AD, a notable retention in the brain was noted (1.94% ID/g at 90 min). The results are encouraging and contribute to the effort of developing a SPECT amyloid imaging agent.

Rhenium(I) Tricarbonyl Complexes with (2-Hydroxyphenyl)diphenylphosphine as PO Bidentate Ligand.

In the present work, we investigated potential means to obtain neutral tricarbonyl mixed-ligand fac-[M(CO)3L1L2] complexes (M = Re, 99mTc) containing the (2-hydroxyphenyl)diphenylphosphine (POH) bidentate ligand (L1H) and a series of monodentate ligands (L2). First, fac-[Re(CO)3(PO)(H2O)], 1, was synthesized by reaction of POH and [Et4N]2[Re(CO)3Br3] 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)3L1L2] 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 99mTc-tracer level in quantitative yields after reaction of POH and the respective monodentate ligand L2 with fac-[99mTc(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 99mTc complexes during histidine and cysteine challenge assays underscored the suitability of the fac-[M(CO)3(PO)L2] system for radiopharmaceutical development purposes.

λ-Eye: a high-sensitivity γ imaging probe for axillary sentinel lymph node mapping.

OBJECTIVE: The aim of this study is the construction and performance evaluation of 'λ-eye', a γ imaging probe, optimized in terms of sensitivity for sentinel lymph node mapping. The optimization of the probe is based on theoretical models and simulation results that were presented in a previous study of our group. In this work, the construction of the probe, the experimental confirmation of the simulation results, and the evaluation of its performance with phantoms and lymph node imaging in small animals are presented. METHODS: The system's spatial and energy resolution, sensitivity, and count rate performance were measured using phantoms. The values of the integral and differential uniformity in the useful field-of-view and in the central field-of-view were also calculated. Finally, a proof-of-concept animal experiment was conducted for the imaging of the lymph nodes of normal mice. RESULTS: The system's energy resolution was measured as 36±2% and the spatial resolution was 2.2 mm at 2 mm source-collimator distance. The values of the integral uniformity and differential uniformity in the useful field-of-view and in the central field-of-view were found to be 5.2, 2.1, 1.7, and 0.75%, respectively. Finally, the lymph nodes of normal mice were clearly imaged with a 10 s acquisition time. CONCLUSION: The 'λ-eye', used for sentinel lymph node mapping, provides a combination of high sensitivity (∼1.5 counts/s/kBq) and good spatial resolution (∼6 mm full-width of the half-maximum at 20 mm and ∼10 mm full-width of the half-maximum at 50 mm distance). Its compact size (40 mm×40 mm×70 mm) allows its use during surgery and/or for the detailed scan of a suspicious region.

Crystal structure of fac-tricarbon-yl(quinoline-2-carboxyl-ato-κ(2) N,O)(tri-phenyl-arsane-κAs)rhenium(I).

In the title compound, [Re(C10H6NO2)(CO)3{As(C6H5)3}], the coordination environment of Re(I) is that of a distorted octa-hedron. Three coordination sites are occupied by three carbonyl groups in a facial arrangement and the remaining three sites by tri-phenyl-arsane and deprotonated quinaldic acid in As-mono- and N,O-bidentate fashions, respectively. In the crystal, the complexes are linked through weak C-H⋯O hydrogen bonds, forming a three-dimensional network. It worth noting that, as far as we know, this complex is the first Re(I) tri-phenyl-arsane tricarbonyl compound to be reported.